Female Urology, Urogynecology, and Voiding Dysfunction - PDF Free Download (2024)

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Female Urology, Urogynecology, and Voiding Dysfunction

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Female Urology, Urogynecology, and Voiding Dysfunction Edited By

Sandip P. Vasavada, M.D. Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A

Rodney A. Appell, M.D. Baylor College of Medicine, Houston, Texas, U.S.A.

Peter K. Sand, M.D. Northwestern University, Evanston, Illinois, U.S.A.

Shlomo Raz, M.D. David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.

Marcel dekker

New York



Although great care has been taken to provide accurate and current information, neither the author(s) nor the publisher, nor anyone else associated with this publication, shall be liable for any loss, damage, or liability directly or indirectly caused or alleged to be caused by this book. The material contained herein is not intended to provide specific advice or recommendations for any specific situation. Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress. ISBN: 0-8247-5426-3 This book is printed on acid-free paper. Headquarters Marcel Dekker, 270 Madison Avenue, New York, NY 10016, U.S.A. tel: 212-696-9000; fax: 212-685-4540 Distribution and Customer Service Marcel Dekker, Cimarron Road, Monticello, New York 12701, U.S.A. tel: 800-228-1160; fax: 845-796-1772 World Wide Web http://www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright # 2005 by Marcel Dekker. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA





There has been a convergence of the sub-specialties of female urology and urogynecology over the last several years. This development has resulted in improved care for women, as we have had to “escalate” our own knowledge and abilities. Recently, we have even seen fellowship training transcend towards this multidisciplinary goal by the creation of joint accredited fellowship programs in female urology and urogynecology. These programs have as their primary aim to create the thought leaders of tomorrow in women’s health by creating a unique group of physicians who see the “whole” patient and can treat them accordingly. It is evident that there is a strong need for more subspecialization in the field with the aging population and prevalence of incontinence and pelvic floor disorders that is present worldwide. This book speaks to the combined nature of our practices that has emanated from this approach. We have sought to have some of the top thought leaders and experts from around the world to contribute to this publication. Furthermore, these authors embody some of the exact principles, which establish our sub-specialties as being progressive and forward thinking in their approaches to the various disease processes and disorder that we treat. One of the prevailing undertones of our book speaks to the fact that there are many ways in which to treat any single disorder. We have, therefore, had several chapters written by physicians or subspecialists who may do things differently to present contradictory views. The purpose is more than to be controversial, but rather to give an entrance point for those wishing to advance the field and aim for the utopian dream of literal cures for incontinence and other women’s disorders. We all have much to learn in this area of urinary incontinence and pelvic floor disorders. It is our hope that this book will help to build on the currently existing framework and provide a platform towards better understanding of the disease processes that affect so many of our patients. Sandip P. Vasavada, Rodney A. Appell, Peter K. Sand, Shlomo Raz,

M.D. M.D. M.D. M.D.



Times have changed and so should our intellectual basis for the management of diseases and conditions. Once thought of as an anatomic structure containing disparate and unrelated viscera, the human pelvis is now appreciated as a functional syncytium as complex as any within the human body. The dysfunctions of urinary, genital, and gastrointestinal elements which constitute this complex functional–anatomic arrangement require comprehensive and inclusive management strategies. None of us is capable of mastering the vagaries of function and structure of all the elements of the human pelvis and therefore it is requisite that expertise be drawn from collaborative fields of endeavor so that as complete a management schema as is possible be developed. Additionally, the very real superimposition of behavioral, vascular and neurologic dysfunctions further make the inclusive “team” approach concept a mandatory one. This textbook represents a superb example of the inclusive approach for management. The interaction between colorectal (and gastroenterologic), urogynecologic, and urologic specialists can and does produce the best possible outcome for individual patients as well as for entire populations of individuals. The concept of pelvic medicine remains not only viable, but one that reflects the aforementioned global interaction and collaboration of similarly motivated specialists whose primary concern is the attainment of the best outcome possible for women severely afflicted by conditions which are disruptive and destructive to quality of life and, in some cases, to well being and life expectancy. This book should be viewed in the context of intellectual instruction and exchange which will make the pelvic medicine endeavor that much more successful from both the patient and medical standpoint. The editors of the authors of the text represent the best and their achievement should serve as a model for subsequent efforts in cross specialty collaboration and, possibly more importantly, harmony. Roger Dmochowski, M.D., F.A.C.S. Department of Urology Vanderbilt University Medical Center Nashville, Tennessee, U.S.A.



Over the last 10 years, all of you who care for women in your practice have been impressed with the increasing call to provide services for urinary incontinence and pelvic organ prolapse. These pelvic floor disorders are becoming more prevalent within our practices as the number of women in the age groups most affected by these disorders increases. Also, women now coming into these age groups have a more proactive approach to their own health care than did their mothers and their sophistication and expectations demand optimal care. It is estimated that the demand for pelvic floor disorders care will double in the next 25 years. This increasing demand combined with the remarkable growth in high quality research is both encouraging and intimidating. Intimidating in that as we learn more, we realize how much more we have to learn and encouraging as we watch great strides in both basic science and outcomes research take hold. This text embraces one of the fundamental concepts that leaders within both female urology and urogynecology have come to understand—that women with pelvic floor disorders are best served by an approach that acknowledges the wisdom and experience of both of these developing subspecialties. Thus, these varied accounts by divergent authors give the reader the opportunity to consider these issues from many points of view. This will inevitably lead to a richness of understanding that a single doctrine could not provide. As we face the challenge of training our residents, fellows and colleagues, we will come to appreciate this text as an excellent resource and frequent reference. These in depth discussions of both basic and complex components of Female Urology, Urogynecology and Voiding Dysfunction offer us an opportunity to both reflect and to look forward. As all involved in research and providing care in this growing field combine forces, the wisdom and philosophy embodied in this work will enable us to expand the foundation of physicians able to join in the process toward the ultimate goal of improving the quality of the care that these women receive. Karl M. Luber, M.D. University of California, San Diego Southern California Permanente Medical Group San Diego, California, U.S.A.





Preface Introduction Introduction Contributors

Roger Dmochowski Karl M. Luber

iii v vii xv

Basic Concepts 1.

Anatomy of Pelvic Support Nirit Rosenblum, Karyn S. Eilber, Larissa V. Rodrı´guez, and Shlomo Raz



Neurophysiology of Micturition Gamal M. Ghoniem and John C. Hairston



Epidemiology of Female Urinary Incontinence Christopher Saigal and Mark S. Litwin



Quality-of-Life Issues in Incontinence David F. Penson and Mark S. Litwin



Female Sexual Dysfunction Kathleen E. Walsh and Jennifer R. Berman



Hormonal Influence on the Lower Urinary Tract Dudley Robinson and Linda Cardozo



Obstetric Issues and the Female Pelvis Roger P. Goldberg and Peter K. Sand


SECTION I. INCONTINENCE Evaluation of Incontinence 8.

History and Physical Examination in Pelvic Floor Disorders Sanjay Gandhi and Peter K. Sand


Urodynamic Assessment 9.

Urodynamic Assessment: Urethral Pressure Profilometry and PTR

141 ix



Stacey J. Wallach and Donald R. Ostergard 10.

Leak Point Pressures Shahar Madjar and Rodney A. Appell



Videourodynamics Jennifer Gruenenfelder and Edward J. McGuire



Pharmacologic and Surgical Management of Detrusor Instability H. Henry Lai, Michael Gross, Timothy B. Boone, and Rodney A. Appell


Management of Urinary Incontinence 13.

Pharmacologic Management of Urinary Incontinence Alan J. Wein and Eric S. Rovner



Behavioral Treatments Diane K. Newman



Pessaries and vagin*l Devices for Stress Incontinence G. Willy Davila and Minda Neimark



Current Role of Transvagin*l Needle Suspensions Firouz Daneshgari



Anterior vagin*l Wall Suspension Tracey Small Wilson and Philippe E. Zimmern



Retropubic Urethropexy Jeffrey L. Cornella



Laparoscopic Treatment of Urinary Stress Incontinence Thomas L. Lyons



Insertion of Artificial Urinary Sphincter in Women H. Roger Hadley



Urethral Injectables in the Management of SUI and Hypermobility Sender Herschorn and Adonis Hijaz


vagin*l Sling Surgery: Overview and history 22.

vagin*l Sling Surgery: Overview, History, and Sling Material Keith J. O’Reilly and Kathleen C. Kobashi


vagin*l Sling Surgery: Techniques 23.

Use of Cadaveric Fascia Lata Allograft for Pubovagin*l Slings Matthew B. Gretzer and E. James Wright



Autologous Fascia Lata Sling Cystourethropexy Karl J. Kreder



The In Situ Anterior vagin*l Wall Sling Howard B. Goldman



CATS: Cadaveric Transvagin*l Sling




Dawn M. Bodell and Gary E. Leach 27.

Tension-Free vagin*l Tape: An Innovative, Minimally Invasive Pubovagin*l Sling for Female Stress Urinary Incontinence Vincent R. Lucente and Marisa A. Mastropietro


Distal Urethral Polypropylene Sling Larissa V. Rodrı´guez


Transvagin*l Cooper’s Ligament Sling for the Treatment of Stress Urinary Incontinence and Low-Pressure Urethra Sanjay Gandhi and Peter K. Sand

399 417



Management of Postoperative Detrusor Instability and Voiding Dysfunction Peter O. Kwong and O. Lenaine Westney



Postoperative Complications of Sling Surgery Elizabeth A. Miller and George D. Webster


Management of Refractory Detrusor Instability 32.

Detrusor Myomectomy Patrick J. Shenot


Management of Refractory Detrusor Instability: Anterior Flap Extraperitoneal Cystoplasty Eric S. Rovner, David A. Ginsberg and Shlomo Raz




Laparoscopic Enterocystoplasty Raymond R. Rackley and Joseph B. Abdelmalak



Management of Refractory Detrusor Instability: Sacral Nerve Root Stimulation Patrick J. Shenot



Physical Exam and Assessment of Pelvic Support Defects Steven Swift



Radiographic Evaluation of Pelvic Organ Prolapse Craig V. Comiter



Surgical Therapy of Uterine Prolapse Karyn Schlunt Eilber, Nirit Rosenblum, and Shlomo Raz



vagin*l Hysterectomy and Other Operations for Uterine Prolapse Paul M. Fine and Dallas Johnson



Advanced Anterior vagin*l Wall Prolapse (Stage III and IV) Christina H. Kwon and Peter K. Sand



Anterior vagin*l Wall Prolapse: Mild/Moderate Cystoceles Harriette M. Scarpero and Victor W. Nitti



Diagnosis and Treatment of the Stage IV Cystocele




Nancy B. Itano, Fernando Almeida, Larissa V. Rodrı´guez, and Shlomo Raz 43.

Surgical Correction of Paravagin*l Defects Matthew D. Barber



Paravagin*l Repair: A Laparoscopic Approach John R. Miklos, Robert Moore, and Neeraj Kohli



Transvagin*l Levator Myorraphy for vagin*l Vault Prolapse Gary E. Lemack and Philippe E. Zimmern



Sacrospinous Ligament Suspension for vagin*l Vault Prolapse Roger P. Goldberg and Peter K. Sand



Surgical Treatment of vagin*l Apex Prolapse: Transvagin*l Approaches Mark D. Walters and Tristi W. Muir



Abdominal Sacrocolpopexy for the Correction of vagin*l Vault Prolapse J. Christian Winters, Richard Vanlangendonck, and R. Duane Cespedes



Laparascopic Abdominal Sacral Colpopexy Marie Fidela R. Paraiso



Colpocleisis for the Treatment of Severe vagin*l Vault Prolapse R. Duane Cespedes and J. Christian Winters



Rectocele Repair/Posterior Colporrhaphy Nirit Rosenblum, Karyn S. Eilber, and Larissa V. Rodriguez



Evaluation and Management of Rectoceles Jeffrey L. Segal and Mickey M. Karram



Vesicovagin*l Fistula: Complex Fistulae Karyn Schlunt Eilber, Nirit Rosenblum, and Larissa V. Rodrı´guez



Vesicovagin*l Fistula: Abdominal Approach Martin B. Richman and Howard B. Goldman



Urethrovagin*l Fistula John B. Gebhart and Raymond A. Lee



Female Urethral Diverticula Sandip P. Vasavada and Raymond R. Rackley



Urethral Reconstruction in Women Jerry G. Blaivas and Adam J. Flisser



Radical Cystectomy and Orthotopic Neobladder Substitution in the Female David A. Ginsberg and John P. Stein



Interstitial Cystitis Marie-Blanche Tchetgen, Raymond R. Rackley, and Joseph B. Abdelmalak





Chronic Pelvic Pain in Interstitial Cystitis James Chivian Lukban and Kristene E. Whitmore



Fecal Incontinence Tracy Hull





Joseph B. Abdelmalak Fernando Almeida*

Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.

University of California, Los Angeles, California, U.S.A.

Rodney A. Appell, M.D. Head, Section of Female Urology and Voiding Dysfunction, F. Brantley Scott Chair. Professor of Urology and Gyneocology, Baylor College of Medicine, Houston, Texas, U.S.A. Matthew D. Barber, M.D., M.H.S. Section of Urogynecology, Pelvic Reconstruction Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Jennifer R. Berman Female Sexual Medicine Center, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Jerry G. Blaivas Joan and Sanford Weil College of Medicine, Cornell University, New York, New York, U.S.A. Dawn M. Bodell U.S.A.

Fellow, Tower Urology Institute for Continence, Los Angeles, California,

Timothy B. Boone, M.D., Ph.D. Professor and Chairman, Scott Department of Urology, Baylor College of Medicine, Houston, Texas, U.S.A. Linda Cardozo, M.D., F.R.C.O.G. Professor of Urogynaecology, Department of Obstetrics and Gynaecology, King’s College Hospital, London, England R. Duane Cespedes, M.D. Chairman, Department of Urology, Wilford Hall Medical Center, Lackland AFB, Texas, U.S.A.

*Current affiliation: Senior Associate Consultant, Department of Urology, Mayo Clinic Scottsdale, Scottsdale, Arizona, U.S.A. xv



University of Arizona Health Sciences Center, Tucson, Arizona, U.S.A.

Craig V. Comiter Jeffrey L. Cornella

Mayo Clinic Scottsdale, Scottsdale, Arizona, U.S.A.

Firouz Daneshgari Director, Center for Female Pelvic Medicine and Reconstructive Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. G. Willy Davila

Cleveland Clinic Florida, Weston, Florida, U.S.A.

Karyn Schlunt Eilber, M.D. † California, U.S.A. Paul M. Fine

Department of Urology, University of California, Los Angeles,

Baylor College of Medicine, Houston, Texas, U.S.A.

Adam J. Flisser Joan and Sanford Weil College of Medicine, Cornell University, New York, New York, U.S.A. Sanjay Gandhi, M.D. Research Fellow, Department of Obstetrics and Gynecology, Northwestern University, Evanston, Illinois, U.S.A. John B. Gebhart U.S.A.

Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota,

Gamal M. Ghoniem, M.D., F.A.C.S. Head, Section of Voiding Dysfunction and Female Urology, Cleveland Clinic Florida and the Cleveland Clinic Foundation Health Sciences Center of OSU, Weston, Florida, U.S.A. David A. Ginsberg Assistant Professor of Urology, Department of Urology, University of Southern California School of Medicine, Los Angeles, California, U.S.A. Roger P. Goldberg, M.D., M.P.H. Director of Urogynecology Research, Evanston Continence Center, Northwestern University Medical School, Evanston, Illinois, U.S.A. Howard B. Goldman, M.D. Assistant Professor of Urology, Department of Urology and Reproductive Biology, University Hospitals of Cleveland, CASE School of Medicine, Cleveland, Ohio, U.S.A. Matthew B. Gretzer

The Johns Hopkins Medical Institutions, Baltimore, Maryland, U.S.A.

Michael Gross Fellow in Neurourology, Scott Department of Urology, Baylor College of Medicine, Houston, Texas, U.S.A. Jennifer Gruenenfelder

University of Michigan, Ann Arbor, Michigan, U.S.A.

H. Roger Hadley, M.D. Professor and Chief, Division of Urology, Loma Linda University, Loma Linda, California, U.S.A. †

Current affiliation: Assistant Attending, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A.



John C. Hairston, M.D. Assistant Professor of Urology, Division of Urology, University of Texas Medical School at Houston, Houston, Texas, U.S.A. Sender Herschorn University of Toronto and Sunnybrook and Women’s Health Sciences Centre, Toronto, Ontario, Canada Adonis Hijaz University of Toronto and Sunnybrook and Women’s Health Sciences Centre, Toronto, Ontario, Canada Tracy L. Hull, M.D. Staff Surgeon, Department of Colon and Rectal Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Nancy B. Itano § Dallas Johnson

University of California, Los Angeles, California, U.S.A. Baylor College of Medicine, Houston, Texas, U.S.A.

Mickey M. Karram, M.D. Director Urogynecology, Professor OBGYN, Department of OBGYN, Good Samaritan Hospital, Cincinnati, Ohio, U.S.A. Kathleen C. Kobashi, M.D. Co-Director, Urology and Renal Transplantation, Continence Center, Virginia Mason Medical Center, Seattle, Washington, U.S.A. Neeraj Kohli, M.D. Associate Professor; Director, Division of Urogynecology, Brigham and Womens Hospital, Harvard University, Boston, Massachusetts, U.S.A. Karl J. Kreder, M.D. Professor and Clinical Vice Chair, Department of Urology, University of Iowa, Iowa City, Iowa, U.S.A. Christina H. Kwon Illinois, USA

Evanston Continence Center, Northwestern University, Evanston,

Peter O. Kwong, M.D. Fellow in Female Urology and Urinary Tract Reconstruction, Department of Surgery=Urology, University of Texas Health Science Center, Houston, Texas, U.S.A. H. Henry Lai, M.D. Resident, Scott Department of Urology, Baylor College of Medicine, Houston, Texas, U.S.A. Gary E. Leach U.S.A. Raymond A. Lee U.S.A.

Director, Tower Urology Institute for Continence, Los Angeles, Califonia,

Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota,

Gary E. Lemack, M.D. Associate Professor of Urology, Southwestern Medical Center, University of Texas, Dallas, Texas, U.S.A. §

Current affiliation: Senior Associate Consultant, Department of Urology, Mayo Clinic Scottsdale, Scottsdale, Arizona, U.S.A.



Mark S. Litwin, M.D., M.P.H. Professor, Department of Urology, David Geffen School of Medicine at UCLA and UCLA School of Public Health, Los Angeles, California, U.S.A. Vincent R. Lucente, M.D., M.B.A. } Hershey, Pennsylvania, U.S.A.

Pennsylvania State University, College of Medicine,

Urogynerology Associates of Colorado, Denver, Colorado, U.S.A.

James Chivian Lukban

Thomas L. Lyons, M.S., M.D. Atlanta, Georgia, U.S.A.

Director, Center for Women’s Care and Reproductive Surgery,

Shahar Madjar Northern Michigan Urology at Bell, Bell Memorial Hospital, Marquette County, Michigan, U.S.A. Marisa A. Mastropietro, M.D.**

University of Michigan, Ann Arbor, Michigan, U.S.A.

Edward J. McGuire John R. Miklos, M.D. Georgia, U.S.A. Elizabeth A. Miller

Lehigh Valley Hospital, Allentown, Pennsylvania, U.S.A.

Director Urogynecology, Atlanta Urogynecology Associates, Atlanta,

Duke University Medical Center, Durham, North Carolina, U.S.A.

Robert D. Moore, D.O. Assistant Director Urogynecology, Atlanta Urogynecology Associates, Atlanta, Georgia, U.S.A. Tristi W. Muir, M.D. Assistant Chief, Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Brooke Army Medical Center, Fort Sam Houston, Texas, U.S.A. Cleveland Clinic Florida, Weston, Florida, U.S.A.

Minda Neimark Diane K. Newman Victor W. Nitti

University of Pennsylvania Medical Center, Philadelphia, U.S.A.

New York University School of Medicine, New York, U.S.A.

Keith J. O’Reilly ††

Tripler Army Medical Center, Honolulu, Hawaii, U.S.A.

Donald R. Ostergard, M.D. University of California, Irvine, and Long Beach Memorial Medical Center, Long Beach, California, U.S.A. Marie Fidela R. Paraiso


Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.

Current affiliation: Medical Director, Institute for Female Pelvic Medicine and Reconstructive Surgery, Allentown, Pennsylvania, U.S.A. **Current affiliation: Director of Gynecologic Services, Lincoln Hospital, Bronx, New York, U.S.A. †† Current affiliation: Department of Urology, Madigan Army Hospital, Tacoma, Washington, U.S.A.



David F. Penson, M.D., M.P.H. §§ Section of Urology, 112-UR, University of Washington School of Medicine, VA Puget Sound HCS, Seattle, Washington, U.S.A. Shlomo Raz, M.D. Professor, Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Raymond R. Rackley, M.D. Co-Head, Section of Female Urology, Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Martin B. Richman, M.D. Department of Urology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland, Ohio, U.S.A. Dudley Robinson, M.D., M.R.C.O.G. Sub-speciality Trainee—Urogynaecology, Department of Obstetrics and Gynaecology, King’s College Hospital, London, England Larissa V. Rodrı´guez, M.D. Assistant Professor, Co-director of Division of Female Urology, Reconstructive Surgery and Urodynamics, Department of Urology, University of California, Los Angeles, California, U.S.A. Nirit Rosenblum, M.D. }} California, U.S.A.

Department of Urology, University of California, Los Angeles,

Eric S. Rovner Assistant Professor Urology, Department of Surgery, Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A. Christopher Saigal, M.D., M.P.H. Assistant Professor, Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Peter K. Sand, M.D. Professor, Department of Obstetrics and Gynecology, Evanston Continence Center, Northwestern University, Evanston, Illinois, U.S.A. Harriette M. Scarpero

New York University School of Medicine, New York, U.S.A.

Jeffrey L. Segal, M.D. Clinical Instructor OBGYN, Fellow Urogynecology, Department of OBGYN, Good Samaritan Hospital, Cincinnati, Ohio, U.S.A. Patrick J. Shenot

Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.

John P. Stein Department of Urology, University of Southern California, Los Angeles, California, U.S.A. Steven Swift, M.D. Associate Professor, Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, U.S.A.


Current affiliation: Associate Professor Urology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, Califonia, U.S.A. }} Current affiliation: Assistant Professor, Department of Urology, NYU School of Medicine, New York, New York, U.S.A.



Marie-Blanche Tchetgen

Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.

Richard Vanlangendonck, M.D. Director of Minimally Invasive Surgery, Department of Urology, Ochsner Clinic Foundation, New Orleans, Louisiana, U.S.A. Sandip P. Vasavada, M.D. Co-Head, Section of Female Urology, Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. Stacey J. Wallach, M.D.*** University of California, Irvine, and Long Beach Memorial Medical Center, Long Beach, California, U.S.A. Kathleen E. Walsh Female Sexual Medicine Center, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A. Mark D. Walters, M.D. Head, Section of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. George D. Webster

Duke University Medical Center, Durham, North Carolina, U.S.A.

O. Lenaine Westney, M.D. Assistant Professor, Department of Surgery=Urology, University of Texas Health Science Center, Houston, Texas, U.S.A. Alan J. Wein Chair, Division of Urology, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A. Kristene E. Whitmore

Graduate Hospital, Philadelphia, Pennsylvania, U.S.A.

Tracey Small Wilson U.S.A.

University of Texas Southwestern Medical Center, Dallas, Texas,

J. Christian Winters, M.D. Director of Female Urology, Department of Urology, Ochsner Clinic Foundation, New Orleans, Louisiana, U.S.A. E. James Wright

The Johns Hopkins Medical Institutions, Baltimore, Maryland, U.S.A.

Philippe E. Zimmern, M.D. Professor of Urology, Southwestern Medical Center, University of Texas, Dallas, Texas, U.S.A.

***Current affiliation: Assistant Professor, Department of Obstetrics and Gynecology, University of California, Sacramento, California, U.S.A.

1 Anatomy of Pelvic Support Nirit Rosenblum,* Karyn S. Eilber,† Larissa V. Rodrı´guez, and Shlomo Raz University of California, Los Angeles, California, U.S.A.



Female pelvic anatomy is a complex combination of muscles, ligaments, nerves, and blood vessels that act dynamically to provide support for the urethra, bladder, uterus, and rectum. An understanding of normal mechanisms of pelvic support are essential in the evaluation of women with voiding complaints, urinary incontinence, and bowel dysfunction related to pelvic floor relaxation. Thus, the treatment of female urinary incontinence often involves recognition and treatment of concurrent pelvic pathophysiology such as cystocele, uterine prolapse, enterocele, rectocele, and perineal laxity. Identification of the various components of pelvic floor dysfunction is aided by diagnostic tools such as video urodynamics and magnetic resonance imaging of the pelvis. This chapter will focus on normal female pelvic anatomy, including the supporting structures relevant to voiding dysfunction and incontinence, as well as the pathophysiology of pelvic floor relaxation, with a description of the various components of pelvic organ prolapse. II.




Passive support of the pelvic floor is provided by the bony structures, which act as anchors for the important muscular and fascial structures comprising the pelvic floor. The pubic rami, ischial spines, and sacrum represent the anchoring points of the true bony pelvis, which is made up of pubis, ilium, ischium, sacrum, and coccyx (1). The pelvic floor is diamond-shaped with the pubic symphysis and sacrum at the anterior and posterior apices while the ischial spines serve as lateral anchors. The pelvic floor can be further subdivided into anterior and posterior compartments by drawing a line between the two ischial spines. B.


The sacrospinous ligaments span the posterior portion of the pelvic floor, from the ischial spines to the anterolateral aspect of the sacrum and coccyx. The coccygeus muscle is found between the *Current affiliation: NYU School of Medicine, New York, New York, U.S.A. † Current affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A. 1


Rosenblum et al.

ischial spines and the lateral aspect of the sacrum and coccyx, overlying the sacrospinous ligament and is an important landmark in vagin*l surgery. Above the coccygeus muscle lies the sciatic nerve and its plexus, while the pudendal nerve and vessels lie lateral (Alco*ck’s canal). Medially, the sacrospinous ligament fuses with the sacrotuberous ligament (2). Anteriorly, the tendinous arc, a curvilinear condensation of pelvic fascia arising from the obturator internus muscle, runs between the ischial spines and the lower portion of the pubic symphysis. This crucial structure provides a musculofascial origin for the majority of the anterior pelvic diaphragm, allowing its attachment to the bony pelvis. The arcus tendinous flanks the urethra and bladder neck anteriorly and rectum posteriorly, providing lateral attachment of the pelvic diaphragm and its ligaments (1). The perineal body is a tendinous structure located in the midline of the perineum between the anus and the vagin*l introitus, which provides a central point of fixation for the transverse perineal musculature (3). This anchoring site provides a second level of pelvic support to the posterior vagin*l wall and rectum, incorporating the levator ani and transverse perineal musculature as well as the external anal sphincter.



The striated musculature comprising the pelvic floor acts as a supporting structure for the visceral contents of the abdominopelvic cavity as well as a dynamic organ involved in maintenance of urinary and fecal continence. The pelvic diaphragm is composed of the levator ani and coccygeus muscles. The levator ani muscle group and its fascia provide the most critical support for the pelvic viscera, acting as the true muscular pelvic floor. The levator ani group is composed of the pubococcygeus, ischiococcygeus, and iliococcygeus, named according to their origin from the pelvic sidewall (4). This broad sheet of muscular tissue extends from the undersurface of the pubic symphysis to the pelvic surface of the ischial spines, taking origin from the tendinous arc laterally. The anterior muscle group, primarily made up of pubococcygeus (puborectalis) with its overlying endopelvic fascia, directly attaches to the bladder, urethra, vagin*, uterus, and rectum, actively contributing to visceral control (Fig. 1). This important muscular support mechanism is crucial during times of suddenly increased intraabdominal pressure (1). The posterior muscle group consists of the posterior portion of the levator ani and the coccygeus muscle. Their points of origin include the more posterior portions of the tendinous arc and the ischial spines. The two sides fuse in the midline posterior to the rectum and attach to the coccyx. This plate of horizontal musculature spans from the rectal hiatus to the coccyx and allows maintenance of the normal vagin*l and uterine axis. The upper vagin* and uterine cervix lie on this horizontal plane created by the levator plate. This posterior muscle group is active at rest and contracts further during rectus abdominis contraction, maintaining proper vagin*l axis (1). Midline apertures in the levator ani group, collectively referred to as the levator hiatus, allow passage of the urethra, vagin*, and rectum. Adjacent fascial attachments provide support to these pelvic viscera as they exit the pelvis, fashioning a “hammock” of horizontal support (5). The bladder, proximal vagin*, and rectum rest on the levator floor and become coapted against it during periods of increased intra-abdominal pressure. Resting tone of the levator muscle, as well as reflex and voluntary contraction, acts to pull the vagin* and rectum forward, thereby preventing incontinence of both urine and stool. These active mechanisms of pelvic floor support maintain both urinary and fecal continence.

Anatomy of Pelvic Support


Figure 1 Schematic diagram of the striated musculature of the pelvic floor. PR, puborectalis; PC, pubococcygeus; IC, iliococcygeus; O, obturator muscle; TA, tendinous arc of the obturator muscle.



The fascia overlying the pelvic floor musculature plays a critical role in pelvic support. The abdominal portion of the fascia is referred to as endopelvic fascia and represents a continuation of the abdominal transversalis fascia (1). The levator ani muscle is covered superiorly and inferiorly by a fascial layer (Fig. 2). The two fascial layers split at the levator hiatus to cover the pelvic organs that traverse it. The superior or intra-abdominal segment (endopelvic fascia) and the inferior or vagin*l side of the levator fascia together constitute the pubocervical fascia in the classical anatomic descriptions. This levator fascia is divided into discrete areas of specialization, depending on the associated organ it supports. The specialization of levator fascia around the urethra, the pubourethral ligament, represents a fusion of the periurethral fascia and endopelvic fascia attaching to the tendinous arc. The levator fascia associated with the bladder, the vesicopelvic ligament or fascia, represents the fusion of perivesical and endopelvic fascia attached to the tendinous arc. Such condensations of the endopelvic fascia create “ligamentous” structures that support the pelvic viscera, such as the pubourethral ligaments, urethropelvic ligaments, pubocervical fascia, and cardinal and uterosacral ligaments (Fig. 3). These represent discrete supportive structures that are part of a continuum of connective tissue surrounding the pelvic organs and serve as important surgical and physiologic landmarks. An understanding of their individual contribution to pelvic visceral support is essential in reconstructive surgery. Therefore, these four fascial structures will be discussed in detail as a basis for understanding the pathophysiology of pelvic organ prolapse.


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Figure 2 Schematic diagram of the pelvic floor, specifically the levator ani musculature and its fascial condensations. The endopelvic fascia represents the abdominal side of the levator fascia. The arcus tendineus represents the insertion of the levator muscle into the obturator muscle of the lateral pelvic side wall.


Pubourethral Ligaments

The pubourethral ligaments are a condensation of levator fascia connecting the inner surface of the inferior pubis to the midportion of the urethra. They provide support and stability to the urethra and its associated anterior vagin*l wall. These ligaments divide the urethra into proximal and distal halves; the proximal or intra-abdominal portion is responsible for passive or involuntary continence. The striated external urethral sphincter is located just distal to the pubourethral ligaments so that the midurethra becomes primarily responsible for active or

Figure 3 Schematic diagram of the levator muscle fascia viewed from the vagin*l side, with specifically named condensations which form supportive ligamentous structures for the urethra, bladder, and uterus.

Anatomy of Pelvic Support


voluntary continence. The distal one-third of urethra is simply a conduit and does not significantly change continence when damaged or resected. Weakening or detachment of the pubourethral ligament causes separation of the urethra from the inferior ramus of the pubic symphysis. This pathologic process has an unclear role in continence.


Urethropelvic Ligaments

The urethropelvic ligaments are composed of a two-layer condensation of levator fascia, which provides the most important anatomic support of the bladder neck and proximal urethra to the lateral pelvic wall (Fig. 4). The first layer is known as the periurethral fascia (vagin*l side) and is located immediately beneath the vagin*l epithelium, apparent as a glistening white layer surrounding the urethra. The second layer of the urethropelvic ligament consists of the levator fascia covering the abdominal side of the urethra (endopelvic fascia), which fuses with the periurethral fascia. The two layers attach as a unit to the tendinous arc of the obturator fascia along the pelvic sidewall (Fig. 5). These lateral fusions of the levator and periurethral fascia provide important, elastic musculofascial support to the bladder outlet, thereby maintaining passive continence in women. Voluntary or reflex contractions of the levator or obturator musculature increase the tensile forces across these ligaments, increasing outlet resistance and continence. Thus, these ligamentous structures are critically important in the surgical correction of stress incontinence.


Pubocervical Fascia (Vesicopelvic Ligament)

The pubocervical fascia is a continuous sheet of connective tissue support from pubic symphysis to cervix, including the periurethral, perivesical, and endopelvic fascia, which fuse to support the bladder to the lateral pelvic wall (Fig. 6). It is formed by the fusion of fascia from the bladder wall and anterior vagin*l wall in the region of the bladder base. It is continuous distally with the periurethral fascia and proximally with the uterine cervix and cardinal ligament complex. This fascial condensation, sometimes referred to as the vesicopelvic ligament, fuses laterally with the

Figure 4 Schematic diagram demonstrating the urethropelvic ligaments, a two-layer condensation of levator fascia which envelops the urethra and surrounding neurovascular structures and attaches to the lateral side wall.


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Figure 5 Intraoperative photograph of the urethropelvic ligament, as it attaches laterally to the tendinous arc.

endopelvic fascia, attaching to the pelvic sidewall at the tendinous arc and supporting the bladder base and anterior vagin*l wall (Fig. 7). Attenuation of this lateral bladder support results in a lateral cystocele defect (paravagin*l).



The cardinal ligaments are thick, triangular condensations of pelvic fascia that originate from the region of the greater sciatic foramen. They insert into the lateral aspects of a fascial ring encircling the uterine cervix and isthmus as well as the adjacent vagin*l wall, providing important uterine and apical vagin*l support. In addition, the cardinal ligaments are an important mechanism of support for the bladder base and can be seen extending to the perivesical fascia. It is often difficult to differentiate the two structures surgically, and sharp dissection is required. These ligaments contain numerous blood vessels branching from the hypogastrics that supply the uterus and upper vagin* (1). The cardinal ligaments fuse posteriorly with the uterosacral ligaments (sacrouterine), which stabilize the uterus, cervix, and upper vagin* posteriorly toward the sacrum. They originate from the second, third, and fourth sacral vertebrae and insert into the posterolateral aspect of the pericervical fascia and lateral vagin*l fornices (6). The fascial unit comprising cardinal ligaments, uterosacral ligaments, and pubocervical fascia spreads out posterolaterally on each side of the vagin*l apex, uterus, and cervix to the pelvis (7). The broad ligaments provide additional uterine support and are located more superiorly, covered by anterior and posterior sheets of peritoneum. They attach the lateral walls of the uterine body to the pelvic sidewall and contain the Fallopian tubes, round and ovarian ligaments, and uterine and ovarian vessels.

Anatomy of Pelvic Support


Figure 6 Schematic diagram of the vagin*l fascial condensations from the pubic symphysis to the cervix, including the periurethral fascia, perivesical fascia, and cardinal ligaments. This continuous sheet of fascial support is also known as the pubocervical fascia.

Figure 7 Schematic diagram of the vesicopelvic ligament, the fascial condensation providing lateral support to the bladder base and anterior vagin*l wall.


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Rectovagin*l Septum

The rectovagin*l septum represents a fascial extension of the peritoneal cul-de-sac between the vagin*l apex and the anterior rectal wall. This septum comprises two distinct layers, the posterior vagin*l fascia and the prerectal fascia, which fuse distally at their insertion into the perineal body. More proximally, these fascial layers fuse with the cardinal-uterosacral complex to provide support for the posterior vagin*l apex. The proximal posterior vagin* and intrapelvic rectum are supported by the pubococcygeus portion of the levator ani group, which inserts into the midline raphe between the vagin* and rectum. B.


The perineal body, a tendinous structure located between the anus and vagin* in the midline, provides a central point of musculofascial insertion. This acts as an additional level of pelvic support, which is elastic in nature, thereby allowing significant distortion and recoil during childbirth and intercourse (1). Two paired superficial transverse perineal muscles run on each side of the perineal body to the ischial tuberosities laterally, with a similar deeper pair of transverse perineal muscles found more superiorly. Voluntary contraction of these transverse perineal muscles causes lateral vagin*l compression as well as stability of the perineum during acute increases in intra-abdominal pressure. The perineum can be conceptually divided into anterior and posterior triangular compartments by drawing a line between the two ischial tuberosities. The anterior urogenital triangle in the female contains the cl*tor*s, urethra, and vagin*l vestibule in the midline. The ischiocavernosus muscles cover the cl*toral crura at their attachments to the pubis. The bulbocavernosus muscles run on each side of the vagin*l vestibule beneath the labia between the cl*tor*s and the perineal body. The anal canal is found in the center of the posterior anal triangle. The external anal sphincter is composed of two layers of fibers, the deeper layer completely encircling the anal canal and fusing with the pubococcygeus-puborectal muscles superiorly.



Disruption of the normal supporting structures of the pelvis can occur secondary to numerous processes. Congenital defects are rare and will usually present in early childhood. Iatrogenic or traumatic injury as well as heavy physical labor may cause various degrees of pelvic floor relaxation. Furthermore, nulliparous women may experience pelvic floor dysfunction related to postmenopausal tissue atrophy (8). Neuromuscular damage of the pelvic floor can be caused by chronic constipation with straining, childbirth, and pelvic organ prolapse. Such denervation injury leads to levator ani and coccygeal muscular atrophy and dysfunction, contributing to pelvic floor relaxation and urinary and fecal incontinence (9). Deficiency of pelvic support is most commonly related to childbirth or hysterectomy. Aging is associated with both loss of tissue elasticity and neuronal mass, additional factors contributing to loss of pelvic support. Genitourinary and bowel manifestations of pelvic floor relaxation do not routinely occur immediately following childbirth, but often present soon after menopause, when the hormonal milieu changes. This adds further evidence to the importance of dynamic changes in pelvic musculature and connective tissue following hormonal alterations, which contribute to loss of pelvic support. The initial symptom associated with pelvic floor dysfunction in women is usually stress urinary incontinence. However, bowel, urinary, and

Anatomy of Pelvic Support


sexual functions are all significantly affected by loss of pelvic support. Bladder outlet resistance is compromised, allowing intravesical pressures to exceed those of the urethra and bladder neck and leading to urinary incontinence. Thus, the mechanisms of maintaining bladder outlet resistance in women are an important and integral component of pelvic floor dysfunction. A.

Mechanisms of Urethral Continence in Women

Bladder outlet resistance in women is attained by several factors working together to provide continence at rest and during stress maneuvers. Urethral anatomy, including functional length and elastic closure, is an important determinant of continence. In addition, activity of the muscular pelvic floor with its associated connective-tissue elements helps to maintain outlet resistance during times of increased intra-abdominal pressure. The anatomic position of the urethra is another factor contributing to continence. Each of these entities will be discussed separately in order to provide a basis for understanding the pathophysiology of pelvic floor relaxation. B.

Urethral Length

The distance between internal meatus and external urethral meatus in a female determines anatomic length. Congenital anomalies and traumatic injuries may result in significant urethral loss with subsequent incontinence. Functional urethral length is determined by urethral pressure profilometry where the total urethral length is assessed by urethral pressure exceeding bladder pressures (10). The clinical utility of urethral length has not been consistently proven. Funneling of the bladder neck and proximal urethra during straining cystography is seen in up to 50% of continent women (11). Furthermore, surgical incision of the bladder neck and Y-V plasty do not cause incontinence in women with otherwise normal outlets. In addition, resection of the distal one-third of the urethra does not produce incontinence. However, despite these observations, a critical length of healthy urethra is necessary to provide the coaptation for passive continence and continence during increases in abdominal pressure. Bladder neck suspensions may restore functional urethral length, thereby improving continence. C.

Urethral Closure

The urethra is made up of three functional anatomic components that result in an elastic, dynamic conduit with mucosal coaptation. The urethral mucosa is a transitional epithelium with numerous infoldings that allow distensibility and closure with excellent coaptation. Beneath the mucosa is a spongy tissue made up of vascular networks analogous to the corpus spongiosum in the male. Surrounding the spongy tissue is a thin musculofascial envelope, the periurethral fascia, which appears as a glistening white membrane. These three components create a coaptive seal. Urethral closure is also affected by surrounding connective tissue structures. The pubourethral ligaments provide stability to the midurethra, especially during increases in intraabdominal pressure. In addition, the tensile forces of the urethropelvic ligaments along with the adjacent levator musculature facilitate compression of the proximal and midurethra. Finally, the striated musculature of the midurethral complex adds resting tone to the urethra, further effecting closure. Surrounding the sphincteric unit is skeletal musculature that provides an important additional mechanism for urethral closure. The striated musculature provides resting urethral tone as well as an involuntary reflex contraction in response to stress that increases coaptation. Furthermore, voluntary contraction also helps to prevent loss of urine by improving urethral closure. These mechanisms increase urethral resistance, as measured by leak point pressures, but may not directly affect urethral pressures.



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Pelvic Floor Activity During Increased Intra-Abdominal Pressure

Female continence is maintained during increases in intra-abdominal pressure by several distinct mechanisms. Abdominal pressure is passively transmitted to the proximal urethra followed by an active contraction of the striated external sphincter musculature (12). Furthermore, the suburethral supportive layer, made up of periurethral fascia, anterior vagin*l wall, and levator ani muscles, provides a firm backboard against which the urethra is compressed rapidly during increases in intra-abdominal pressure (13). Both the levator musculature and the urogenital diaphragm undergo reflex contraction, resulting in increased midurethral pressure. Furthermore, voluntary contraction of the levator and obturator muscles increases tension on the urethropelvic ligaments. These factors act in concert to promote urethral continence during changes in position and abdominal pressure.


Anatomic Position

Both the bladder neck and the urethra are normally maintained in a high retropubic position relative to the more dependent bladder base, creating a valvular effect. The bladder neck and urethra are supported by a musculofascial layer that suspends these structures from the pubic bone and pelvic sidewalls, thereby preventing their descent during increases in intra-abdominal pressures (14). A limited degree of bladder base rotation against a well-supported urethra occurs with increased abdominal pressures, further creating a valvular effect between these two structures (5). Furthermore, direct transmission of intra-abdominal forces to a well-supported proximal urethra increases its resistance and promotes coaptation (15). This complex set of compensatory mechanisms in a normal healthy woman allows maintenance of sufficient outlet resistance to promote continence, especially during episodes of abdominal stress such as coughing, sneezing, walking, and straining. Any process that results in deterioration of these mechanisms can result in incontinence. Urethral function can be compromised by atrophy of its spongy tissue secondary to menopausal hormonal deficiency, altered neuromuscular function, or intrinsic damage from surgery, radiation, or trauma. In addition, a weakening of the levator musculature impairs the compensatory increases in midurethral pressures during stress. Although these physiologic changes can adversely impact on continence, the most common etiology of impaired outlet resistance in women is the loss of anatomic support of the bladder neck and urethra. Relaxation of the pelvic floor as well as weakening of the urethropelvic ligaments and midurethral complex produces significant posterior and downward rotation of the urethra and bladder neck (Fig. 8). This anatomic repositioning of the urethra and bladder neck to a more dependent pelvic position eliminates the valvular effect. Sudden increases in intra-abdominal forces facilitate funneling and opening of a poorly supported bladder outlet. The extra-abdominal location of the poorly supported proximal urethra and the loss of the backboard of strong normal support of the urethropelvic ligaments do not allow effective transmission of abdominal forces. Although such anatomic changes can lead to incontinence, urethral hypermobility does not always correlate with incontinence. Many asymptomatic women with urethral hypermobility on physical examination do not report urinary incontinence. Thus, the anatomic position of the urethra alone does not correlate with the degree of incontinence. A component of intrinsic sphincter deficiency must be present along with these anatomic changes to create incontinence. The factors responsible for pelvic floor relaxation rarely affect isolated anatomic areas. Thus, stress urinary incontinence resulting from urethral and bladder neck hypermobility is often accompanied by associated defects of pelvic support. The identification of these concomitant defects is crucial to planning effective therapy, with restoration of pelvic support, anatomic vagin*l axis, and outlet resistance. Defects in pelvic support can be organized

Anatomy of Pelvic Support


Figure 8 Schematic diagram demonstrating weakness of the urethropelvic ligament, allowing posterior and downward rotation of the urethra.

according to their effects on various pelvic organs and structures, in order to allow a more systematic approach to treatment planning (5). The vagin*l compartment contains a confluence of urinary, genital, and bowel organs. The goal of pelvic reconstructive surgery is to restore both anatomy and function. However, the restoration of anatomy does not always correlate with restoration of function.


ANTERIOR vagin*L WALL PROLAPSE Bladder Neck and Urethra

Bladder neck hypermobility associated with stress incontinence most commonly results from attenuation of the urethropelvic ligaments or their attachment to the pelvic sidewall at the level of the tendinous arch of the obturator fascia. Furthermore, intrinsic sphincter deficiency (ISD) in addition to hypermobility gives way to incontinence. Normally, loss of anatomic position can be compensated for by the balance of forces that maintain continence: urethral length, urethral closure, and changes in urethral function that take place during episodes of stress (the valvular effect, increased urethral resistance secondary to levator contraction, and the transmission of intraabdominal forces). Failure of these compensatory mechanisms will lead to stress incontinence. Recently, more attention has been given to midurethral function as an etiologic factor in the development of stress incontinence. Normally, the bladder neck acts as the primary mechanism of continence. However, with intrinsic sphincter deficiency, the midurethral complex becomes the main compensatory mechanism maintaining continence. Much of our current armamentarium for curing stress incontinence is aimed at improving mid to distal urethral function and competence (i.e., transvagin*l tape or sling). Although it is unclear how such methods correct incontinence in this segment of the urethra, we do know that anatomy and hypermobility have not necessarily been corrected. In patients with stress incontinence and urethral hypermobility, there is rotational descent of the bladder neck and urethra under the pubic symphysis. The bladder neck funnels with Valsalva maneuvers, facilitating the loss of urine. However, the degree of rotational descent


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does not correlate with the degree of incontinence. The urethra rotates beyond the pubourethral ligament, often with separation of the midurethral complex from the inferior pubic ramus. The significance of this anatomic finding is unclear, but it is thought to play a role in midurethral function. Videourodynamic evaluation confirms separation of the midportion of the urethra from its normal attachment to the underside of the symphysis pubis as well as bladder neck and urethral hypermobility in women with stress incontinence and loss of pelvic support. Based on these findings we have altered our surgical approach in treating stress incontinence, by focusing on the midurethral complex during attempts at restoring support. Although restoration of both anatomic position and underlying support are critical in the treatment of stress incontinence, it is important to recognize that the majority of women with bladder neck hypermobility do not experience significant incontinence. Intrinsic urethral function contributes significantly to continence and may be the determining factor in compensating for loss of bladder neck and urethral support. Therefore, women with stress incontinence and bladder outlet hypermobility must have some component of intrinsic urethral dysfunction. Anatomic support alone is not sufficient to achieve continence if urethral resistance remains inadequate. B.

Intrinsic Urethral Dysfunction

The plasticity of the highly efficient mucosal seal mechanism found in the urethra allows perfect continence. Infolding and deformity of the inner mucosal layer create a seal mechanism and provide a leak-proof mechanism. Minimal extraurethral forces are necessary for continence if this inner layer is intact. The intrinsic urethral tissues are affected by trophic hormonal influences. Thus, the lack of estrogen following menopause may lead to thinning and flattening of the urethral epithelium as well as atrophy of the spongy vascular tissue, which is replaced by fibrous tissue. Additional factors, which may impair the ability of the urethra to achieve or maintain a perfect seal, include numerous surgical procedures, pelvic trauma, radiation therapy, and neurogenic disease. Incontinence related to the bladder outlet was previously categorized into anatomic incontinence, due to inadequate support of the bladder neck and urethra, and intrinsic sphincter dysfunction, due to inadequacy of urethral resistance. However, this differentiation is no longer important because we now recognize that every woman with stress incontinence has a component of ISD. Thus, surgical therapy is aimed not only at correcting the anatomical defect but also at restoring coaptation and urethral closure (16). With compromise of intrinsic urethral function, stress incontinence may result despite adequate pelvic support. Thus, simple suspension of the bladder neck or urethra will be insufficient in restoring continence, and treatment must be aimed at restoring urethral coaptation and compression as well as anatomic support. Such treatments include sling procedures, injection of urethral bulking agents, or implantation of artificial sphincter devices. C.


Loss of bladder neck and urethral support represents only one component of anterior vagin*l wall prolapse. A significant number of women with stress incontinence will also have a cystocele, which may require surgical correction as well. A cystocele is defined as descent of the bladder base below the inferior ramus of the symphysis pubis, either at rest or with straining (17). Several systems of classification are in use that grade cystoceles based on degree of descent. We utilize a system of cystocele grading that includes four degrees of anterior vagin*l wall prolapse. Grades I and II cystourethroceles are described as a mild to moderate degree of anterior vagin*l wall

Anatomy of Pelvic Support


hypermobility during straining, usually ,2 cm. As a solitary entity, these are usually asymptomatic unless associated with significant bladder neck and urethral hypermobility, leading to stress incontinence. A grade III cystourethrocele is described as descent of the bladder base and anterior vagin*l wall to the introitus during straining, while a grade IV cystourethrocele is descent of the bladder base and anterior vagin*l wall beyond the introitus at rest. These higher degrees of cystocele are more frequently symptomatic, with complaints of dyspareunia, a sensation of a painful or painless vagin*l bulge, recurrent urinary tract infections, nonspecific back pain, renal failure, and difficulty walking. Importantly, retention of urine may occur secondary to kinking at the level of the bladder neck, especially if the urethra has been fixed by previous surgery (17). Many patients will describe the need to manually reduce the cystocele in order to facilitate voiding. Silent hydroureteronephrosis can develop as a result of ureteral obstruction, often confounded by a patient’s delay in seeking treatment. Anterior vagin*l wall support defects are further categorized by location of the primary anatomic defect. Weakness or disruption of the lateral attachments of the vesicopelvic or cardinal ligaments to the pelvic sidewall, at the level of the tendinous arch of the obturator, causes lateral cystocele defects. These lateral defects account for 70 –80% of all anterior vagin*l wall prolapse (17). Central cystocele defects result from attenuation of the vesicopelvic fascia in the midline, allowing herniation of the bladder base into the vagin* (5) (Fig. 9). Isolated central cystoceles account for 5– 15% of all cystocele defects (17). Commonly, the two support defects occur in conjunction and are often found in women with high-grade prolapse, such as grade IV cystoceles (Fig. 10). Both the lateral and the central defects must be corrected at the time of surgical repair in order to restore anatomic position and prevent progression or recurrence of the cystocele defect. The anterior vagin*l wall is supported in a rectangular configuration by the cardinalsacrouterine ligament complex combined with the periurethral fascia and vesicopelvic ligaments. The superior aspect of the rectangle is the periurethral fascia, the lateral walls are the vesicopelvic ligaments, and the inferior aspect (base) is made up of the cardinal ligaments. The fibers of the pubocervical fascia fuse bilaterally with the anterior aspect of the cardinal

Figure 9 Schematic diagram of a central defect cystocele, resulting from attenuation of the vesicopelvic fascia in the midline.


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Figure 10 Intraoperative photograph of high-grade cystocele following dissection of the perivesical fascia from the overlying vagin*l wall.

ligaments. Thus, in women with good uterine support as a result of strong cardinal ligaments, the base of this rectangle will be short and centrally located. On the other hand, in cases of uterine prolapse or significant laxity of the cardinal-sacrouterine ligament complex following hysterectomy, there will be elongation and separation of the rectangular base and widening of the levator hiatus. These defects in support allow formation of a central cystocele defect (5). Thus, the first maneuver during surgical correction of a cystocele involves reapproximation of the cardinal and uterosacral ligaments to the midline, essentially narrowing the base of the rectangle to prevent further cystocele progression.


vagin*L VAULT PROLAPSE Uterus and vagin*l Vault

The most critical supporting structures of the uterus and vagin*l vault are the sacrouterine and cardinal ligament complex. Relaxation of these structures results not only in anterior vagin*l wall prolapse, but also in vault and uterine prolapse as well as enterocele formation. Uterine prolapse is described as uterine descent at rest or with straining and is further classified in a manner similar to cystocele grading, as previously described. Grade I uterine prolapse is described as minimal mobility, grade II as uterine descent to the level of the midvagin* with straining, grade III as descent to the vagin*l introitus with straining, and grade IV, or procidentia, as prolapse through the introitus. Grades I and II uterine prolapse are often asymptomatic, but when symptomatic present with back pain aggravated by standing. More severe grades of uterine

Anatomy of Pelvic Support


prolapse are associated with a vagin*l mass, pelvic pain, dyspareunia, urinary retention, and incontinence (17). Initially, weakness of the sacrouterine ligaments allows anterior movement of the cervix, compromising the position of the uterus over the horizontal levator plate. The uterine axis gradually changes, leading to retroversion with the corpus falling backward. Abdominal pressures are transmitted to the anterior surface of the uterus, causing progression of uterine prolapse (17). Following hysterectomy, deficient sacrouterine and cardinal ligamentous support may result in prolapse of the vagin*l dome and cuff. Uterine prolapse rarely occurs as an isolated defect of pelvic support and is treated either by uterine suspension procedures or by hysterectomy, with treatment of the accompanying defects in pelvic support. Vault prolapse or eversion requires fixation of the apex to the sacrum, sacrospinous ligament or ileococcygeus muscle, often in conjunction with repair of anterior and posterior vagin*l wall defects (18). B.


An enterocele is defined as a herniation of peritoneum and its contents at the level of the vagin*l apex. Enteroceles occur in the upper, posterior portion of the vagin* in association with the culde-sac of Douglas. Most enteroceles are acquired following hysterectomy, caused by separation of the cardinal-sacrouterine complex and described as a “pulsion” defect at the vagin*l dome (19). Enteroceles are classically divided into four types: Congenital enteroceles result from failure of fusion of the layers of peritoneum at the level of the rectovagin*l septum and are not associated with cystocele or rectocele. Traction enteroceles occur when prolapse of the vagin*l vault or uterus pulls the peritoneum in a caudal direction. Pulsion enteroceles form as a result of chronic pressure exerted on the vagin*l vault. This force creates a hernia sac and pushes the vagin*l vault caudally, causing a sliding herniation of the vault and anterior vagin*l wall along the surface of the rectum. Pulsion enteroceles are very rarely associated with uterine prolapse. Iatrogenic enteroceles form following a surgically induced change in the vagin*l axis, where the cul-de-sac of Douglas is left unprotected. Classically, this type of enterocele is seen after colposuspension, with an incidence of 26.7% following Burch colposuspension (17). Furthermore, enteroceles can be classified based on associated anatomic findings at the time of examination, in order to guide the course of treatment. Simple enteroceles exist without concomitant vault prolapse, and the vagin*l cuff is well supported. In addition, no cystocele or rectocele is present. Complex enteroceles are associated with vault or uterine prolapse, with poor support of the vagin*l cuff. Prolapse may include the anterior vagin*l wall (cystocele) or the posterior vagin*l wall (rectocele) (17). In patients with complex enteroceles there are two discrete defects: separation of the prerectal from the perivesical fascia, and descent of the vault due to weakness of the sacrouterine and cardinal ligaments. Both of these defects must be addressed during vault prolapse repair. In general, enteroceles are minimally symptomatic until descent reaches the level of the hymen. The patient may complain of a sensation of fullness in the perineal area or sensation of a vagin*l bulge. Dyspareunia, vagin*l discomfort, and low back pain accentuated in the upright position are also common. In rare instances, complications of bowel obstruction may be seen. Concomitant cystocele and/or rectocele may produce bowel and bladder symptoms (17). Diagnosis of an enterocele is made by physical examination, often with observation of a vagin*l mass bulging through the introitus. Bimanual rectovagin*l examination during straining may reveal an impulse of the peritoneal sac against the examining fingertip. Furthermore, thickness of the proximal rectovagin*l septum may be appreciated. Radiographic imaging can be utilized to confirm the suspected diagnosis of an enterocele. Plain film radiography may reveal bowel gas within a prolapsing mass below the pubic symphysis. A voiding cystourethrogram during


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straining will exclude the bladder as the source of a mass (17). Magnetic resonance imaging of the pelvis during both a relaxed and straining state can elucidate the presence of an enterocele. Fat, small intestine, fluid, and bowel gas can be identified within a protruding vagin*l mass well below the pubococcygeal line (20). Enterocele repair commonly involves repair of concomitant pelvic prolapse defects as well as resuspension of the vagin*l vault.



Two distinct levels of musculofascial support, the pelvic floor (the pubococcygeal portion of the levator ani musculature) and the perineum, make up the posterior vagin*l wall in addition to the prerectal and pararectal fasciae. The perineum is made up of the bulbocavernosus muscle, the superficial and deep transverse perineal muscles, the external anal sphincter, and the central tendon of the perineum (21,22) (Fig. 11). In the normal upright female, the proximal two-thirds of the vagin* is 1108 from the horizontal plane compared with the distal one-third. The transition from proximal to distal vagin* occurs at the point where the vagin* crosses the pelvic floor, influenced by the degree of support of the levator musculature and urogenital diaphragm. Thus, the proximal half of the vagin* is oriented horizontally, lying over the levator plate (Fig. 12). Levator contraction pulls the vagin* forward and increases the angulation between proximal and distal posterior vagin*. Changes in intra-abdominal pressure tend to further close and support the posterior vagin*l wall, thereby preventing prolapse. When the posterior vagin*l wall axis is altered, i.e., following bladder neck suspension, intra-abdominal

Figure 11 Schematic diagram of perineal musculature, providing support to posterior vagin*l wall and rectum.

Anatomy of Pelvic Support


Figure 12 Schematic diagram representing a sagittal view of the pelvis with a normal vagin*l axis. The proximal portion of the vagin* lies horizontally, resting on the levator plate, providing support for the uterus, rectum, and bladder base.

forces tend to push the posterior vagin*l wall forward, increasing the tendency for rectocele formation. The levator musculature and the perineal body support the distal aspect of the vagin* (17). Damage to or relaxation of the levator musculature results in widening and elongation of the levator hiatus and disappearance of the normal proximal vagin*l axis. The posterior vagin*l wall becomes flattened, and intra-abdominal forces will tend to make the posterior vagin*l wall prolapse forward (17). There are several components of posterior vagin*l wall support to take into consideration: the presence of a rectocele; separation of the levator hiatus; relaxation and widening of the introitus; and relaxation and herniation of the perineum. In addition, damage to the perineal support mechanisms results in further widening of the vagin*l introitus, with an increase in the distance between the urethra and the posterior fourchette. Perineal tears may also be present in varying degrees, the most severe form being direct continuity between the posterior vagin*l wall and underlying rectum. The result of these anatomic changes is the development of a rectocele, possibly a posterior and high enterocele and perineal laxity. The importance of the rectovagin*l septum as a supporting structure for the rectum has been emphasized by Richardson (23). Milley and Nichols described this layer of fascia after performing both surgical and cadaveric dissections. This fascial layer envelops the posterior vagin*l wall, merging into the uterosacral ligaments and adhering to the cul-de-sac peritoneum. Distally, it merges into the perineal body fusing with the fibers of the deep transverse perineal muscle. Laterally, this fascial layer fuses with the iliococcygeus and pubococcygeus muscles just below the arcus tendineus (23). The rectovagin*l septum acts to separate the rectal compartment from the urogenital compartment.



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A rectocele is described as intravagin*l herniation of the rectum through an attenuated rectovagin*l septum. In addition, defects in the prerectal and pararectal fasciae are also associated with rectocele formation. Isolated breaks in the rectovagin*l septum facilitate rectocele formation. Generally, there are several areas along the rectovagin*l septum where breaks are commonly found. The most common site is a transverse separation immediately above the attachment of this septum to the perineal body, resulting in a low rectocele (seen just inside the introitus). A midline vertical defect is equally common and most likely represents a poorly repaired or poorly healed episiotomy. Rarely, one can see lateral separation on one side (23). Symptoms of rectocele are often related to bowel function and sexual intercourse; they include a sensation of fullness in the vagin*, a mass bulging through the introitus, difficulty with rectal evacuation, constipation, the need for manual reduction to improve bowel emptying, and interference with intercourse (17). The diagnosis of a posterior vagin*l wall support defect is made by physical examination. A rectocele manifests as a bulge extending from the posterior vagin*l wall, which can be better identified by placing a half-speculum anteriorly to support the anterior vagin*l wall and bladder during straining maneuvers. Bimanual rectovagin*l examination reveals significant attenuation of the rectovagin*l septum. In addition, loss of the normal right-angle configuration between the proximal and distal vagin*l segments is exhibited. Similar to enteroceles, rectoceles can be diagnosed radiographically by the presence of bowel gas below the inferior pubic ramus on plain radiography or by magnetic resonance imaging of the pelvis during relaxed and straining conditions (Fig. 13). It is rare to find an isolated posterior wall defect, or rectocele. One must identify associated defects in pelvic floor support prior to planning surgical correction. Perineal tears are commonly seen in conjunction with severe rectoceles in multiparous women. Type I defects have an intact, but thin, perineum with a defect in the anterior muscle fibers of the external anal sphincter, the puborectalis muscle and perirectal fascia, and the transverse perineal muscles. Type II defects result in total loss of the perineal body secondary to obstetric trauma. Type III defects present with a rectovagin*l fistula in the lower rectovagin*l wall following a history of obstetric trauma. In type IV defects, a fistula is present in the bottom third of the vagin*l wall with an intact perineum. This usually results from a partially healed fourth-degree laceration during delivery. These defects in the perineum, with resultant widening of the levator hiatus, may lead to progressive loss of control of both gas and feces (24). Further discussion of external anal sphincter defects as well as perineal herniation is found in subsequent sections.


Perineal Laxity

Perineal herniation or laxity results most commonly from obstetric trauma, with attenuation of the central tendon of the perineum. The discrete anatomic defect results in an increase in the distance from the posterior fourchette to the anus as well as an outward convexity of the perineum during straining. In addition, perineal laxity contributes further to widening of the vagin*l introitus. This defect in perineal support can be seen either with or without a concomitant rectocele. Symptoms or signs specifically associated with perineal body defects can include incontinence of stool, incontinence of flatus, or severe constipation requiring perineal pressure to facilitate defecation. In general, this is a relatively rare condition and is often associated with a severe degree of posterior vagin*l wall prolapse.

Anatomy of Pelvic Support


Figure 13 Magnetic resonance imaging of the pelvis in a sagittal plane during straining. A large, dark structure is seen below the both the pubococcygeal line and puborectalis muscular sling, representing a high-grade rectocele.


Anal Sphincter

Damage to the external anal sphincter can also result from obstetric trauma, such as grade IV perineal tear involving the rectum and/or anus or injury to the central tendon of the perineum as previously mentioned. Furthermore, anal sphincter laxity or defects can be a result of neurologic injury. This defect will lead to fecal incontinence, incontinence of flatus, poor sphincter tone on physical examination, and a palpable anatomic defect in the external anal sphincter. This defect is often present when signs of perineal laxity are found in addition to high-grade pelvic prolapse. Reconstruction of the anal sphincter involves transperineal plication of the levator ani musculature and the external anal sphincter as well as reapproximation of the transverse perineal musculature to the external anal sphincter.



A complete and thorough understanding of pelvic floor anatomy provides a basis for the goals of vagin*l and pelvic reconstructive surgery. First, identification of all pelvic floor pathology and organ prolapse is necessary to plan a definitive therapeutic approach to reconstruction. Diagnostic imaging of pelvic prolapse is a useful adjunct to physical examination, specifically haste sequence magnetic resonance imaging during relaxed and strained states. Concurrent


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pelvic organ pathology, including ovarian and uterine abnormalities as well as hydronephrosis, can be identified and subsequently addressed at the time of surgical intervention. Repair of all elements of pelvic floor prolapse must be achieved with special emphasis given to restoration of vagin*l axis. The normal posterior curvature of the proximal vagin* must be restored to allow intra-abdominal forces to cause vagin*l coaptation and prevent subsequent or recurrent organ prolapse. This goal of reconstructive surgery cannot be overemphasized.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

15. 16. 17.

18. 19. 20.

Klutke CG, Siegel CL. Functional female pelvic anatomy. Urol Clin North Am 1995; 22:487– 498. De Lancey JO. Surgical anatomy of the female pelvis. In: Rock JA, Thompson JD, eds. Te Linde’s Operative Gynecology. Philadelphia: Lippincott-Raven, 1997:63 – 93. Tanagho EA. Anatomy of the lower urinary tract. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1992:40 –69. Redman JF. Surgical anatomy of the female genitourinary system. In: Buchsbaum HJ, Schmidt JD, eds. Gynecologic and Obstetric Urology. Philadelphia: W.B. Saunders, 1993:25 – 60. Raz S, Little NA, Juma S. Female urology. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1992:2782 – 2829. De Lancey JOL, Richardson AC. Anatomy of genital support. In: Hurt WG, ed. Urogynecologic Surgery. Gaithersburg, IL; Rockville, MD: Aspen Publishers, 1992:19 – 33. Baden WF, Walker T. The anatomy of uterovagin*l support. In: Baden WF, Walker T, eds. vagin*l Defects. Philadelphia: Lippincott, 1992:25 – 50. Stanton SL. vagin*l prolapse. In: Raz S, ed. Female Urology. Philadelphia: W.B. Saunders, 1983:229– 240. Strohbehn K. Normal pelvic floor anatomy. Obstet Gyn Clin North Am 1998; 25:683 –705. Bruskewitz R. Urethral pressure profile in female lower urinary tract dysfunction. In: Raz S, ed. Female Urology. Philadelphia: W.B. Saunders, 1983:112 – 122. Versi E, Cardozo LD, Studd JWW, Brincat M, O’Dowd TM, Cooper DJ. Internal urinary sphincter in maintenance of female continence. B M J 1986; 292:166 – 167. Steers WD. Physiology and pharmacology of the bladder and urethra. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1998:870 – 915. Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1998:917 – 926. Blaivas JG, Romanzi LJ, Heritz DM. Urinary incontinence: pathophysiology, evaluation, treatment overview, and nonsurgical management. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1998:1007 – 1043. Enhorning G. Simultaneous recording of intravesical and intraurethral pressure. Acta Chir Scand 1961; 276:3. Raz S, Siegel AL, Short JL, Snyder JA. vagin*l wall sling. J Urol 1989; 141:43– 46. Raz S, Stothers L, Chopra A. vagin*l reconstructive surgery for incontinence and prolapse. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 1998:1059 –1094. Raz S. The anatomy of pelvic support and stress incontinence. In: Raz S, ed. Atlas of Transvagin*l Surgery. Philadelphia: W.B. Saunders, 1992:1 –22. Zacharin RF. Pulsion enterocele: review of the functional anatomy of the pelvic floor. Obstet Gynecol 1980; 55:135 –140. Rodriguez LV, Raz S. Diagnostic imaging of pelvic floor dysfunction. Curr Opin Urol 2001; 11:423– 428.

Anatomy of Pelvic Support 21. 22.

23. 24.


Huisman AB. Aspects of the anatomy of the female urethra with special relation to urinary continence. Contrib Gynecol Obstet 1983; 10:1 – 31. Joseph J. Female genital structure and function. The bones, joints, and ligaments of the female pelvis. In: Phillip E, Barnes J, Newton M, eds. Scientific Foundations of Obstetrics and Gynecology. Chicago: Year Book, 1986:86 – 94. Richardson AC. The rectovagin*l septum revisited: its relationship to rectocele and its importance in rectocele repair. Clin Obstet Gynecol 1993; 36:976 –983. Wiskind AK, Thompson JD. Fecal incontinence and rectovagin*l fistulas. In: Rock JA, Thompson JD, eds. Te Linde’s Operative Gynecology. Philadelphia: Lippincott-Raven, 1997:1207 – 1236.

2 Neurophysiology of Micturition Gamal M. Ghoniem Cleveland Clinic Florida and the Cleveland Clinic Foundation Health Sciences Center of OSU, Weston, Florida, U.S.A.

John C. Hairston University of Texas Medical School at Houston, Houston, Texas, U.S.A.



The lower urinary tract has two essential functions: the low-pressure storage of urine in a continent reservoir, and the timely expulsion of stored urine in a coordinated, efficient, and complete fashion. These two mutually exclusive functions are ultimately determined by the activity of the smooth and striated musculature of the bladder, urethra, and external urethral sphincter under the control of various neural circuits in the brain and spinal cord. Although a result of complex interplay between both the central and peripheral nervous systems, these functions are also influenced by several anatomic factors such as integrity of the pelvic floor support and dynamic relationship of the bladder and its outlet to various points in the bony pelvis and adjacent organs during voiding. In addition, as our understanding of lower urinary tract neurophysiology grows, so grows the list of neurotransmitters and receptors identified as having a role in voiding function and dysfunction. Voiding dysfunction can occur as a result of neurologic disease or injury, disturbance of anatomical relationships within the pelvis and urinary organs, or as an unwanted, often unrecognized pharmacologic effect of medical therapy for other diseases. Voiding dysfunction also occurs as a result of normal aging and is affected by changes in the viscoelastic properties of the bladder wall. As with other neurologic systems, innervation of the lower urinary tract is not static; it changes in response to disease and aging. This phenomenon is known as neural plasticity. More often than not, the etiology of voiding dysfunction is multifactorial, so a fundamental understanding of the neuroanatomy and neurophysiologic mechanisms of the lower urinary tract is essential.




Excitation-Contraction Coupling

The process of force generation of muscle in response to ligand binding has been termed excitation-contraction coupling. It is a very complex process that results from molecular changes 23


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induced by a neurotransmitter crossing the postsynaptic cleft. The details of these intricate events are beyond the scope of this chapter and best left to a major physiology text, but the central concepts can be summarized as follows. Smooth muscle cell morphology differs from that of striated muscle in that the major contractile protein in smooth muscle is actin, whereas myosin predominates in striated muscle. Nevertheless, force is ultimately generated by interaction of these two myofilaments. Cardiac muscle and striated muscle have been studied to a much larger extent than smooth muscle, but much of what we know about smooth-muscle physiology comes from the fields of gastroenterology and obstetrics. The molecular events leading to smooth-muscle contraction are shown in Figure 1. The first step in this process is smooth-muscle cell excitation by either ligand binding (neurotransmitter with its associated receptor) or membrane depolarization. This leads to an increase in free cytosolic calcium. Free cytosolic calcium ion levels are usually ,0.1 mM. Total intracellular calcium concentrations are much higher, indicating a considerable pool of stored calcium. The increase in cytosolic calcium may come from influx across the cell membrane of extracellular calcium through specific voltage-sensitive channels or via release of intracellular stores. The release of intracellular stores can be triggered by second messengers such as inositol trisphosphate (IP3), cyclic AMP, or guanosine triphosphate (GTP). The excess of free cytosolic calcium binds with calmodulin, altering this molecule and allowing it to bind to the enzyme myosin light-chain kinase. Myosin light-chain kinase causes phosphorylation of the myosin light chain, which then interacts with actin, causing a conformational change of these proteins and allowing them to slide over each other, thus shortening the muscle. Adenosine triphosphate (ATP) is a necessary cofactor for this step. This process can be repeated over and over as long as there is a stimulus for contraction. The process of muscle relaxation also depends highly on ATP. A significant amount of energy is expended by certain ATP-dependent pumps (ATPases) as they act to pump calcium (often against tremendous gradients) out of the cell or into storage sites thus allowing calcium homeostasis and cell repolarization.

Figure 1

Neurophysiology of Micturition




The ability of the bladder to accommodate increasing volumes of urine at low pressures is termed bladder compliance. In mathematical terms, it is measured as a change in unit volume per change in pressure (C ¼ DV/DP). A bladder that can hold large volumes of urine at low pressures is “highly” compliant. At physiologic rates of filling (,10 mL/min), bladder pressure rarely rises above 10 cm H2O up to a capacity of 400 –500 cc. This phenomenon is unique to the bladder as an organ if one considers that bladder smooth muscle must undergo a 100 –200% displacement in slack length to create this kind of compliance. The vena cava, in contrast, need only undergo 25 – 50% displacement to produce significant changes in vessel diameter (1). Compliance is a product of both the neuromechanical and viscoelastic properties of the bladder wall. The fact that even acutely denervated bladders maintain adequate compliance underscores the importance of the passive viscoelastic properties in maintaining adequate bladder compliance. The human bladder wall is composed of detrusor smooth muscle interspersed with islands of connective tissue or extracellular matrix (ECM). The ECM is composed of proteins such as collagen, proteoglycans, elastin, and many other molecules that are now being identified. Because bladder muscle does not have a “skeleton” on which to exert force, these ECM proteins are extremely important with regard to energy transmission. They are also crucial to compliance, and any alteration in the composition of the ECM can result in decreased compliance. Such alterations can occur with chronic inflammation, injury, obstruction, or chronic denervation and typically result in increased collagen content and fibrosis. There is no agreement yet on the definition of abnormal compliance values. Ghoniem suggested that a value of ,10 mL/cm H2O is severely impaired compliance and dangerous to the upper urinary tracts, 10– 20 mL/cm H2O is moderately impaired and .20 mL/cm H2O is normal.



The pelvic and hypogastric nerves supply the bladder and urethra with efferent parasympathetic and sympathetic neurons, and both convey afferent (sensory) neurons from these organs to the spinal cord. The storage phase of micturition is controlled primarily by sympathetic, and voiding phase by parasympathetic, vesicourethral innervation. The somatic innervation is important mainly in regard to the musculature of the pelvic floor and the external or striated urethral sphincter (EUS), and is supplied via efferents in the pudendal nerve (2 – 4).


Parasympathetic Supply

The parasympathetic efferent supply is classically described as originating in the intermediolateral region of the gray matter of the spinal cord segments S 2 – 4 and emerges as preganglionic fibers in the ventral roots and exits as the pelvic nerve. This nerve courses deep in the pelvis on each side of the rectum as three or four trunks in human. Bilaterally, at a variable distance from the bladder and urethra, the pelvic and hypogastric nerves meet and branch to form the pelvic plexus, sometimes known as the inferior hypogastric plexus, or plexus of Frankenhauser. This is a plexus of freely interconnected nerves in the pelvic fascia that is lateral to the rectum, internal genitalia, and lower urinary organs. Divergent branches of this plexus innervate these pelvic organs. The hypogastric and pelvic nerves also carry afferent autonomic nerve impulses to synapses in the dorsal column of the lumbosacral spinal cord (2,3).



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Sympathetic Supply

The sympathetic innervation to the lower urinary tract originates in the intermediolateral nuclei of the thoracolumbar spinal cord in segments from T11 through L2 or L3. They traverse the lumbar sympathetic ganglion and join the presacral nerve (superior hypogastric plexus). The hypogastric plexus lies anterolateral to the great vessels at the level of third lumbar to first sacral vertebrae and gives rise to the left and right hypogastric nerves which are really elongated nerve plexuses. These nerve plexuses join the pelvic nerves to form the plexuses of Frankenhauser, from which they spread out to innervate the pelvic organs (5). As demonstrated by Gilepsie, two nerve bundles extended from the inferior hypogastric plexus (plexus of Frankenhauser), each accompanied by artery derived from the vagin*l artery (6). The first bundle (vesicoureteric plexus) parallels the inferior border of the ureter until it reaches the cardinal ligament, from where, some fibers supply the dorsum of the bladder, while the remaining nerve fibers continue to parallel the ureter to pierce the bladder at the level of the interureteric ridge of the trigone. The destruction of this plexus (vesicoureteric plexus) was found effective in the treatment of women with hypersensitive bladder disorders. The second nerve bundle passes downward to the junction of the urethra with the anterior wall of the vagin*. However, more anatomical dissections are needed for this area. Classically, the autonomic nervous system has been regarded as a two-neuron system composed of two neuron models; preganglionic and postganglionic neurons. Elbadawi has nicely reviewed the anatomic aspects of the contemporary modifications of classical autonomic nervous system (7 –11). He stated that the muscular innervation of the lower urinary tract is derived exclusively from postganglionic neurons of what is called the urogenital short neuron system. Although paraganglia and preganglia exist, actual innervation predominantly emanates from peripheral ganglia that are at a short distance from, adjacent to, or within the organs they innervate, thus the name short. The ganglia are composed of three cell types: cholinergic principal neurons, adrenergic principal neurons, and small intensely fluorescent (SIF) cells. The SIF cells are thought to play an important role in modulation of interganglionic vasomotor function and ganglionic transmission. In addition, there are complex intraganglionic networks of cholinergic and adrenergic fibers. Thus, there is a wide variety of modulating synaptic relays. In addition, postganglionic neurons do not necessarily terminate in the peripheral end organ, but many actually terminate within the ganglia of some systems. Increasing scientific work is revealing that the neural control of the lower urinary tract is more complex than had previously been thought.


Somatic Supply

The somatic supply arises from motorneurons in the anterior horn of S2, S3, and S4, clustered in an area known as Onuf’s nucleus. There are contradictory views of the neural supply of the striated sphincter. The EUS is composed of an extramural and intramural component that differ physiologically and will be discussed later. However, most authors agree that the striated sphincter, including both components, is innervated only through motor end plates, implying purely somatic innervation, through there may be differences in opinions regarding the actual nerve trunks carrying these fibers (4,12). In a recent neuroanatomical study, Hollabaugh et al. described an intrapelvic branch of the pudendal nerve that joins the pelvic nerve branch at the level of the proximal urethral sphincter (13). The morphologic evidence of autonomic innervation of the striated sphincter has not been definitively demonstrated in other species or in human. However, Elbadawi and Atta (11) reported that there is evidence for triple innervation (somatic plus cholinergic and adrenergic autonomic) of the intramural striated sphincter of the

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male cat. This finding is supported by electrophysiologic studies (14). These conclusions are applicable only to the intramural portion of the striated sphincter, and other authors’ conclusions regarding the intramural component may have been erroneously drawn from specimens from the adjacent extramural component.





In both the parasympathetic and sympathetic systems, the preganglionic neurotransmitter is acetylcholine, which affects nicotinic cholinergic receptors. The primary postganglionic parasympathetic neurotransmitter is also acetylcholine, which affects muscarinic cholinergic receptors, while the postganglionic sympathetic neurotransmitter is a catecholamine, norepinephrine, which affects the adrenergic receptors. Newer scientific data are supporting the existence of many other neurotransmitters and receptors responsible for lower urinary tract function. These include ATP, nitric oxide (NO), dopamine, serotonin, glutamine, gamma amino butyric acid (GABA), various neuropeptides, and prostanoids. Representative parasympathetic and sympathetic nerve terminals are depicted in Figures 2 and 3.

Figure 2


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Figure 3


Cholinergic Mechanisms

The voiding phase of the micturition cycle is primarily controlled by the parasympathetic nervous system. Stimulation of the pelvic nerves produces a strong, sustained bladder contraction that leads to bladder emptying. Cholinergic receptors are ubiquitous throughout the bladder body but scarce at the region of the bladder neck and the ventral part of the urethra. They are absent in an area called the superficial trigonal muscle. The human bladder has two muscarinic cholinergic receptor subtypes, M2 and M3. M2 receptors predominate immunohistochemically (80% overall), but functional studies show that bladder contractions are mediated primarily by M3 receptors through hydrolysis of phosphoinositol and the resultant release of intracellular calcium (15,16). M1, M2, and M4 receptors are also present prejunctionally on nerve terminals in the bladder and are thought to play a modulating role through amplification (M1) and inhibition (M2 and M4) of acetylcholine release (17,18). Drugs with anticholinergic properties such as propantheline, dicyclomine, imipramine, and oxybutynin have been used for many years to suppress overactive detrusor contractions. The usefulness of these medicines, however, has been somewhat limited owing to their lack of specificity with regard to mucscarinic receptors. Muscarinic receptors are also present extensively in salivary glands, bowel, and the accommodation apparatus of the eye, with M3 receptors predominating in the salivary glands. As a result, the use of standard antimuscarinic drugs often leads to intolerable side effects such as dry mouth, constipation and visual disturbances. Newer, more selective muscarinic antagonists are being developed. Tolterodine, a competitive antagonist that binds all receptor subtypes, was shown in clinical studies to be equal in efficacy to oxybutynin in reducing micturition frequency and urge incontinence episodes while having a lower incidence of dry mouth (19). The apparent bladder selectivity of these newer agents may be due to several factors. The action of these drugs on prejunctional muscarinic receptors may play a larger role than initially thought. In addition, heterogeneity of the M3 receptor population has been postulated. In fact, radioligand-binding studies showed tolterodine and oxybutynin to have similar affinities for M3 receptors in the bladder, but oxybutynin had an eightfold higher affinity for parotid gland M3 receptors. These types of

Neurophysiology of Micturition


sensitivity differences have also been detected with other M3-selective antagonists, darifenacin and zamifenacin (15,20). Botulinum toxin, now commonly used for treatment of skeletal muscle spasticity, inhibits acetylcholine release from cholinergic nerve terminals. It has been used successfully in the treatment of detrusor-sphincter dyssynergia in spinal cord-injured men by injecting it into the external sphincter to lower outlet resistance (21). It is also showing promise as a treatment for bladder hyperreflexia and possibly overactive bladder. Injection of the toxin into detrusor muscle has been effective in suppressing contractions in these patient populations, and further studies are eagerly awaited (22). Bethanechol chloride, a cholinergic agonist, has been used rather commonly to enhance voiding, and this seems theoretically sound. Although cholinergic agonists may raise baseline bladder pressure, the use of such agents does not appear to be clinically useful in promoting bladder emptying (23 –25). There are several reasons for this. Cholinergic agonists appear to cause a reflex sympathetic urethral constriction, prohibiting coordinated voiding (26). Furthermore, cholinergic activation leads to a feedback mechanism via the aforementioned prejunctional M2 and M4 receptors, inhibiting further acetylcholine release. Finally, bethanechol is poorly absorbed from the gastrointestinal tract, necessitating subcutaneous administration or prohibitively high oral doses to achieve pharmacologic effect. C.

Adrenergic Mechanisms

The adrenergic receptors (a and b) have different distributions in the lower urinary tract. The a receptors are distributed mainly in the urethra and bladder neck. They are further subclassified into a1 (postsynaptic) and a2 (presynaptic) receptors. Stimulation of a1 receptors regulates vasoconstriction and smooth muscle contraction, whereas stimulation of a2 receptors inhibits the release of norepinephrine from nerve terminals through a negative feedback mechanism. Several subtypes of the a1 receptor have been identified. Studies have shown that a1 receptors in the urethras of humans are of the a1a subtype (27,28). In addition, radioligand binding has suggested the majority of a receptors in female animals are a2, whereas a1 receptors predominate in the male (29). Phentolamine and phenoxybenzamine are both nonspecific a-adrenergic antagonists and are not routinely used in the treatment of voiding disorders. Prazosin, doxazosin, and terazosin are relatively selective antagonists of a1 receptor sites and are commonly used in the treatment of outlet obstruction in males secondary to benign prostatic hyperplasia because of their relaxing effect on prostatic smooth muscle. The use of these agents is somewhat limited by cardiovascular side effects owing to the presence of a1 receptors throughout the vascular tree. Tamsulosin, an a1a-selective antagonist, targets urethral smooth muscle with a decreased incidence of cardiovascular side effects such as postural hypotension. Although sometimes used to treat female bladder outlet obstruction, the efficacy of these drugs in this capacity has not been definitively established, chiefly owing to a lack of standardized criteria to define this entity in women. Any lack of efficacy may also be explained by the deficiency of a1 receptors in the female urethra. a-Stimulating drugs such as phenylpropranolamine and ephedrine will increase the tone of urethra and bladder neck by stimulating smooth muscle contraction at these sites. In fact, over-the-counter cold medications and decongestants are a common cause of urinary retention in elderly males. It is also for this reason that these drugs have been used in the pharmacologic treatment of stress incontinence in women (30). There have been conflicting animal studies regarding the role of a receptors in the spinal cord, with data to support both inhibitory and facilitative influences. Some studies have indicated an excitatory role for a1 receptors at both the end-organ level and in the spinal cord. These


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effects include the release of NO, the enhancement of acetylcholine release (a1a), and direct excitatory effects on bladder smooth muscle (a1b/a1d) (31,32). This last postjunctional excitatory effect is hardly present in younger animals but becomes prominent in older animals, supporting the concept of neural plasticity and change of adrenergic receptor expression over time. In addition, the intrathecal administration of doxazosin (a1 antagonist) has been shown to suppress bladder hyperactivity and decrease the amplitude of bladder contractions in rats (33). This effect was more pronounced in the setting of chronic bladder outlet obstruction, again suggesting the plastic nature of neural control of the diseased bladder. There is other evidence to support age-related changes in lower urinary tract adrenergic receptor expression, an intriguing concept that may hold promise for future research. b-Adrenergic receptors in the urinary tract (b2) tend to cluster in the bladder body, as opposed to the bladder base and neck. They appear to modulate smooth-muscle relaxation; b stimulants, e.g., terbutaline, cause bladder relaxation and may contribute to urinary retention when given in high doses for premature labor. Unfortunately, b agonists do not appear to be clinically useful in treating detrusor instability (DI) (34). The role of the sympathetic nervous system in the lower urinary tract is a matter of dispute. However, many authors advocate its major role in the lower urinary tract. The sympathetic nervous system acts primarily to facilitate the filling and/or storage phase of micturition and does so by three mechanisms: (a) increasing accommodation by stimulation of b-adrenergic receptors in the bladder body; (b) increasing outlet resistance by stimulation of the predominantly a-adrenergic receptors in the bladder base and proximal urethra and by causing an increase in activity of striated muscle of the pelvic floor (“guarding reflex”); and (c) inhibiting bladder contractility by means of a blocking effect on parasympathetic ganglionic transmission (35,36). Edvardsen postulated a spinal reflex in the cat—with afferents in the pelvic nerves and efferents in the hypogastric nerves—causing bladder relaxation during filling and therefore an increased volume threshold for micturition (37,38). Consistent with this hypothesis is the fact that in the cat b-adrenergic blockade or surgical sympathectomy has been reported to increase bladder activity, decrease bladder capacity, and produce a shift to the left of the accommodation limb of the cystometric curve (39,40). D.

Nonadrenergic, Noncholinergic Mechanisms

The fact that not all bladder contractile activity can be blocked by atropine even with massive doses (the phenomenon of atropine resistance) has led to the postulation of nonadrenergic, noncholinergic (NANC) neurotransmitter system, which is responsible for part of the neurotransmission in the bladder. Experimental studies on bladder muscles have shown that the bladder contraction is biphasic. Only the contraction of the second phase can be blocked by atropine; not the first phase. ATP and other substances are responsible for the contraction of the first phase (41,42). More recently, numerous substances have been shown to play a role in regulation of the lower urinary tract. These substances acting as neurotransmitters or neuromodulators, include an extensive list, e.g., opioids, vasoactive intestinal polypeptide (VIP), serotonin, dopamine, glutamic acid, GABA, ATP, and prostaglandins (F2, E, E2). Many of these substances exhibit both inhibitory and facilitative influence on the micturition cycle at the spinal cord level and higher. These developments have significant potential implications for the future development of drugs affecting nervous control mechanisms in the urinary tract and elsewhere (43,44). However, the role of NANC mechanisms in the contractile activation of the human bladder is still disputed. In normal human detrusor, atropine was found to cause .95% inhibition of electrically evoked contraction (45). In detrusor strips from patients with a diagnosis of unstable bladder or from patients with benign prostatic hyperplasia, atropine

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resistance was found in up to 65% (46). These apparently conflicting data may be explained by differences in the tissues investigated. Ghoniem found a significant atropine-resistant component to the electrically induced detrusor contraction of meningomyelocele patients undergoing augmentation cystoplasty, which was absent in normal bladders of patients undergoing ureteral reimplantation (47). Most probably, normal human detrusor muscle exhibits little atropine resistance while abnormal detrusor exhibits high atropine resistance, making study of NANC mechanisms more attractive in disease states. There is much research being done in this regard, and these studies are eagerly awaited. E.

Purinergic Mechanisms

Purinergic receptors are classified as P1 and P2 based on their affinity for either adenosine or ATP respectively. ATP-sensitive P2 receptors can be subclassified into P2X and P2Y receptor families based on whether the mechanism is ion channel gated (P2X) or G-protein coupled (P2Y). The P2X family can be further subclassified into seven subtypes (P2X1, P2X2, etc.). Levin suggested that purinergic stimulation initiates a bladder contraction (first phase) whereas cholinergic stimulation leads to sustained bladder emptying (48). Chancellor showed that ATP generated a more forceful smooth muscle contraction than a cholinergic agonist, a finding that was corroborated by Sneddon, who showed that purinergic mediated contraction is more forceful in neonates (49,50). Theobald demonstrated a greater rise in bladder pressure in cats treated with purinergic agonists versus cholinergic agonists (51). These findings have not been consistent, however, as others have shown decreased bladder emptying with purinergic agonists (52). Animal studies have implied the presence of multiple types of purinergic (P2X and P2Y) receptors in the bladder and that the response of detrusor muscle to purinergic stimulation is itself biphasic depending on the receptor stimulated (P2X, fast response; P2Y, slow, sustained response) (53). P2X1 receptors have been shown to be dominant in rat detrusor and vascular smooth muscle (54). O’Reilly and coworkers studied P2X receptors and their role in idiopathic DI in human females. They found that P2X2 receptors were increased and other P2X subtypes were decreased in women with idiopathic DI, again demonstrating the trend toward atropine resistance in abnormal bladders (55). These data hold promise as the search for novel approaches to the treatment of overactive bladder and other bladder disorders continues. It is likely that purinergic mechanisms also play an excitatory role at higher sites, including parasympathetic ganglia and afferent nerve terminals in dorsal root ganglia. P2X3 receptors have been identified in neurons in dorsal root ganglia in addition to subepithelial afferent nerves plexuses in the bladder and ureteral wall (54,56). Intravesical administration of ATP activates bladder afferent fibers and desensitization of these afferents with suramin, a purinergic antagonist, decreased reflex bladder activity (57,58). Afferent activity induced by bladder distention was reduced in P2X3 knockout mice (53). These data argue that purinergic mechanisms play a sensory role in the lower urinary tract as well and could provide potential targets for therapy of disorders such as sensory urgency and interstitial cystitis. F.

Dopaminergic Mechanisms

Central dopaminergic pathways appear to exhibit both inhibitory and excitatory influences on micturition, based on the site and receptor type stimulated. D1 or D1-like receptors mediate inhibition whereas D2 or D2-like receptors mediate excitatory reflexes. Activation of D1 receptors in the substantia nigra causes suppression of reflex bladder activity in cats (59). Bladder hyperreflexia produced in monkeys through destruction of these pathways (inducing Parkinson-like motor symptoms) was also suppressed using a D1-like agonist in one study (60).


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From a clinical standpoint, however, treatment in humans with standard anti-Parkinsonian medications does not appear to correlate well with improvement in bladder symptoms or urodynamic findings (61). These patients often require treatment with anticholinergics to control bladder hyperreflexia, underscoring the complex nature of voiding dysfunction. The diversity of dopaminergic influence on micturition is demonstrated by the fact that stimulation of D2-like receptors in animals in both the pontine micturition center (PMC) and in the spinal cord can induce bladder hyperactivity (62,63). It is likely that central dopaminergic pathways play a significant role in micturition, but the translational value of current basic science knowledge to the clinical arena has yet to be realized.


Serotonergic Mechanisms

It is possible that serotonin (5HT) has an impact on neural control of the lower urinary tract at both the central and peripheral levels, although the degree of this impact is still largely unknown. This uncertainty is a product of the multiple receptors that have been identified coupled with the lack of specific drugs with which to target them. There have been at least seven different 5HT receptors identified (5HT1, 5HT2, etc.). Nonetheless, immunohistochemical studies have identified 5HT-containing neurons in the pelvic ganglia. Similarly, 5HT-containing neurons in the raphe nucleus of the caudal brainstem project to the dorsal horn in addition to the autonomic and sphincter motor nuclei in the lumbosacral cord. In cats, activation of these 5HT neurons in the cord inhibits reflex bladder activity and decreases firing of sacral efferents to the bladder (62,64). Administration of 5HT antagonists in animals blocks these effects and causes a decreased functional bladder capacity indicating that descending serotonergic pathways cause tonic inhibition of the afferent limb of the micturition reflex (65). Of interest is the possible role of serotonergic pathways in enuresis or overactive bladder. Tricyclic antidepressants are often used in the treatment of nocturnal enuresis. The efficacy of these agents may be explained by decreased 5HT reuptake, increasing levels available for suppression of reflex detrusor activity. Is has also been shown that the incidence of overactive bladder and urge incontinence is greater in individuals with depression, a condition associated with low levels of 5HT. Peripherally, 5HT has been shown to induce bladder contractions as well as facilitate acetylcholine release from nerve terminals in the bladder via activation of prejunctional receptors (66,67). Anatomically, the sympathetic autonomic nuclei and sphincter motor nuclei receive serotonergic input, and there is evidence to show that sphincter reflexes are facilitated by activation of 5HT receptors as in the case of duloxetine, a combined 5HT and norepinephrine reuptake inhibitor (68,69).


Glutaminergic Mechanisms

Glutamic acid or glutamate plays an important role as a facilatory transmitter in the central pathways controlling micturition. It is present in visceral afferents in the dorsal horn of the lumbosacral cord, spinal interneurons, and the descending pathway from the PMC to the sacral parasympathetic plexus (70,71). Glutamate appears to facilitate bladder function at all of these levels via either NMDA (N-methyl-D-aspartate) or AMPA (a-amino-3-hydroxy-5-methyl-4isoxazoleproprionic acid) receptors. NDMA antagonists depress reflex bladder activity and sphincter electromyographic activity in anesthetized animals as well as animals with cord transection at the midthoracic level (72). This indicates that the spinal reflex pathways controlling micturition rely on glutaminergic transmitter mechanisms. Studies also indicate that differences in bladder and external sphincter sensitivity to glutaminergic suppression may be

Neurophysiology of Micturition


explained by differing receptor expression at each site. In situ hybridization studies have revealed high messenger RNA for AMPA receptor subunits GluR-A and GluR-B in sacral parasympathetic preganglionic neurons, but not NR2 NMDA receptor subunits. Conversely, high levels of messenger RNA for all four AMPA receptor subunits (GluR-A thru D) as well as the NR1 NMDA subunit are expressed in the motorneurons of the EUS (53).


GABA Inhibitory Mechanisms

GABA is a well-known inhibitory transmitter in the central nervous system. It appears to influence micturition at both spinal and supraspinal sites via both GABA-A and GABA-B receptors. In animal studies, injection of a GABA-A agonist into the PMC suppressed reflex bladder activity and intrathecal administration of either GABA-A or GABA-B antagonists increased bladder capacity and decreased voiding pressure (73).



Afferent nerve fibers have been demonstrated in the pelvic, pudendal, and hypogastric nerves (74). In the cat, the afferents subserving the sensation of distension (and active therefore in evoking micturition) are more prominent in muscularis propria layer and are distributed evenly to all regions of the bladder, but the afferents subserving the sensations of pain and conscious touch are more prominent in the submucosa in the regions of trigone and anterior bladder neck. Both pelvic and hypogastric afferent pathways carry nociceptive afferents, whereas afferent pathways from the striated sphincter and from the urethra transmit sensations of temperature, pain, wall distension (urethra), urine passage, and travel in the pudendal nerve (74). Anatomical and electrophysiological studies have shown that sacral afferent fibers projecting from the bladder to the spinal cord are either myelinated (A-delta with fast conduction up to 30 m/sec) or unmyelinated (C-fibers with slow conduction 0.3 m/sec) (75,76). Figure 4 represents a schematic of sensory pathways. A large body of evidence suggests that substance P (SP) and other tachykinins are likely to be involved in afferent neurotransmission in the lower urinary tract via vanilloid receptor (VR1). Exposure of bladder mucosa to the neurotoxin capsaicin, the pungent ingredient in hot pepper, causes the release of SP and produces smooth muscle contraction that can be blocked by SP antagonists and the neurotoxin tetrodoxin. Systemic use of capsaicin produces either partial or complete denervation of capsaicin-sensitive afferents, depending on the dose, species, and the age of experimental animal (77). In rats, intravesical administration of capsaicin causes neuroanatomic or functional changes that prevent bladder afferents from transmitting nociceptive input (78). In humans, capsaicin-sensitive nerves have been postulated. A concentration-dependent reduction in first sensation and bladder capacity occurs following acute administration of intravesical capsaicin. It causes desensitization of C-fiber sensory afferents inducing reversible suppression of sensory neuron activity. These pharmacological data support the use of capsaicin or other neurotoxins to treat painful bladder disorders (79). Resiniferatoxin (RTX), a substance isolated from the cactus plant Euphorbia resinifera, is 1000 times more potent than capsaicin. In contrast, however, RTX has weaker initial excitatory effects than capsaicin on bladder afferents thus eliciting less discomfort. This agent holds significant promise as an alternative to capsaicin in the treatment of both painful bladder disorders as well as detrusor hyperreflexia (80,81).


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Figure 4



There are two types of muscle fibers in the striated sphincter or EUS. The first one is the strongly reactive fast-twitch muscle fibers, and the second is the weekly reactive slow-twitch muscle fibers. Speed of contraction seems to correlate with histochemical reaction for ATP. Resistance to fatigue is directly related to the intensity of oxidative enzyme staining in the same fibers. Slow-twitch fibers are high in oxidative enzyme activity and relatively fatigue resistant. Fasttwitch fibers may be fatigable or relatively fatigue resistant (82). The entire intramural (intrinsic) striated sphincter is composed of slow-twitch fibers, whereas the extramural (extrinsic) component consists of both slow-twitch and fast-twitch fibers. Telealogically, this would be convenient because the intramural striated component would then consist of specialized fibers functionally capable of maintaining tension over prolonged time periods without fatigue. The structure of the extramural component might be related to a role played by this muscle in activity supporting the pelvic viscera and that the slowtwitch fibers are responsible for (background activity) during electromyographic recording. The fast-twitch population of the extramural component is functionally associated with rapid, forceful muscle contraction. It is these fibers then that are recruited to increase the force and speed of contraction of the levator ani during those events that might otherwise cause stress

Neurophysiology of Micturition


incontinence by raising intra-abdominal pressure (83). However, Bazeed and colleagues, studying the dog, reported a different fiber distribution in the intramural component of the striated sphincter (84). They found that the slow-twitch fatigue resistant fibers are only 35%, fast-twitch fatigue-resistant 20%, and fast-twitch fatigable fibers 45% of the intramural striated sphincter. The fast-twitch fibers (fatigable) can convert to slow-twitch fibers by physiotherapy (e.g., electrical stimulation). This is also a theoretical advantage of pelvic floor exercises and behavioral modifications. Some authors explain the success of these therapies for the treatment of urinary incontinence on the basis of changes in the oxidative characteristics of striated muscle. However, other authors have shown that these types of therapies more successfully treat urge incontinence rather than stress incontinence, raising doubt as to the validity of alterations in muscle morphology (85).



It has yet to be resolved whether voiding is the result of a segmental reflex arc that is facilitated and inhibited by supraspinal neurologic pathways, or a long routed reflex that is integrated at higher nervous system levels (86,87). However, in the cat, it appears that the most fundamental micturition reflex is a spinal reflex occurring largely in the sacral micturition center (SMC) at S 2– 4 (88). The spinal cord itself has complex patterns of facilitation and inhibition that take place among the ascending and descending pathways at the spinal cord level. Above the level of the cord, the PMC is located. It is the most important facilitative motor center for micturition, and it is believed that this center serves as the final common pathway for all bladder motor neurons. The region is known as Barrigton’s center and is present in the anterior pons. The cerebellum serves as a major center for coordinating pelvic floor relaxation and force of detrusor contraction. There are extensive cerebellar interconnections with the brainstem reflex centers (87,89). Above this level, the basal ganglia exert inhibitory function on detrusor contractility. Consequently, detrusor hyperactivity is frequently seen in Parkinson’s disease. The cerebral cortex, particularly the frontal lobes and genu of the corpus callosum, exerts primarily inhibitory influences on the micturition reflex. Thus, facilitative influences that release inhibition occur in the upper cortex and permit the anterior PMC to send efferent impulses through the spinal cord allowing a sacral micturition reflex to occur with resultant bladder emptying. Any lesion in these centers can produce a disturbance in bladder function characterized by a reflex coordinated contraction with complete emptying (87,89). A simplified overview of micturition reflexes is shown in Figures 5 and 6. A.

Bradley’s Loop Concept

Bradley et al. described a concept of neurological control of the lower urinary tract in the cat (90). This concept described four loops and circuits that are interconnected by axons, and their integrated output contributes to the determination of the threshold of the detrusor reflex and coordinated synchronized opening of the urethra and relaxation of the urinary bladder. Most of the micturition reflex requires a balanced contribution by all four loops. Loop I: Cerebral-Brainstem Circuit This loop consists of pathways to and from the frontal lobes to the pontine mesencephalic reticular formation, with contribution from the thalamic nuclei in the basal ganglia and


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cerebellum. This loop coordinates volitional control of micturition. It matures during infancy, and may account for voluntary control over the micturition reflex in the childhood. This loop integrity can be demonstrated during cystometry by asking the patient to voluntarily suppress detrusor contraction. Interruption of this circuit severs the micturition reflex from volitional control, e.g., in brain tumor, trauma, cerebrovascular disease (91). Loop II: The Brainstem Sacral Loop This loop consists of pathways from the brainstem (pontine-mesencephalic reticular formation) to the sacral micturition area. Additionally, sensory afferents from the bladder musculature travel directly in the spinothalamic tract to the brainstem without synapsing in the sacral micturition area. These sensory afferent fibers are responsible for the normal sensation of desire to micturate. Loop II is responsible for the occurrence of a coordinated detrusor reflex of adequate duration to produce total evacuation of the intravesical content. Partial interruption of loop II, as in spinal cord injury, results in detrusor reflex of low threshold and the presence of postvoiding residual urine. While abrupt and complete interruption (in spinal shock) produce areflexia and urinary retention. With recovery, uninhibited detrusor reflex contractions appear in the cystogram (92,93).

Figure 5

Neurophysiology of Micturition


Figure 6

Loop III: Vesical-Sacral Sphincter Loop This loop consists of the detrusor nuclei and pudendal nuclei in the gray matter of the sacral spinal cord with their neurons. Sensory afferents in the detrusor muscle travel the detrusor nucleus and influence the closely located pudendal motor nucleus. Pudendal motor neurons terminate in the striated muscular component of the urethral sphincter. Loop III provides the circuit for coordination of detrusor and urethral muscular activity during voiding. Dysfunction of this loop will be manifested in electromyographic recording as either detrusor sphincter dyssynergia or uninhibited sphincter relaxation (94).

Loop IV: Cerebral-Sacral Loop This loop consists of two components: (a) supraspinal and (b) segmental innervation of the peripheral striated muscle. The supraspinal component consists of sensory pathways originating from muscle spindles and tendon organs in the pelvic floor musculature. These axons course through the posterior column and synapse in the thalamus, to reach the pudendal area of the sensorimotor cortex. From there, the motor fibers originate and travel to terminate by synapsing on motor neurons on the pudendal nucleus in the spinal cord. The segmental portion of the loop consists of sensory axons arising from the muscle spindles and tendon organs, which end by


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synapsing on pudendal motor neurons. The pudendal neurons give origin to efferent axons to innervate the pelvic floor musculature and to regulate the sensitivity of spindle stretch receptors. Electromyographic evidence of voluntary contraction of the external sphincter demonstrate an intact loop IV (90,95). B.

Integral Theory of Voiding Reflexes

Mahoney et al. described another concept of micturition as a reflex event that occurs largely in the peripheral autonomic nervous system, permitted to do so by the central nervous system (96). They proposed 12 reflexes operating among bladder, urethra, brainstem micturition center, and spinal cord micturition center. These reflexes could be grouped into four groups according to their function. 1.

Storage-Favoring Reflexes (Four Reflexes)

a. Sympathetic-Detrusor Inhibition Reflex (SDIR). The afferent is the pelvic nerve; the efferent is the hypogastric nerve. This reflex is activated by bladder wall stretch during filling and its function is to inhibit detrusor contraction. b. Sympathetic Sphincter Constrictor Reflex (SSCR). This reflex consists of the same stimulus and pathway as SDIR, but the target organ is the smooth muscle component of the urethral sphincter. It produces an increase in the tone of the sphincter during bladder filling. Together, these two reflexes comprise the “sympathetic stabilizing reflexes” favoring continence of urine (97). c. Perineodetrusor Inhibitory Reflex (PDIR). Stimulation of the stretch receptors of the perineum and pelvic floor muscles produces impulses that travel through pudendal nerve afferents to the SMC. Efferent impulses travel via the pelvic nerve, and the function is inhibition of the detrusor contraction. d. Urethrosphincteric Guarding Reflex (USGR). The stimulus is an increase in mural tension in the trigone and bladder neck during filling or escape of urine into proximal urethra. The afferent limb is via the pelvic nerve to the SMC, and the efferent is via the pudendal nerve to the striated component of the external urethral sphincter producing contraction. 2.

Initiation of Micturition Reflexes (Two Reflexes)

a. Perineobulbar Detrusor Facilitative Reflex (PBDFR). The stimulus is the voluntary contraction of the diaphragm and abdominal wall muscles with simultaneous relaxation of the pelvic floor muscles. The impulse travels through the pudendal nerve and other somatic nerves cranially to the brainstem and brain cortex, which in turn produce stimulation of the SMC. b. Detrusodetrusor Facilitative Reflex (DDFR). An increase in detrusor mural tension produces an impulse that travels via the pelvic nerve to the PMC. The PMC sends facilitative impulses via the lateral reticulospinal tract to the SMC. From here, stimulatory impulses are sent to the detrusor muscle via pelvic nerve efferents producing a detrusor contraction. 3. Intramicturition Reflexes (Five Reflexes) These reflexes are concerned with maintaining a strong detrusor contraction with synchronous relaxation of the sphincter during the voiding phase to provide complete and efficient emptying of the bladder. a. Detrusourethal Inhibitory Reflex (DUIR). The impulse from the detrusor stretch receptors travels via the pelvic nerve to the SMRC producing stimulation, then via the pelvic

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nerve again to the bladder neck and smooth muscle component of the external urethral sphincter producing relaxation. b. Detrusosphincteric Inhibitory Reflex (DSIR). An inhibitory impulse via the pelvic nerves to the “pudendal nucleus” producing relaxation of the striated component of the external urethral sphincter is generated in response to a stimulus from the stretch receptors in the detrusor muscle. c. Urethrodetrusor Facilitative Reflexes (UDFR). Both of these reflexes originate in the proximal urethra and produce detrusor contractions via efferents from the SMC. There are two reflex pathways proposed, one with a brainstem component and one without. Both may act to cause a detrusor contraction in response to the presence of urine in the proximal urethra. d. Urethrosphincteric Inhibitory Reflex (USIR). This reflex has both its afferent and efferent limbs in the pudendal nerves. It is responsible for the prompt synchronous relaxation of the external sphincter at the onset of micturition and is additive to the effect of the DSIR in this regard. 4.

Micturition Cessation Reflex (One Reflex)

a. Perineobulbar Detrusor Inhibitory Reflex (PBDIR). At the end of micturition, inhibitory impulses from the stretch receptors in the perineum and pelvic muscles travel to the brainstem. Efferent inhibitory impulses are then sent to the SMC, thus reestablishing the storage reflexes (Group I).



Much controversy still abounds regarding the exact processes of the micturition cycle, but most experts would agree that it involves two relatively discrete phases: (a) bladder filling and storage, and (b) bladder emptying. From a clinical standpoint, most disorders of voiding can be categorized into a failure of either one of these discrete processes, although quite often there is a combination of the two. While some of the basic concepts of pathways and neural circuits have been around for decades, our understanding of the details of these pathways and circuits has grown tremendously in the past several years. With the advent of functional MRI and PET scanning, as well as the continued discovery of new neurotransmitters and receptors, this knowledge base will continue to develop allowing more effective diagnosis and treatment of voiding dysfunction well into the future.


2. 3. 4. 5.

Zderic SA, Levin RM, Wein AJ. Voiding function and dysfunction. In: Gillenwater JY, Grayhack JT, Howards SS, Duckett JW, eds. Adult and Pediatric Urology. 4th ed. Baltimore: Lippincott Williams & Wilkins, 2002. Keith LM. Anatomy of the pelvis and perineum. In: Clinically Oriented Anatomy. 2nd ed. Baltimore: Williams & Wilkins, 1985:359– 403. Clemente C, ed. Gray’s Anatomy of the Human Body. 30th American ed. Philadelphia: Lea & Febiger, 1985. Romanes GJ. Muscles and fascia. In: Cunningham’s Textbook of Anatomy. Oxford: Oxford University Press, 1972:360– 364. Mitchell BS. Morphology and neurochemistry of the pelvic, and paracervical ganglia. Histol Histopathol 1993; 8(4):761 – 773.

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Ghoniem and Hairston Gilepsie L. Destruction of the vesicoureteric plexus for the treatment of hypersensitive bladder disorders. Br J Urol 1994; 74:40. Elbadawi A. Neuromorphologic basis of vesicouretheral function. I. Histochemistry, ultastructure and function of intrinsic nerves of the bladder and urethra. Neurourol Urodyn 1982; 1:3. Elbadawi A. Autonomic muscular innervation of the vesical outlet and its role in micturition. In: Hinman FJ, ed. Benign Prostatic Hypertrophy. Berlin: Springer-Verlag, 1983:330 –348. Elbadawi A. Ultrastructure of vesicourethral innervation. II. Postganglionic axoaxonal synapses in intrinsic innervation of the vesicourethral lissosphincter. A new structural and functional concept in micturition. J Urol 1984; 131:781. Elbadawi A. Ultrastructure of vesicourethral innervation. III. Anoaxonal synapses between postganglionic cholinergic axons and probably SIF cell derived processes in the feline lissosphincter. J Urol 1985; 133:524. Elbadawi A. Ultrastructure of vesicourethral innervation. IV. Evidence for somatomotor plus autonomic innervation of the male feline rhabdosphincter. Neurourol Urodyn 1985; 4:23. Kakizaki H, Koyanagi T, Kato M. Sympathetic innervation of the male feline urethra rhabdosphincter. Neurosci Lett 1991; 129:165– 167. Hollabaugh RS, Steiner MS, Dmochowski RR. Neuroanatomy of the female continence complex: clinical implications. Urology 2001; 57(2):382– 388. Kakizaki H, Fraser MO, De Groat WC. Reflex pathways controlling urethral striated and smooth muscle function in the male rat. Am J Physiol 1997; 272(5 Pt 2):1647– 1656. Wang P, Luthin GR, Ruggieri MR. Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins. J Pharmacol Exp Ther 1995; 273:959– 956. Hegde SS, Choppin A, Bonhaus D, Briaud S, Loeb M. Functional role of M2 and M3 muscarinic receptors in the urinary bladder of rats in vitro and in vivo. Br J Pharmacol 1997; 120:1409 – 1418. Somogyi GT, De Groat WC. Functional, signal transduction mechanisms, and plasticity of presynaptic muscarinic receptors in the urinary bladder. Life Sci 1998; 64:411– 418. Tobin G, Sjogren C. Prejunctional facilitatory and inhibitory modulation of parasympathetic nerve transmission in the rabbit urinary bladder. J Auton Nerv Syst 1998; 68:153 – 156. Hills CJ, Winter SA, Balfour JA. Tolterodine. Drugs 1998; 55:813 –820. Smith CM, Wallis RM. Characterization of [3H]darifenacin as a novel radioligand for the study of M3 receptors. J Recept Signal Transduct Res 1997; 17:177 – 184. Dykstra DD, Sidi AA, Scott AB, Pagel JM, Goldish GD. Effects of botulinum A toxin on detrusorsphincter dyssnergia in spinal cord patients. J Urol 1988; 139:919– 922. Stohrer M, Schurch B, Kramer G, Schmid D, Daul D, Hauri D. Botulinum A-toxin detrusor injections in the treatment of detrusor hyperreflexia. J Urol 2000; 163:244A. Abstract. D’Agostino G, Kilbinger H, Chiari MC, Grana E. Presynaptic inhibitory muscarinic receptors modulating [3H]acetylcholine release in the rat urinary bladder. J Pharm Exp Ther 1986; 239:522. Mattiasson A, Andersson KE, Elbadawi A. Interaction between adrenergic and cholinergic nerve terminals in the urinary bladder of rabbit, cat and man. J Urol 1987; 137:1017. Alberts P. Classification of the presynaptic muscarinic receptor subtype that regulates 3 H-acetylcholine secretion in the guinia pig urinary bladder in vitro. J Pharmacol Exp Ther 1995; 274:458– 468. Sogbein SK, Downie JW, Awad SA. Urethral response during bladder contraction induced by subcutaneous bethanechol chloride: elicitation of sympathetic reflex constriction. J Urol 1984; 131:791. Testa R, Guarneri L, Ibba M. Characterization of the alpha-1 adrenoceptor subtypes in the prostate and prostatic urethra of rat, rabbit, dog and man. Eur J Pharmacol 1993; 249:307 –315. Chess-Williams R, Aston N, Couldwell C. Alpha-1A subtype mediates contraction of the rat urethra. J Auton Pharmacol 1994; 14:375 – 381. Andersson KE. Pharmacology of lower urinary tract smooth muscle and penile erectile tissues. Pharmacol Rev 1993; 45:253– 307.

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Ghoniem and Hairston Lee HY, Bardini M, Burnstock G. Distribution of P2X receptors in the urinary bladder and the ureter of the rat. J Urol 2000; 163:2002– 2007. O’Reilly MA, Kosaka AH, Knight GF, Chang TK, Ford A, Rymer JM, Popert R, Burnstock G, McMahon SB. P2X receptors and their role in female idiopathic detrusor instability. J Urol 2002; 167:157– 164. Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev 1998; 50:413– 492. Namasivayam S, Eardley I, Morrison JFB. Purinergic sensory neurotransmission in the urinary bladder: an in vivo study in the rat. Br J Urol Int 1999; 84:854 – 860. Dmitrieva N, Burnstock G, McMahon SB. ATP and 2-methyl thio ATP activate bladder reflexes and induce discharge of bladder sensory neurons. Soc Neurosci Abstr 1998; 24:2088. Yoshimura N, Sasa M, Yoshida O, Takaori S. Dopamine D1 receptor-mediated inhibition of micturition reflex by central dopamine from the substantia nigra. Neurourol Urodyn 1992; 11:535–545. Yoshimura N. Mizuta E, Kuno S, Sasa M, Yoshida O. The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with Parkinsonism induced by 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP). Neuropharmacology 1993; 32:315 – 321. Araki I, Kitahara M, Oida T, Kuno S. Voiding dysfunction and Parkinson’s disease: urodynamic abnormalities and urinary symptoms. J Urol 2000; 164:1640 – 1643. De Groat WC, Booth AM, Yoshimura N. Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA, ed. The Autonomic Nervous System. Vol 3. Nervous Control of the Urogenital System. London: Harwood, 1993:227 – 290. Kuno S, De Groat WC, Yoshimura N. Dopaminergic mechanisms underlying bladder hyperactivity in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway. Soc Neurosci Abstr 1999; 25:1686. McMahon SB, Spillane K. Brain stem influences on the parasympathetic supply to the urinary bladder of the cat. Brain Res 1982; 234:237– 249. Steers WD, De Groat WC. Effects of m-chlorophenylpiperazine on penile and bladder function in rats. Am J Physiol Regul Integr Comp Physiol 1989; 257:R1441– R1449. Andersson KE. Changes in bladder tone during filling: pharmacological aspects. Scand J Urol Nephrol Suppl 1999; 201:67– 72. Candura SM, Messori E, Franceschetti GP, D’Agostino G, Vicini D. Neural 5HT4 receptors in the human isolated detrusor muscle: effects of indole, benzimidazolone and substituted benzamide agonists and antagonists. Br J Pharmacol 1996; 118:1965 –1970. Espey MJ, Du HJ, Downie JW. Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats. Brain Res 1998; 798:101 – 108. Danuser H, Thor KB. Spinal 5HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat. Br J Pharmacol 1996; 118:150 – 154. Araki I, De Groat WC. Unitary excitatory synaptic currents in preganglionic neurons mediated by two distinct groups of interneurons in neonatal rat sacral parasympathetic nucleus. J Neurophysiol 1996; 76:215– 226. Matsumoto G, Hisamitsu T, De Groat WC. Non-NMDA glutaminergic excitatory transmission in the descending limb of the spinobulbospinal micturition reflex pathway in the rat. Brain Res 1995; 693:246– 250. Yoshiyama M, Roppolo JR, De Groat WC. Effects of LY215490, a competitive a-amino-3-hydoxy-5methylisooxazole-4-propionic acid (AMPA) receptor antagonist, on the micturition reflex in the rat. J Pharmacol Exp Ther 1997; 280:894 – 904. Kontani H, Kawabata Y, Koshiura R. In vivo effects of g-aminobutyric acid on the urinary bladder contraction accompanying micturition. Jpn J Pharmacol 1987; 45:45 –53. McMahon SB. Sensory-motor integration in urinary bladder function. In: Cervero F, Morrison JFB, eds. Visceral Sensation. Amsterdam: Elsevier Science, 1986:245 – 283. Hulsebosch CE, Coggeshall RE. An analysis of the axon populations in the nerves to the pelvic viscera in the rat. J Comp Neurol 1982; 211:1. Yoshimura N, De Groat WC. Patch clamp analysis of afferent and efferent neurons that innervated the urinary bladder of the rat. Soc Neurosci Abstr 1992; 18(59.7):127. Abstract.

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Maggi CA, Meli A. The sensory-efferent function of capsaicin-sensitive sensory neurons. Gen Pharmacol 1988; 19:1. Chen C, Ma C, De Groat WC. Effects of capsaicin on micturition and associated reflexes in rats. Am J Physiol 1993; 265: R132– R138. fa*gerli J, Fraser MO, De Groat WC, Chancellor MB, Flood HD, Smith D, Jordan ML. Intravesical capsaicin for the treatment of interstitial cystitis: a pilot study. Can J Urol 1999; 6(2):737 – 744. Avenilo A, Cruz F, Coimbra A. Intravesical resiniferatoxin desensitizes rat bladder sensory fibres without causing intense noxious excitation: a c-fos study. Eur J Pharmacol 1999; 378:17– 22. Park WH, Kim HG, Park BJ, Kim DY, Oh DJ, Lim YS. Comparison of the effects of intravesical capsaicin and resiniferatoxin for treatment of detrusor hyperreflexia in patients with spinal cord injury. Neurourol Urodyn 1999; 18:402. Abstract. Gosling JA, Dixon JS. The structure and innervation of smooth muscle in the wall of the bladder neck and proximal urethra. Br J Urol 1975; 47:549 –554. Gosling JA, Dixon JS, Critchley OD, Thompson SA. A comparative study of the human external sphincter and periurethral levator ani muscles. Br J Urol 1981; 53:35–41. Bazeed MA, Thuroff JW, Schmidt R, Tanagho EA. Histochemical study of the urethral striated musculature in the dog. J Urol 1982; 128:406. Stein M, Discippio W, David M, Taub H. Biofeedback for the treatment of stress and urge incontinence. J Urol 1995; 153:641– 643. De Groat WC, Steers WD. Autonomic regulation of the urinary bladder and sexual organs. In: Lowey AD, Spyer KM, eds. Central Regulation of the Autonomic Functions. 1st ed. Oxford: Oxford University Press, 1990:313. De Groat WC. Nervous control of the urinary bladder in the cat. Brain Res 1975; 87:201. Bradley WE, Scott FB. Physiology of the urinary bladder. In: Harrison JH, Gittes RF, Pearlmutter AD. eds. Campbell’s Urology, 4th ed. Philadelphia: W.B. Saunders, 1978:87 – 124. Bradley WE, Rockswold GL, Timm GW, Scott FB. Neurology of micturition. J Urol 1976; 115:481– 486. Fowler CJ. Neurological disorders of micturition and their treatment. Brain 1999; 122(Pt 7):1213– 1231. Andrew J, Nathan PW. The cerebral control of micturition. Proc R Soc Med 1965; 58:553 – 555. Bradley WE, Timm JW, Scott FB. Cystometry. V. Bladder sensation. Urology 1975; 6:654 – 658. Bradley WE, Timm JW, Scott FB. Innervation of the detrusor muscle and urethra. Urol Clin North Am 1974; 1:3– 27. Bhatia NN. Neurophysiology of micturition. In: Ostergard DR, Bent AE, eds. Urogynecology and Urodynamics. Baltimore: Williams & Wilkins, 1991:31– 54. Mahoney DT, Laberte RO, Blais DJ. Integral storage and voiding reflexes: neurophysiological concept of continence and micturition. Urology 1977; 10:95 – 106.

3 Epidemiology of Female Urinary Incontinence Christopher Saigal David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.

Mark S. Litwin David Geffen School of Medicine at UCLA and UCLA School of Public Health, Los Angeles, California, U.S.A.



Urinary incontinence, defined as the involuntary passage of urine per urethra, can be divided into four clinical entities, as defined by the Agency for Healthcare Research and Quality’s clinical practice guidelines (1). These are stress incontinence, in which a rapid increase in intraabdominal pressure causes urine leakage; urge incontinence, in which precipitous, uninhibited detrussor contractions result an urgent need to void and leakage of urine; mixed stress and urge incontinence; and overflow incontinence, in which chronic retention of urine results in passive loss of small amounts of urine as the bladder is filled beyond capacity. Recent estimates of the societal costs attributable to urinary incontinence are as high as $26.3 billion (1995 dollars), in the over-65-year-old population alone (2). Others have estimated the current costs of urinary incontinence to be $16.3 billion (1995 dollars), with 76% of those costs attributable to female incontinence (3). In the latter study, for women, routine care comprised the majority of the cost (70%), although nursing-home admissions (14%) and treatment (9%) were also major contributors. Others have confirmed that urinary incontinence is a significant reason for nursing-home admissions, with incontinent women having twice the risk of admission as continent women (4). Given the burden of this condition on the health and economy of the nation, much work has been done to create a descriptive epidemiology of urinary incontinence.





Increasing age was accepted as one of the risk factors for urinary incontinence at the 1988 National Institutes of Health consensus panel on urinary incontinence (5). Several studies have since documented an increasing prevalence and severity of urinary incontinence with advanced age (6 – 9). This increased prevalence in elderly women may be due to age-related laxity of pelvic musculature and connective tissue supporting the urethra. Additionally, factors in the 45


Saigal and Litwin

elderly such as impaired mobility and/or declining mental status can increase the risk of incontinent episodes. The elderly suffer from significant rates of fecal impaction and constipation, both clinically associated with urinary incontinence (10). B.


Some researchers have questioned whether there is a genetic basis for the connective tissue atrophy and weakness that contribute to stress urinary incontinence. Mushkat and colleagues examined the prevalence of stress urinary incontinence in first-degree relatives of 259 female probands (11). As a control, they collected data on the first-degree relatives of 165 women (matched for age, parity, and weight) without stress urinary incontinence being seen in a gynecology clinic. Prevalence of stress urinary incontinence was almost three times higher (20.3% vs. 7.8%) in first-degree female relatives of women with stress urinary incontinence themselves. These data suggest that there may be familial transmission of traits that can lead to an increased incidence of stress urinary incontinence. C.


Several studies have documented an increased risk for urinary incontinence in women with high body mass indices (BMIs). Estimates of odds ratios for urinary incontinence range from 1.5 (95% confidence interval, 1.15 –1.95) in a study of women using a criteria for high BMI of .26 kg/m2 (12), to 3.0 (95% CI 1.8, 5.0) in a study examining those in the heaviest quartile of BMI (13). Several other studies have suggested a relationship between weight and incontinence (9,14,15). One prospective study of women undergoing a surgical procedure for obesity found a reduction in incontinence after weight loss (16). D.


Data on the risk hysterectomy confers on the development of subsequent urinary incontinence are conflicting. In one large, systematic review of the literature published from 1966 to 1997, Brown and colleagues constructed a summary estimate of the increased odds for development of urinary incontinence in women who undergo hysterectomy (17). They found that among women .60 years of age, those who had a history of hysterectomy had an odds ratio of 1.6 (95% CI 1.4 –1.8) compared to those without such a history. There was not a similar increase in odds for women younger than 60. They concluded that urinary incontinence following hysterectomy might not be seen until many years after the procedure. E.

Pregnancy and Parity

Several studies suggest that parity is a risk factor for urinary incontinence (18 – 20). Investigators have documented incidence rates for urinary incontinence occurring after pregnancy as high as 26% at 6 months, although most women recover continence with time (21). Possible explanations for this relationship lie in pelvic floor denervation due to compression during pregnancy and delivery and stretching or tearing of pelvic floor connective tissue and musculature during pregnancy and delivery. A Danish study which followed a cohort of 278 women for 5 years after delivering their first child found a 5-year prevalence of International Continence Society –defined stress urinary incontinence of 30%, and 5-year incidence of 19%. Use of vacuum extraction or episiotomy during delivery was found to increase the risk of stress urinary incontinence (22). Although in

Epidemiology of Female Urinary Incontinence


another analysis of this group of women, a second delivery did not increase the risk for stress urinary incontinence (23), others have found a linear relationship between number of deliveries and risk of stress urinary incontinence (13). The relative effect of pregnancy itself versus the process of vagin*l delivery on the development of urinary incontinence has been debated. One study addressed this issue with a comprehensive physical exam and medical history on 189 women being seen for menopausal symptoms in a gynecology clinic (24). Ninety-eight of the patients were found to have urinary incontinence, and multivariate analysis revealed that the risk of urinary incontinence was almost five times higher among women with at least one pregnancy than in women who had never been pregnant. The risk was 3.5 times higher among women who had had only cesarean sections than in women who had never been pregnant. These data suggest that pregnancy itself confers risk for urinary incontinence, and calls into question the use of cesarean section to mitigate this risk. However, in a prospective study of 595 nulliparous women undergoing first pregnancy, in whom continence status had been ascertained prior to pregnancy, the relative risk of urinary incontinence when a woman delivered vagin*lly versus via cesarean section was 2.8 (21). F.

Tobacco Use

Some evidence links stress urinary incontinence and urge incontinence with cigarette smoking in women. In a case control study, Bump and McClish examined 606 women with known smoking history (current, former, or never) and recorded the results of urodynamic tests for the 322 women who were incontinent. Urinary incontinence was significantly more prevalent in current and former smokers than in nonsmokers. The odds ratio for urodynamically proven stress urinary incontinence in current female smokers was 2.48 (95% CI 1.60 – 3.84), while the odds ratio for current female smokers with urodynamically proven urge incontinence was 1.89 (95% CI 1.19– 3.02) (25). In further study of the urodynamic characteristics of stress urinary incontinence in smoking and nonsmoking women, Bump and McClish found that smokers were at increased risk despite having stronger urethral sphincters (26). They speculated that increased and more forceful coughing associated with smoking “likely promotes the earlier development of the anatomic and pressure transmission defects that allow genuine stress incontinence and overcomes any protective advantage of a stronger urethral sphincter.” However, other work has not supported a link between smoking and urinary incontinence (15). G.


Some evidence suggests that African-American women have a lower prevalence of urinary incontinence than Caucasian women. In a population-based study of elderly (.70 years old) noninstitutionalized Americans, 16% of African-American women reported an episode of urinary incontinence in the past year, versus 23% of Caucasian women, a statistically significant difference (27). In a population-based survey of 1922 health maintenance organization members, Thom found a significant association between Caucasian race and the reporting of an incontinent episode in the last year (odds ratio 1.8, 95% CI 1.2– 2.8) (13). In addition to racial variation in the prevalence of urinary incontinence in women, race appears to play a role in the distribution of types of incontinence in incontinent women. In a study of 200 consecutive patients with urinary incontinence who were subject to a comprehensive physical exam and urodynamic testing, significant differences were found in the distributions of stress urinary incontinence, urge incontinence, and mixed incontinence between AfricanAmerican and Caucasian patients (28). Stress urinary incontinence was found in 27% of incontinent African-American women, versus 61% of incontinent Caucasian women. Urge


Saigal and Litwin

incontinence was found in 56% of African-American women, versus 28% of Caucasian women. Similar results were obtained in a study by Graham and Mallet, who examined urodynamic findings in 183 African-American and 132 Caucasian women with urinary incontinence (29). African-American women had a significantly lower prevalence of stress urinary incontinence and higher prevalence of urge incontinence than Caucasian women. In stepwise logistic regression, race emerged as a stronger predictor of stress urinary incontinence than age, obesity, tobacco use, parity, and other risk factors. These studies were not population based, as the women studied sought care for their condition. However, if these differences in the distribution of incontinence type reflect the population at large, the higher prevalence of urge incontinence in African-American women may make them a group well served by more intensive urodynamic evaluation of their incontinence. Research examining differences in distribution of the type of incontinence in Hispanic and Caucasian women has not uncovered significant differences with urodynamic evaluation (30).



Estimates of the prevalence of urinary incontinence in non-institutionalized adults vary considerably, from 2% to 55% (31). Variation in published prevalence and incidence rates for this condition may be related to the variety of definitions of incontinence employed in the population-based studies examining the issue. For some studies, urinary incontinence is defined as any involuntary loss of urine per urethra, regardless of frequency, while other studies use definitions with minimum frequency or volume criteria. Another source of variation in the estimates can be attributed to the different populations included in these studies. Urinary incontinence rates are higher in older women and in those confined to nursing homes; studies with a preponderance of either group of women may arrive at higher estimates for prevalence and incidence of the disease. Additionally, variation in response rates to surveys regarding urinary incontinence may produce different estimates of prevalence owing to response bias. A.

Urinary Incontinence in Younger Women

Although urinary incontinence is often perceived as a problem primarily of elderly women, evidence suggests that it has a significant impact on women as young as 18. In a study of 1250 women between the ages of 18 and 44, Turan found the prevalence of urinary incontinence to be 24% (32). In a population-based study of 436 Swedish women between the ages of 20 and 59, investigators followed subjects for 5 years, and administered a gynecologic exam and incontinence questionnaire at the beginning and end of the study. The prevalence of urinary incontinence in the population was 23.6% at baseline and 27.5% at follow-up (33). Similarly, in two large studies of active-duty female Army soldiers, the reported prevalence of urinary incontinence during exercise or work activity was 33% (34,35). Fitzgerald and colleagues sent a urinary incontinence questionnaire to 2000 women who were randomly selected from a population of 4000 employed women (36). The response rate in this study was 57%. Defining urinary incontinence as “the accidental loss of urine at least monthly,” including incontinence both with and without associated increased intra-abdominal pressure or urgency, they found a urinary incontinence prevalence rate of 17.6% in women ,50 years old. In this study, fewer than half of affected women reported urinary incontinence as a problem to their health care provider, underscoring the consistent finding that urinary incontinence is an underreported and undertreated condition.

Epidemiology of Female Urinary Incontinence



Urinary Incontinence in Older Women

In an effort to address the variation in reported estimates of the prevalence of urinary incontinence in older women, Thom et al. performed an extensive literature search and reviewed 90 articles relating to the issue (31). Of these, 21 met inclusion criteria (e.g., they were population based, not limited to institutionalized women, and reported in English). Study sizes ranged from 388 to 18,084 subjects. The median study response rate was 76%. Prevalence data were abstracted and combined, and calculations were made for the prevalence rates in several populations. The mean prevalence of urinary incontinence that occurred “ever” or “ever in the last year” in “older women” (50 years and older) was 34%. The mean prevalence of urinary incontinence occurring on a daily basis in older women was 14%. Thom found that in studies in which it was possible to distinguish between these types of incontinence the proportion of all urinary incontinence attributable to stress incontinence ranged from 30% to 80%. C.


Fewer studies have addressed the issue of incidence of urinary incontinence. The overall incidence rate in the population-based study of 436 Swedish women described above (33) was 2.9% in these younger women, while the incidence of urinary incontinence occurring weekly or more was 0.5%. One study of continent middle-aged women found the incidence of urinary incontinence (occurring monthly) to be 8% at 3 years (37). Nygaard found a 3-year incidence rate of urinary incontinence of 28.6% in a community-based sample of rural elderly women. In his study, a significant number of women had remission of disease, although data were not adjusted for incontinence treatment (8). Another community-based investigation, “The Medical, Epidemiologic, and Social Aspects of Aging” study, found a 1-year incidence rate of 20% in women .60 years of age (38). Urinary incontinence is a common and costly national health problem. Epidemiological data have identified risk factors for urinary incontinence, such as obesity and smoking, which might serve as targets for preventive health interventions. Other data from studies on race and its relationship to specific types of urinary incontinence may help physicians tailor diagnosis and treatment efforts. Data regarding the prevalence of the condition in both younger and older women serve to remind health care providers to be diligent in querying these patients regarding symptoms. Given the many successful therapeutic options open to women with urinary incontinence, an overlooked diagnosis represents a missed opportunity to improve health.

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Agency for Healthcare Research and Quality. Overview: Urinary Incontinence in Adults, Clinical Practice Guideline Update. 1996. http://www.ahrq.gov/clinic/uiovervw.htm Wagner TH, Hu TW. Economic costs of urinary incontinence in 1995. Urology 1998; 51(3):355– 361. Wilson L, Brown JS, Shin GP, Luc KO, Subak LL. Annual direct cost of urinary incontinence. Obstet Gynecol 2001; 98(3):398– 406. Thom DH, Haan MN, Van den Eeden SK. Medically recognized urinary incontinence and risks of hospitalization, nursing home admission and mortality. Age Ageing 1997; 26(5):367– 374. National Institutes of Health. NIH Consensus Statement Online: Urinary Incontinence in Adults; 1988 Oct 3 – 5. http://odp.od.nih.gov/consensus/cons/071/071_statement.htm (date accessed September 2001). Milsom IEP, Molander U. The influence of age, parity, oral contraception, hysterectomy and the menopause on the prevalence of urinary incontinence in women. J Urol 1993; 148:1459 –1462.

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Saigal and Litwin JC B. Urinary incontinence in the community-analysis of a MORI poll. BMJ 1993; 306:832 –834. Nygaard IE, Lemke JH. Urinary incontinence in rural older women: prevalence, incidence and remission. J Am Geriatr Soc 1996; 44(9):1049– 1054. Schmidbauer J, Temml C, Schatzl G, Haidinger G, Madersbacher S. Risk factors for urinary incontinence in both sexes. Analysis of a health screening project. Eur Urol 2001; 39(5):565– 570. Cheater FM, Castleden CM. Epidemiology and classification of urinary incontinence. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14(2):183– 205. Mushkat Y, Bukovsky I, Langer R. Female urinary stress incontinence—does it have familial prevalence? Am J Obstet Gynecol 1996; 174(2):617– 619. Sherburn M, Guthrie JR, Dudley EC, O’Connell HE, Dennerstein L. Is incontinence associated with menopause? Obstet Gynecol 2001; 98(4):628– 633. Thom DH, Van den Eeden SK, Brown JS. Evaluation of parturition and other reproductive variables as risk factors for urinary incontinence in later life. Obstet Gynecol 1997; 90(6):983– 989. Resnick NM. Geriatric incontinence. Urol Clin North Am 1996; 23(1):55 – 74. Brown JS, Seeley DG, Fong J, Black DM, Ensrud KE, Grady D. Urinary incontinence in older women: who is at risk? Study of Osteoporotic Fractures Research Group. Obstet Gynecol 1996; 87(5 Pt 1):715 –721. Bump RSH, Fantl A, McClish D. Obestiy and lower urinary tract function in women: effect of surgically induced weight loss. Am J Obstet Gynecol 1992; 167:392 –399. Brown JS, Sawaya G, Thom DH, Grady D. Hysterectomy and urinary incontinence: a systematic review. Lancet 2000; 356(9229):535– 539 (Comment In: Lancet. 2000 Dec 9;356(9246):2012-3 UI: 21013012 Comment In: Lancet. 2000 Oct 7;356(9237):1275 UI: 20523126.) Foldspang AMS, Lam GW, Elving L. Parity as a correlated of adult female urinary incontinence prevalence. J Epidemiol Community Health 1992; 46:595. Milson IEP, Molander U, Arvidsson L, Areksoug B. The influence of age, parity, oral contraception, hysterectomy and menopause on the prevalence of urinary incontinence in women. J Urol 1993; 149:1459. Foldspang A, Mommsen S, Djurhuus JC. Prevalent urinary incontinence as a correlate of pregnancy, vagin*l childbirth, and obstetric techniques. Amer J Public Health 1999; 89(2):209– 212. Farrell SA, Allen VM, Baskett TF. Parturition and urinary incontinence in primiparas. Obstet Gynecol 2001; 97(3):350– 356. Viktrup L, Lose G. The risk of stress incontinence 5 years after first delivery. Am J Obstet Gynecol 2001; 185(1):82– 87. Viktrup L, Lose G. Lower urinary tract symptoms 5 years after the first delivery. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11(6):336– 340. Fau´ndes A, Guarisi T, Pinto-Neto AM. The risk of urinary incontinence of parous women who delivered only by cesarean section. Int J Gynaecol Obstet 2001; 72(1):41 –46. Bump RMD. Cigarette smoking and urinary incontinence in women. Am J Obstet Gynecol 1992; 167(5):1213– 1218. Bump R. Cigarette smoking and pure genuine stress incontinence of urine: a comparison of risk factors and determinants between smokers and nonsmokers. Am J Obstet Gynecol 1994; 170(2): 579– 582. Fultz NH, Herzog AR, Raghunathan TE, Wallace RB, Diokno AC. Prevalence and severity of urinary incontinence in older African American and Caucasian women. J Gerontol Ser A Biol Sci Med Sci 1999; 54(6):M299– M303. Bump R. Racial comparisons and contrasts in urinary incontinence and pelvic organ prolapse. Obstet Gynecol 1993; 81(3):421– 425. Graham CA, Mallett VT. Race as a predictor of urinary incontinence and pelvic organ prolapse. Am J Obstet Gynecol 2001; 185(1):116– 120. Mattox TF, Bhatia NN. The prevalence of urinary incontinence or prolapse among white and Hispanic women. Am J Obstet Gynecol 1996; 174(2):646 –648. Thom D. Variation in estimates of urinary incontinence prevalence in the community: effects of differences in definition, population characteristics, and study type. J Am Geriatr Soc 1998; 46(4):473– 480.

Epidemiology of Female Urinary Incontinence 32. 33.

34. 35. 36. 37. 38.


Turan C, Zorlu CG, Ekin M, Hancerlio N, Sarac¸o F. Urinary incontinence in women of reproductive age. Gynecol Obstet Invest 1996; 41(2):132 –134. Samuelsson EC, Victor FT, Sva¨rdsudd KF. Five-year incidence and remission rates of female urinary incontinence in a Swedish population less than 65 years old. Am J Obstet Gynecol 2000; 183(3):568– 574. Sherman RA, Davis GD, Wong MF. Behavioral treatment of exercise-induced urinary incontinence among female soldiers. Mil Med 1997; 162(10):690– 694. Davis G, Sherman R, Wong MF, McClure G, Perez R, Hibbert M. Urinary incontinence among female soldiers. Mil Med 1999; 164(3):182– 187. Fitzgerald ST, Palmer MH, Berry SJ, Hart K. Urinary incontinence. Impact on working women. Aaohn J 2000; 48(3):112 –118. Burgio K, Matthews K, Engel B. Prevalence, incidence and correlates of UI in healthy, middle-aged women. J Urol 1991; 146:1255 –1259. Herzog AR, Fultz NH. Prevalence and incidence of urinary incontinence in community-dwelling populations. J Am Geriatr Soc 1990; 38(3):273– 281.

4 Quality-of-Life Issues in Incontinence David F. Penson* University of Washington, Seattle, Washington, U.S.A.

Mark S. Litwin David Geffen School of Medicine at UCLA and UCLA School of Public Health, Los Angeles, California, U.S.A.



Urinary incontinence is a common condition in older women (1). However, unlike other common medical conditions, such as coronary artery disease or cancer, one cannot measure the public health impact of urinary incontinence in terms of years of life lost or overall mortality. Nonetheless, there is little doubt that urinary incontinence has a considerable impact on patients’ health, well-being, and overall quality of life. The problem facing clinicians and researchers alike is finding ways to measure outcomes objectively in women with this common condition. Objective measures, such as urodynamic assessments and urinary pad tests, often used when studying urinary incontinence, may provide important clinical information during the diagnostic evaluation of urinary incontinence. However, they are not always meaningful to patients. For example, some women who report urinary leakage at home cannot reproduce their symptoms during urodynamic evaluation (2). Others may experience minimal leakage during pad testing but find even the smallest leak to be a problem (3). Finally, some patients may present with symptoms such as urgency or dysuria, which cannot be easily quantified with objective tests (4). These observations underscore the need to find ways to measure patient experience in urinary incontinence accurately, as the ultimate goal of treatment for this condition is to improve quality of life. Advances in research methodology now allow reliable collection of meaningful data on patients’ health-related quality of life (HRQOL). HRQOL includes both objective evaluation of functional status and patients’ perceptions of their own health and its impact on their existence. In the past decade, several valid and reliable questionnaires have been developed that are specifically designed to measure HRQOL in urinary incontinence. These instruments can be used to quantify the qualitative, subjective outcomes, allowing us to capture the public health impact of urinary incontinence on women and better assess the effectiveness of existing therapies for this common condition. *Current affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A. 53


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The goal of this chapter is to provide background on HRQOL research as it applies to urinary incontinence and to present an overview of the existing instruments available for patients with urinary incontinence. In addition, we will summarize the literature on the impact of urinary incontinence on quality of life. II.


HRQOL encompasses a wide range of human experience, including the daily necessities of life, such as food and shelter, intrapersonal and interpersonal responses to illness, and activities associated with professional fulfillment and personal happiness (5). Most importantly, HRQOL involves patients’ perceptions of their own health and ability to function in life. HRQOL is often confused with functional status (6). While functional status is an important dimension of HRQOL, other aspects of HRQOL, such as role function, vitality, mental health, and psychosocial interactions, are equally important. Health-related quality of life is a patient-centered variable, measured using questionnaires or surveys (also known as instruments), which are administered directly to patients in an objective, nonjudgmental manner. The principles of psychometric test theory are used to design instruments that measure HRQOL in a reproducible, quantifiable manner (7). HRQOL instruments typically contain questions, or items, that are organized into scales. Each scale measures a different aspect, or domain, of HRQOL. Responses to the items in a given scale are tabulated to produce a numerical score within that domain, which can then be used for statistical testing. Numerical values typically range from 0 to 100, the higher numbers representing better outcomes. Many health care providers mistakenly believe that they can accurately estimate a patient’s quality of life during the clinical interaction, obviating the need for patient-centered data collection. In one study of 2252 men with localized prostate cancer, patients’ selfassessment of urinary HRQOL was compared with physicians’ assessment. While 97% of patients reported some impairment due to urinary incontinence, only 21% of physicians reported that their patients were impaired by this problem (P , .0001). Similar findings were noted when assessing impairment due to urinary frequency (97% of patients as opposed to 19% of physicians, P , .0001) or due to decreased stream (97% vs. 14%, P , .0001) (8). This study demonstrates the difficulty providers have when trying to assess their patients’ quality of life and underscores the need to use patient-centered instruments when assessing this outcome. HRQOL instruments may be general or disease specific. General HRQOL domains address the components of overall well-being, while disease-specific domains focus on the impact of particular organ dysfunctions that affect HRQOL (9). General HRQOL instruments typically address general health perceptions, sense of overall well-being, and function in the physical, emotional, and social domains. Disease-specific HRQOL instruments for patients with urinary incontinence focus on more directly relevant domains, such as urinary leakage, urgency, and lifestyle changes due to urinary problems or distress/anxiety caused by urinary dysfunction. When studying quality of life in urinary incontinence, it is important to measure both general and disease-specific domains to obtain a complete portrait of the patient’s experience. III.


The development and validation of a new HRQOL instruments is a long and arduous process that should not be undertaken lightly. Therefore, it is always preferable to use established instruments when available. An added advantage of using existing HRQOL instruments is that it

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allows clinicians to compare their results to other, previously studied populations and assess their own outcomes. When instruments are developed, they are first pilot tested to ensure that the target population can understand and complete them with ease. Pilot testing may reveal problems that might otherwise go unrecognized by researchers. For example, many commonly used medical terms are poorly understood by patients. This may result in missing data if patients leave questions blank. Furthermore, because many patients with urinary incontinence are older and may have poor eyesight, pilot testing often identifies easily corrected visual barriers such as type size and page layout. Pilot testing is a necessary and valuable phase of instrument development. Instruments are also evaluated for the two fundamental psychometric statistical properties of reliability and validity. Reliability refers to how reproducible the scale is—in other words, what proportion of a patient’s test score is true and what proportion is due to individual variation. Test-retest reliability is a measure of response stability over time. It is assessed by administering scales to patients at two separate time points, usually a short period apart. If too long an interval transpires, real change in the variable may artificially deflate test-retest reliability coefficients. The correlation coefficients between the two scores reflect the stability of responses. Internal consistency reliability is a measure of the similarity of an individual’s responses across several items, indicating the hom*ogeneity of a scale (7). The statistic used to quantify the internal consistency, or unidimensionality, of a scale is called Cronbach’s coefficient alpha (10). Generally accepted standards dictate that reliability statistics measured by these two methods should exceed 0.70 (11). Validity refers to how well the scale or instrument measures the attribute it is intended to measure. Validity provides evidence to support drawing inferences about HRQOL from the scale scores. Three types of validity are usually evaluated in scales and instruments. Content validity involves a nonquantitative assessment of the scope and completeness of a proposed scale (12). Although more superficial, it is always included in the early stages of instrument development. Criterion validity is a more quantitative approach to assessing the performance of scales and instruments. It requires the correlation of scales scores with other measurable health outcomes (predictive validity) and with results from other established tests (concurrent validity). For example, the predictive validity of a new HRQOL scale for physical function might be correlated with the number of subsequent physician visits or hospitalizations. Likewise, the concurrent validity of a new urinary function scale might be correlated with daily pad use in a urinary pad test. A new emotional HRQOL scale might be correlated with an established mental health index. Generally accepted standards dictate that validity statistics should exceed 0.70 (11). Construct validity is the most valuable yet most difficult way of assessing a survey instrument. It is often determined only after years of experience with a survey instrument. It is a measure of how meaningful the scale or survey instrument is when in practical use. Often, it is not calculated as a quantifiable statistic. Rather, it is frequently seen as a Gestalt of how well a survey instrument performs in a multitude of settings and populations over a number of years. Construct validity requires much effort over many years of evaluation.




General HRQOL Instruments

Although there are over 50 established and published instruments designed to measure general HRQOL, few have been used in the specific setting of primary urinary incontinence. These


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include only the RAND 36-item Health Survey (SF-36), the Sickness Impact Profile (SIP), and the Nottingham Health Profile. Many researchers feel that the SF-36 is the “gold standard” for measuring general HRQOL in medical research (6). Developed during the Medical Outcomes Study, a large study that examined health-related aspects of daily life in many different types of patients (13), it is a 36-item, self-administered instrument that takes ,10 min to complete and quantifies HRQOL in eight multi-item scales that address different health concepts: physical function, social function, bodily pain, emotional well-being, energy/fatigue, general health perceptions, and role limitation due to physical or emotional problems. Two summary scales, a physical health composite and a mental health composite, may also be calculated (14). Each of the eight individual scales is scored from 0 to 100, with higher scores corresponding to better outcomes. The composite scales are standardized to a population mean of 50 with a population standard deviation of 10. Importantly, the SF-36 has been used in prior studies of patients with urinary incontinence and has been shown to perform well in this patient group (15). There is also a shortened version of the SF-36, known as the SF-12, which can be used in place of the SF-36 if the researcher wishes to reduce the respondent burden. Although the results are not reported in eight distinct domains, as with the SF-36, the two summary domains generated in the SF-12 are still acceptable in many research settings. The SIP is considerably longer (136 items) than the SF-36. However, the greater number of questions results in more domains—12—which may allow for a more comprehensive view of general HRQOL. Individual summary scores can be generated for each of these domains (16,17). The Nottingham Health Profile contains six domains comprising a total 38 items that the subject responds to with binary (yes/no) answers (18). It has been used primarily in the United Kingdom to measure general HRQOL in a number of disease processes (19 – 21). While not as widely used in the general population as the SF-36, both of the Nottingham Health Profile and the SIP have been successfully utilized to measure general HRQOL in women with incontinence (22,23). In a recent review of HRQOL instruments for use in incontinence, Corcos and colleagues (24) concluded that these three generic HRQOL instruments were not responsive to change in incontinent patients. This observation underscores the need for valid, reliable, and responsive disease-specific HRQOL instruments in incontinence. B.

Disease-Specific HRQOL Instruments

There are now numerous HRQOL instruments designed specifically to look at the impact of both stress and urge incontinence on HRQOL. No one instrument has been demonstrated to be superior to another, and the choice of outcome measure should be based upon one’s particular clinical or research goals. Most of these questionnaires are available in the public domain. Interested clinicians and researchers can therefore review the items in an instrument and select the established questionnaire that best suits their purposes. The Incontinence Impact Questionnaire (IIQ) and the Urogenital Distress Inventory (UDI) are two of the most common questionnaires used to measure disease-specific HRQOL in urinary incontinence. Developed in the mid 1990s, the original versions of these questionnaires were relatively long (roughly 53 items combined) (25). The two questionnaires had the advantage of adequately capturing both dysfunction and bother due to urgency, frequency and incontinence, etc. The IIQ generates four domain subscores: physical activity, travel, social, and emotional. The IIQ and UDI were specifically designed for females with urinary incontinence and have been extensively tested in this population and shown to be valid and reliable. The IIQ has been shown to perform well in both English- and French-speaking women (26). In clinical practice, however, the questionnaires were cumbersome to complete, which limited their utility. This was

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remedied with the development of short-form versions of these questionnaires—the IIQ-7 and the UDI-6. Although the information obtained is not as detailed, it is adequate and still provides a relatively comprehensive measure of disease-specific HRQOL in women with urinary incontinence. In addition, the IIQ-7 and UDI-6 have been shown to be responsive to change. In a group of 55 women with pelvic organ prolapse, FitzGerald et al. (27) found that women who reported subjective continence following surgery for this condition also reported lower IIQ-7 and UDI-6 scores (better HRQOL) when compared to baseline. Finally, although not originally developed for men, the IIQ-7 and UDI-6 have since been used in a population of older men and have performed well (28,29). The IIQ and UDI instruments have also been modified for use in various subsets of patients with specific forms of urinary dysfunction. Lubeck et al. (30) developed and validated modified versions of the IIQ and UDI specifically for use in patients with urge incontinence and overactive bladder, known as the Urge-Incontinence Impact Questionnaire (U-IIQ) and the Urge-Urinary Distress Inventory (U-UDI). The U-IIQ and the U-UDI are longer (42 items) than the IIQ-7 and UDI-6, but have the advantage of measuring the impact of urgency, frequency, and urge incontinence on HRQOL in much greater detail. HRQOL is measured in seven domains: severity of urge symptoms, and impact on travel, activities, feelings, physical activities, relationships, and sexual function. The instrument has good psychometric properties and appears to capture most of the psychosocial concerns of patients with overactive bladder. Similarly, Barber and colleagues (31) modified the IIQ and UDI instruments for use in women with pelvic floor disorders. The new instruments, known as the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ), contain six scales. The PFDI consists of 61 items and generates scores in three domains: distress due to urinary incontinence, distress due to colorectal-anal dysfunction; and distress due to pelvic organ prolapse. The PFIQ includes 93 items and measures life impact in the same three domains. While the new scales have been shown to have acceptable criterion validity, further use in the clinical and research setting is needed to determine if the total number of items on the PFIQ and PFDI will affect subject’s willingness to complete the questionnaire. The Bristol Female Lower Urinary Tract Symptoms (BFLUTS) instrument is a modified version of the ICSmale survey questionnaire that was developed to measure lower urinary tract symptoms (LUTS) in males (32). To develop the BFLUTS, the majority of the items on voiding symptoms in the ICSmale questionnaire were replaced with items quantifying the frequency and extent of urinary incontinence. The new questionnaire contains 20 items that address urinary incontinence, voiding symptoms in the voiding and storage phase, sexual function, and other aspects of quality of life. The BFLUTS was shown to be valid and reliable in a population of 85 incontinent women from the United Kingdom. It has the advantage of capturing both function and bother in the urinary domains, which are both important components of HRQOL. Although the BFLUTS has not been formally validated in men, a modified version of the questionnaire has been administered to males and was shown to perform well (33). Kelleher et al. developed a 21-item survey, known as the King’s Health Questionnaire, to assess HRQOL in incontinent women (34). This questionnaire measures the domains of general health perception, incontinence impact, urinary symptoms, severity of disease, role limitations, physical limitations, social limitations, personal limitations, emotional problems, and sleep disturbances. It has been shown to be valid and reliable and correlates well with outcomes from the SF-36. Black and colleagues (35) developed two instruments, a Symptom Severity Index (SSI) and a Symptom Impact Index (SII), to assess the impact of incontinence on women’s HRQOL. They developed their instruments in a population of 442 women undergoing surgery for stress urinary incontinence. The new questionnaires have the advantage of being brief (eight items


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total), yet able to generate to distinct summary scores that show acceptable validity and reliability. Research is ongoing to assess the responsiveness of these instruments to change. Patrick et al. (36) have developed the I-QOL, a 22-item questionnaire, that specifically examines HRQOL in three domains, avoidance and limiting behavior due to incontinence, social embarrassment, and psychosocial impact of incontinence. This instrument has the advantage of being developed and test in both sexes and has been cross-culturally adapted for use in numerous countries in various languages (37). As it does not capture urinary function well, it should be used with a functional scale, such as a voiding diary or the SSI. The York Incontinence Perceptions Scale (YIPS) is a simple eight-item questionnaire that is specifically designed to capture a subject’s psychosocial adjustments to urinary incontinence (38). This instrument, like most of the others described so far, tends to focus on stress incontinence, and is therefore of less utility when studying urge incontinence or overactive bladder. If the YIPS were to be used in this setting, it would need to be accompanied by other instruments that capture the impact of urgency and frequency on HRQOL. The 24-item Urge Impact Scale (URIS) (39) has the added advantage of examining urge incontinence in particular, although it doesn’t specifically capture the impact of urgency or overactive bladder on HRQOL.



Although urinary incontinence is traditionally thought of as a condition that affects quality of life, there are few studies that quantify the impact of this health problem on general healthrelated quality of life. However, the studies that have been performed clearly demonstrate that this condition has a broad effect on quality of life. Using the Nottingham Health Profile, Grimby, et al. (40) measured general HRQOL in 120 elderly women (mean age 75.4 years) with urinary incontinence. As a comparison group, 313 age-matched women without urinary incontinence also completed the questionnaire. They found that incontinent women experienced greater emotional disturbance and social isolation than the age-matched controls. When they compared women with either stress or urge incontinence to the control group, they found that the women with urge incontinence had significantly greater emotional disturbance than the controls, while no differences were noted between women with stress incontinence and controls in this domain. Both groups (stress and urge incontinence) reported more social isolation than the controls. Direct comparisons between women with stress and urge incontinence were hindered by sample size issues. Although these data demonstrate that all types of urinary incontinence have a broad impact on women’s daily lives and cause significant social isolation, they also underscore the fact that the quality-of-life impact of urge incontinence is uniquely different from that of stress incontinence. In another study, Haggland et al. (41) used a population-based approach to assess the impact of stress and urge incontinence on HRQOL (as measured by the SF-36) in Surahammar, Sweden. HRQOL data were available in 596 women without incontinence, 440 women with stress incontinence, and 71 women with urge incontinence. Incontinent women, regardless of type, reported significantly lower general HRQOL scores in all eight domains of the SF-36. However, when stratified by type of incontinence, women with urge incontinence reported significantly worse general HRQOL in all domains even when compared to women with stress incontinence. The magnitude of difference in general HRQOL scores between women with stress, as opposed to urge, incontinence was particularly striking, 10– 20 points lower in all domains, and underscores the clinical importance of these findings. Similarly, Hunskaar and Visnes used the Sickness Impact Profile to specifically compare women with urge incontinence

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to those with stress incontinence and found that the group with urge incontinence had significantly worse HRQOL in the sleep and social interaction domains of the SIP. In addition, they divided their cohort by age, comparing HRQOL in 36 incontinent women aged 40– 60 years and 40 women age 70 years, while controlling for type of incontinence. Younger women had worse HRQOL than older women, particularly in the domains of emotional behavior and effect on recreation and pastimes. This study demonstrates that the effect of incontinence on general HRQOL is affected not only by the type of incontinence but also by the age of the patient. Interestingly, it is not simply incontinent episodes that affect quality of life in urge incontinence. In a telephone study of overactive bladder (OAB), Liberman and colleagues administered the SF-36 to 483 subjects with OAB symptoms and 191 controls. After adjusting for age, sex, and use of medical care, subjects with incontinent OAB (n ¼ 185) had worse HRQOL in the physical function, role-functional, bodily pain, health perceptions, social functioning, and mental health domains of the SF-36 when compared to controls. However, in the subgroup of patients with overactive bladder symptoms and no incontinence (n ¼ 298), significantly lower HRQOL scores were still noted in the role-functioning, mental health, health perception, and bodily pain domains. The investigators further divided this population into continent OAB patients with frequency only (n ¼ 175), urgency only (n ¼ 80), and both frequency and urgency symptoms (n ¼ 43). Of these three subgroups, only patients with continent OAB who experience both frequency and urgency have significant lower HRQOL scores than controls. This association was noted in all domains except for social function. This study, and others (42) indicate that, while much of the quality of life impact of urge incontinence is due to the actual leakage episodes, the combination of frequency and urgency symptoms, in and of itself, also affects quality of life. It is also notable that urinary incontinence can have a significant impact on psychological health, which may in turn impact general HRQOL. In a study of 668 adults seen in 41 community primary care practices in North Carolina, 43% of patients who reported urinary incontinence also noted depressive symptoms, as opposed to 30% in patients without urinary incontinence. Furthermore, in the 230 subjects who reported urinary incontinence, lower domain scores in physical and mental health, life satisfaction, and the perception that incontinence interfered with daily life were significant predictors of depression (43). Other studies have found a similar relationship between urinary incontinence and depression and social isolation (44,45). In conclusion, urinary incontinence and lower urinary-tract symptoms appear to impact healthrelated quality of life extensively, affecting physical, psychological, and emotional domains to a greater degree than clinicians might expect.



Given the broad impact of urinary incontinence on health-related quality of life as described above, it is important that we document that treatment for urinary incontinence result in improved quality of life for our patients. Although the field of health-related quality-of-life research in urinary incontinence is still young, several authors have used validated HRQOL instruments to document that successful incontinence treatment results in improved quality of life. A.

Behaviorally Based and Other Noninvasive Interventions

A number of investigators have explored the impact of noninvasive approaches for urinary incontinence on health-related quality of life. These studies have all used validated instruments to demonstrate that quality of life in incontinent women can be improved with the use of


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behaviorally based or other non invasive interventions. For example, Bo and colleagues (46) randomized 59 women with stress incontinence to either pelvic floor muscle exercises or no intervention for a period of 6 months. General HRQOL was assessed using a modified version of an existing Norwegian quality-of-life instrument, while disease-specific HRQOL was assessed using the BFLUTS instrument. Although there were no differences in general HRQOL at the end of the trial, women in the behavioral intervention arm experienced a significant improvement in disease-specific HRQOL. In particular, patients in the pelvic floor exercise group had significantly fewer problems with interference with social life (4% vs. 41% in controls), fewer problems with interference with physical activity (44% vs. 79% in controls), less overall influence of incontinence with life (58% vs. 82% in controls), and less dissatisfaction if the subject had to spend the rest of her life with her current urinary symptoms (4% vs. 38% in controls). While the study could be criticized as having a placebo effect, as there is no way to blind patients to a behavioral intervention, it still demonstrates that women who use pelvic floor muscle exercises for urinary incontinence can expect to have improved disease-specific quality of life. A number of studies have examined the impact of urinary control inserts on quality of life. Sand et al. (47) used the SF-36 to assess HRQOL in 63 women who used the Reliance urinary control insert. Fully 79% of patients reported that they were completed dry with this device. Importantly, patients reported significant improvement in the physical function domain of the SF-36. The SF-36 and the IIQ were used in another study that assessed the impact of a vagin*l device (continence guard) on urinary incontinence and HRQOL. In this study of 55 women with stress incontinence, no differences were noted in the general domains of the SF-36, but significant improvements were seen in disease-specific HRQOL as measured by the IIQ. Other studies have noted similar findings (48). Taken as a whole, it appears that the behaviorally based or noninvasive therapies for urinary incontinence appear to have little impact on general HRQOL, but result in dramatic improvements in disease-specific HRQOL. Further research is needed to confirm or refute these preliminary observations. B.

Medical Management of Urinary Incontinence

Medical therapy has an important role in the treatment of urge incontinence and overactive bladder. Prior to the introduction of disease-specific HRQOL questionnaires in the past 5 years, little information was available regarding the impact of these medications on the quality of life of patients with these conditions. However, the majority of recent randomized clinical trials of new agents for this condition include HRQOL, measured with validated instruments, as an important outcome measure. For example, Dmochowski et al. (49) recently completed a double-blind randomized clinical trial (RCT) of the safety and efficacy of a transdermal oxybutynin patch in subjects with urge and mixed incontinence. There were three groups of patients receiving active agent of varying doses (n ¼ 125 – 133), and one placebo group (n ¼ 132). Outcomes included number of weekly incontinence episodes, adverse events, and changes in HRQOL, as measured by the IIQ. Patients in the highest dosing group (3.9 mg daily) reported improvement in all functional measures, such as number of weekly incontinence episodes and average daily urinary frequency, when compared to placebo but, importantly, also reported a significant improvement in diseasespecific HRQOL, with a reduction in mean IIQ score from 144 at baseline to 89 at the end of the 3-month trial. Similarly, Naglie et al. (50) performed an RCT to assess the efficacy of a calcium channel blocker, nimodipine, in detrusor instability and overactive bladder. Like the prior study, they assessed functional outcomes and HRQOL using the IIQ. Again, significant improvements in

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disease-specific HRQOL were noted in the active treatment arm of the study. Other authors have used the IIQ-7 (51) and the I-QOL instruments (52) to demonstrate the beneficial impact of effective medical therapies for urinary incontinence on quality of life. Given these prior studies, and the wide availability of disease-specific HRQOL instruments for urinary incontinence, it is safe to say that any future randomized clinical trial of new agents for this condition would be considered incomplete without the inclusion of HRQOL as an important endpoint. C.

Surgical Treatment of Urinary Incontinence

Health-related quality of life can and should be assessed following surgical therapy for urinary incontinence. Like other treatment modalities for this condition, there are few published studies to date that have used validated instruments to assess this outcome, but this number should increase in the coming years. To date, there have been studies assessing HRQOL following Burch colposuspension (53), pubovagin*l sling procedures (54), and tension-free vagin*l tape placement (55). Bidmead et al. (53) assessed videourodynamic and HRQOL outcomes in 83 consecutive women who underwent the Burch procedure at a single institution. HRQOL was measured using the King’s Health Questionnaire. Ninety-two percent of women were “objectively cured” according to videourodynamic testing. Accordingly, 95% of women reported improved HRQOL, although only 28% of women reported 50% improvement in HRQOL. This study demonstrates the importance of measuring both “objective” and “subjective” outcomes following surgical treatment for urinary incontinence, as patients who may be “objectively cured” may still experience minor decrements in quality of life that may be amendable to additional, nonsurgical therapy. Morgan et al. (54) used a cross-sectional design to study the long-term efficacy of pubovagin*l sling in 247 women who underwent this procedure in the mid-1990s. In addition to assessing efficacy, the investigators also measured HRQOL outcomes using the UDI-6 instrument. With a mean follow-up of 51 months, the overall objective continence rate was 88%, with 26% of patients who experienced urge incontinence preoperatively having persistent symptoms, and 7% of patients reporting de novo urge incontinence. Summary scores from the UDI-6, usually reported on a scale from 0 to 18 with lower scores being better quality of life, were transformed into a 0 – 100 scale. Ninety-two percent of patients reported transformed scores of ,20 (implying good quality of life), closely mirroring the overall objective continence rate. Surprisingly, patients with de novo urge incontinence also reported reasonable HRQOL (mean score 24) while those with persistent urge incontinence reported significantly worse HRQOL (mean score 44). These results demonstrate that patients’ expectations can play an important role in HRQOL outcomes, as patients with similar objective urge incontinence symptoms had differing HRQOL experiences, depending upon whether these symptoms were present preoperatively.



As urinary incontinence is a highly prevalent condition that has a significant impact on quality of life, it is important that we measure this outcome when studying this incontinence. In the past decade, numerous valid and reliable HRQOL instruments have been developed for use in urinary incontinence. These instruments have been used in various patient populations and are readily available for use in both clinical and research settings. While the exact role of these questionnaires at the bedside is still evolving, it is clear that there is a pressing need for further


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research on the impact of various treatments for urinary incontinence on HRQOL. With information on how these treatments affect quality of life, we can better counsel our patients on which therapy is best for them and what to expect after treatment. This, in turn, will result in better outcomes and better care for incontinent patients.




6. 7. 8.

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Diokno AC. Epidemiology and psychosocial aspects of incontinence. Urol Clin North Am 1995; 22:481– 485. FitzGerald MP, Brubaker L. Urinary incontinence symptom scores and urodynamic diagnoses. Neurourol Urodyn 2002; 21:30 – 35. Harvey MA, Kristjansson B, Griffith D, Versi E. The incontinence impact questionnaire and the urogenital distress inventory: a revisit of their validity in women without a urodynamic diagnosis. Am J Obstet Gynecol 2001; 185:25– 31. Nager CW, Schulz JA, Stanton SL, Monga A. Correlation of urethral closure pressure, leak-point pressure and incontinence severity measures. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12:395– 400. Patrick DL, Erickson P. Assessing health-related quality of life for clinical decision-making. In: Walker SR, Rosser RM, eds. Quality of Life Assessment: Key Issues in the 1990’s. Dordrecht: Kluwer Academic Publishers, 1993. Gill TM, Feinstein AR. A critical appraisal of the quality-of-life measurements. JAMA 1994; 272:619– 626. Tulsky DA. An introduction to test theory. Oncology 1990; 4:43– 48. Litwin MS, Lubeck DP, Henning JM, Carroll PR. Differences in urologist and patient assessments of health related quality of life in men with prostate cancer: results of the CaPSURE database. J Urol 1998; 159:1988 – 1992. Patrick DL, Deyo RA. Generic and disease-specific measures in assessing health care status and quality of life. Med Care 1989; 27(suppl):S217 – S232. Cronbach LJ. Coefficient alpha and the internal structure of tests. Psychometrika 1951; 16:297– 334. Nunnally JC. Psychometric Theory. New York: McGraw-Hill, 1978. Messick S. The once and future issues of validity: assessing the meaning and consequences of measurement. In: Wainer H, Braun HI, eds. Test Validity. Hillside, NJ: Lawrence Erlbaum Associates, 1988. Stewart AL, Greenfield S, Hays RD. Functional status and well-being of patients with chronic conditions. Results from the medical outcomes study. JAMA 1989; 262:907 – 913. Ware JE. SF-36 Health Survey: Manual and Interpretation Guide. Boston, MA: Health Institute, 1997. Kutner NG, Schechtman KB, Ory MG, Baker DI. Older adults’ perceptions of their health and functioning in relation to sleep disturbance, falling, and urinary incontinence. FICSIT Group. J Am Geriatr Soc 1994; 42:757– 762. Bergner M, Bobbitt RA, Carter WB, Gilson BS. The sickness impact profile: development and final revision of a health status measure. Med Care 1981; 19:787 – 805. Bergner M, Bobbitt RA, Pollard WE, Martin DP, Gilson BS. The sickness impact profile: validation of a health status measure. Med Care 1976; 14:57 –67. Hunt SM, McEwen J, McKenna SP. Measuring health status: a new tool for clinicians and epidemiologists. J R Coll Gen Pract 1985; 35:185 – 188. Thorpe AC, Cleary R, Coles J, Neal DE. Nottingham health profile measurement in the assessment of clinical outcome after prostatectomy. Northern regional prostate audit group. Br J Urol 1995; 76:446– 450. Hasan ST, Marshall C, Robson WA, Neal DE. Clinical outcome and quality of life following enterocystoplasty for idiopathic detrusor instability and neurogenic bladder dysfunction. Br J Urol 1995; 76:551 –557.

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Joly F, Brune D, Couette JE. Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer. Ann Oncol 1998; 9:751– 757. Hunskaar S, Vinsnes A. The quality of life in women with urinary incontinence as measured by the sickness impact profile. J Am Geriatr Soc 1991; 39:378 – 382. Grimby A, Milsom I, Molander U, Wiklund I, Ekelund P. The influence of urinary incontinence on the quality of life of elderly women. Age Ageing 1993; 22:82– 89. Corcos J, Beaulieu S, Donovan JL, Naughton M, Gotoh M. Quality of life assessment in men and women with urinary incontinence. J Urol 2002; 168:896– 905. Shumaker SA, Wyman JF, Uebersax JS, McClish D, Fantl JA. Health-related quality of life measures for women with urinary incontinence: the incontinence impact questionnaire and the urogenital distress inventory. Continence program in women (CPW) research group. Qual Life Res 1994; 3:291– 306. Beaulieu S, Collet JP, Tu LM, Macrammalla E, Wood-Dauphinee S, Corcos J. Performance of the incontinence impact questionnaire in Canada. Can J Urol 1999; 6:692– 699. FitzGerald MP, Kenton K, Shott S, Brubaker L. Responsiveness of quality of life measurements to change after reconstructive pelvic surgery. Am J Obstet Gynecol 2001; 185:20– 24. Moore KN, Jensen L. Testing of the incontinence impact questionnaire (IIQ-7) with men after radical prostatectomy. J Wound Ostomy Continence Nurs 2000; 27:304– 312. Robinson JP, Shea JA. Development and testing of a measure of health-related quality of life for men with urinary incontinence. J Am Geriatr Soc 2002; 50:935 – 945. Lubeck DP, Prebil LA, Peeples P, Brown JS. A health related quality of life measure for use in patients with urge urinary incontinence: a validation study. Qual Life Res 1999; 8:337– 344. Barber MD, Kuchibhatla MN, Pieper CF, Bump RC. Psychometric evaluation of 2 comprehensive condition-specific quality of life instruments for women with pelvic floor disorders. Am J Obstet Gynecol 2001; 185:1388 – 1395. Jackson S, Donovan J, Brookes S, Eckford S, Swithinbank L, Abrams P. The bristol female lower urinary tract symptoms questionnaire: development and psychometric testing. Br J Urol 1996; 77:805– 812. Temml C, Haidinger G, Schmidbauer J, Schatzl G, Madersbacher S. Urinary incontinence in both sexes: prevalence rates and impact on quality of life and sexual life. Neurourol Urodyn 2000; 19:259–271. Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to assess the quality of life of urinary incontinent women. Br J Obstet Gynaecol 1997; 104:1374 –1379. Black N, Griffiths J, Pope C. Development of a symptom severity index and a symptom impact index for stress incontinence in women. Neurourol Urodyn 1996; 15:630– 640. Patrick DL, Martin ML, Bushnell DM, Yalcin I, Wagner TH, Buesching DP. Quality of life of women with urinary incontinence: further development of the incontinence quality of life instrument (I-QOL). Urology 1999; 53:71– 76. Patrick DL, Martin ML, Bushnell DM, Marquis P, Andrejasich CM, Buesching DP. Cultural adaptation of a quality-of-life measure for urinary incontinence. Eur Urol 1999; 36:427– 435. Lee PS, Reid DW, Saltmarche A, Linton L. Measuring the psychosocial impact of urinary incontinence: the york incontinence perceptions scale (YIPS). J Am Geriatr Soc 1995; 43:1275– 1278. DuBeau CE, Kiely DK, Resnick NM. Quality of life impact of urge incontinence in older persons: a new measure and conceptual structure. J Am Geriatr Soc 1999; 47:989 – 994. Grimby A, Milsom I, Molander U, Wiklund I, Ekelund P. The influence of urinary incontinence on the quality of life of elderly women. Age Ageing 1993; 22:82– 89. Hagglund D, Walker-Engstrom ML, Larsson G, Leppert J. Quality of life and seeking help in women with urinary incontinence. Acta Obstet Gynecol Scand 2001; 80:1051 – 1055. O’Conor RM, Johannesson M, Hass SL, Kobelt-Nguyen G. Urge incontinence. Quality of life and patients’ valuation of symptom reduction. Pharmacoeconomics 1998; 14:531 – 539. Dugan E, Cohen SJ, Bland DR. The association of depressive symptoms and urinary incontinence among older adults. J Am Geriatr Soc 2000; 48:413 – 416.

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Penson and Litwin Melville JL, Walker E, Katon W, Lentz G, Miller J, Fenner D. Prevalence of comorbid psychiatric illness and its impact on symptom perception, quality of life, and functional status in women with urinary incontinence. Am J Obstet Gynecol 2002; 187:80– 87. Fultz NH, Herzog AR. Self-reported social and emotional impact of urinary incontinence. J Am Geriatr Soc 2001; 49:892– 899. Bo K, Talseth T, Vinsnes A. Randomized controlled trial on the effect of pelvic floor muscle training on quality of life and sexual problems in genuine stress incontinent women. Acta Obstet Gynecol Scand 2000; 79:598 – 603. Sand PK, Staskin D, Miller J. Effect of a urinary control insert on quality of life in incontinent women. Int Urogynecol J Pelvic Floor Dysfunct 1999; 10:100 –105. Versi E, Harvey MA. Efficacy of an external urethral device in women with genuine stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1998; 9:271 –274. Dmochowski RR, Davila GW, Zinner NR. Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence. J Urol 2002; 168:580 – 586. Naglie G, Radomski SB, Brymer C, Mathiasen K, O’Rourke K, Tomlinson G. A randomized, doubleblind, placebo controlled crossover trial of nimodipine in older persons with detrusor instability and urge incontinence. J Urol 2002; 167:586– 590. Woodman PJ, Misko CA, Fischer JR. The use of short-form quality of life questionnaires to measure the impact of imipramine on women with urge incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12:312 –315; discussion 315– 316. Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 2002; 187:40– 48. Bidmead J, Cardozo L, McLellan A, Khullar V, Kelleher C. A comparison of the objective and subjective outcomes of colposuspension for stress incontinence in women. Br J Obstet Gynaecol 2001; 108:408 –413. Morgan TO Jr, Westney OL, McGuire EJ. Pubovagin*l sling: 4-year outcome analysis and quality of life assessment. J Urol 2000; 163:1845 – 1848. Mukherjee K, Constantine G. Urinary stress incontinence in obese women: tension-free vagin*l tape is the answer. Br J Urol Int 2001; 88:881– 883.

5 Female Sexual Dysfunction Kathleen E. Walsh and Jennifer R. Berman Female Sexual Medicine Center, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.



Sexuality is one of the most important quality-of-life issues in both men and women. Societal, religious, family, and individual belief systems can significantly influence an individual’s sexuality. Female sexual dysfunction has been recognized as a common medical problem in all age groups. Basic science research in the anatomy and physiology of normal female sexual response and the pathophysiology of female sexual dysfunction has been limited. However, recent advances in understanding male sexual dysfunction and treatment options have facilitated interest in women’s health issues and the study of female sexual dysfunction. Sexual dysfunction is highly prevalent in both sexes, ranging from 25% to 63% of women and from 10% to 52% of men. Data from the National Health and Social Life Survey (NHSLS), a study of adult sexual behavior in the United States, found that sexual dysfunction (SD) is more prevalent in women (43%) than in men (31%). They also found an association between SD and various demographic characteristics, including age, education and race (1). In a study of 329 women, aged 18– 73, a standardized sexual function questionnaire identified 38.1% with anxiety or inhibition during sexual activity, 16.3% lacked sexual pleasure, and 15.4% had difficulty achieving org*sm (2). A survey of 448 women over the age of 60 found that 12% of married women had difficulty with intercourse and 14% experienced pain with intercourse. Two-thirds of the women surveyed were sexually inactive. Sexual activity was strongly correlated with marital status (3). In 1998, the American Foundation of Urologic Disease (AFUD) Consensus Panel classified female sexual dysfunction into 4 categories: desire, arousal, org*smic, and sexual pain disorders (4). 1. 2. 3. 4.

Hypoactive sexual desire disorder: the persistent or recurring lack of sexual fantasies/ thoughts and/or receptivity to sexual activity Sexual arousal disorder: the persistent or recurring inability to attain or maintain sufficient sexual excitement org*smic disorder: the persistent or recurring difficulty, delay in, or absence or attaining org*sm following sufficient sexual stimulation and arousal Sexual pain disorders: includes dyspareunia (genital pain with intercourse), vaginismus (involuntary muscle spasms of the outermost third of the vagin*), and other (genital pain caused by noncoital sexual stimulation) 65


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Pelvic floor disorders can also contribute to female sexual dysfunction. Disorders of the pelvic floor include incontinence, cystocele, rectocele, enterocele, and vagin*l and uterine prolapse. It is estimated that 10– 58% of adult women have symptoms of urinary incontinence (5). Studies have shown that urinary incontinence can be a significant contributing factor to female sexual dysfunction (6,7). Recent data have identified high rates of sexual dysfunction in patients with pelvic prolapse (8).



The definition of sexual dysfunction has included both psychological and physiological components. Masters and Johnson first characterized the female sexual response cycle in 1966 (9). The cycle consisted of four consecutive phases: excitement, plateau, org*smic, and resolution. Kaplan proposed a three-phase model in 1974, which included desire, arousal, and org*sm (10). Both of these cycles depict excitement or sexual desire as a spontaneous force that by itself stimulates sexual arousal. In contrast to these cycles, a five-phase model focusing on intimacy has been proposed by Basson (11) (Fig. 1). Basson suggests that for a large majority of women, the wish to enhance intimacy is the driving force of the female sexual response cycle. The cycle begins with basic intimacy needs, which may include mutuality, respect, and communication. When these needs are met, a woman will seek out and will be more receptive to sexual stimuli. The model hypothesizes a receptive type of desire, which stems from arousal and a woman’s conscious choice of sexual stimuli. If there is an overall positive emotional and physical interaction, the woman’s intimacy is enhanced and the cycle strengthened.



The medial preoptic, anterior hypothalamic, and related limbic-hippocampal regions are areas within the central nervous system that are responsible for sexual arousal. Once stimulated, these regions will emit signals to both the sympathetic and parasympathetic nervous systems.

Figure 1 Alternative model of the female sexual response cycle.

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Nonadrenergic/Noncholinergic Mediated Responses

Neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), nitric oxide synthetase (NOS), cyclic gyanylate monophosphate (cGMP), and substance P have all been identified in human vagin*l tissue nerve fibers (12,13). Recent studies suggest that nitric oxide (NO) and VIP are involved in altering vagin*l relaxation and secretory processes (14,15). In organ bath analysis of rabbit cl*toral cavernosal smooth muscle strips, enhanced relaxation was demonstrated in response to sodium nitroprusside and L-arginine (both NO donors). Using the same model, VIP was found to cause dose-dependent relaxation of cl*toral and vagin*l muscle (16). Phosphodiesterase type 5 (PDE5) has also been isolated in human cl*toral, vestibular, and vagin*l smooth muscle cultures (17,18). PDE5 is the enzyme responsible for degradation of cGMP and NO production. Sildenafil (Viagra), a PDE5 inhibitor, promotes intracellular cGMP synthesis and accumulation, thus allowing for enhanced relaxation of cl*toral and vagin*l smooth muscle (19). B.

Alpha-1-and Alpha-2-Adrenergic Responses

Alpha-adrenergic agents have been shown to be effective treatment for male erectile dysfunction. The adrenergic receptors associated with penile erection, libido, and erection are located in the male brain. Alpha-adrenergic mediators may also play a role in female sexual arousal (20). In preliminary organ chamber experiments using rabbit vagin*l tissue, exogenous norepinephrine (alpha-1 and alpha-2 agonist) was found to cause dose-dependent contraction of vagin*l smooth muscle. In addition, both alpha-1- (prazosin and tamsulosin) and alpha-2(delequamine) selective antagonists inhibit smooth muscle contraction (21). These findings suggest that adrenergic nerves mediate contractile response. There also appears to be a difference in the quality of contractile responses in upper and lower vagin*l segments, reflective of their different innervation and embryologic origin.





Only 1– 2% of total testosterone circulates unbound. The remainder is bound by sex hormone – binding globulin (SHBG) or albumin. The nonbound (free) testosterone is biologically active. Within the central nervous system, testosterone has been shown to affect female sexual behavior (22,23). Low levels of testosterone are associated with decreased sexual arousal, libido, sexual responsiveness, genital sensation, and org*sm (24,25). Recent evidence suggests that testosterone may help promote the expression of endothelial NOS, the enzyme responsible for production of NO (26). There is no direct regulator, stimulator, or feedback mechanism of androgen production in women. An increase in ovarian activity or adrenal activity has been shown to cause a rise in androgen production (27). Androgen deficiency in women can be caused by a number of factors including adrenal, pituitary, or ovarian surgery. Conditions such as hypopituitarism, adrenal insufficiency, anorexia nervosa, exercise-induced amenorrhea, and premature ovarian failure can also cause androgen deficiency. Lower androgen levels can occur in women taking exogenous corticosteroids and in women with chronic illness. Oral administration of hormones that elevate SHBG levels and reduce bioavailable androgens must also be considered to place women at risk of androgen deficiency. Increased levels of estradiol such as in the oral


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contraceptive pill or hormone replacement therapy (HRT) can increase SHBG, thus decreasing biologically available testosterone (28,29). Current commercial assays measuring total and free testosterone levels were developed to measure the much higher circulating concentrations in males. B.


Female sexual function is strongly influenced by estrogen. Both the neurological and vascular systems are affected by circulating levels of estrogen. In postmenopausal women, estrogen replacement was found to restore cl*toral and vagin*l vibration and pressure thresholds to levels to premenopausal levels (30). The vasoprotective and vasodilatory effects of estrogen have also been demonstrated. ERT has been shown to increase in vagin*l, cl*toral, and urethral arterial flow (31). Low estradiol levels are associated with thinning of mucosal epithelium, atrophy of vagin*l wall smooth muscle, and an increase in vagin*l pH. The less acidic environment within the vagin*l canal can lead to vagin*l infections, incontinence, urinary tract infections, and sexual dysfunction (32). Levels of estradiol ,50 pg/mL have been directly correlated with increased sexual complaints (33). Estrogen has also been shown to play a role in regulating vagin*l and cl*toral NOS (34). In animal models, aging and surgical castration are associated with decreased vagin*l and cl*toral NOS expression and apoptosis vagin*l smooth muscle and mucosal epithelium. Estrogen replacement restored vagin*l mucosal health, NO expression, and decreased vagin*l cell death (35). These findings suggest that medications such as sildenafil (Viagra), which increases levels of NO, may have a role in the treatment of female sexual dysfunction, in particular sexual arousal disorder.



Current evidence suggests that up to 80% of cases of sexual dysfunction have some organic component. Conditions associated with sexual dysfunction are listed in Table 1. A.


Males and females can experience sexual dysfunction secondary to diabetes, cardiovascular disease, hypertension, peripheral vascular disease, and tobacco use (36,37). Diminished blood flow of the iliohypogastric/pudendal arterial bed leads to significant compromise of the vascular bed in both male and female genitalia (38,39). In females this is termed cl*toral and vagin*l vascular insufficiency syndromes (40). Sufficient blood flow is crucial for maintaining vascular and muscular integrity, both components integral in sexual arousal. Diminished blood flow can lead to vagin*l wall and cl*toral smooth muscle fibrosis that can result in symptoms of vagin*l dryness and dyspareunia. Pelvic fractures, blunt trauma, surgical disruption, radiation, or chronic perineal pressure from bicycle riding can all lead to diminished vagin*l and cl*toral blood flow and sexual dysfunction. B.


In females, the most common causes of primary endocrine abnormalities are menopause, surgical or medical castration, premature ovarian failure, dysfunction of the hypothalamic/ pituitary axis, and chronic birth control use. The percentage of women with a primary endocrine

Female Sexual Dysfunction


Table 1 Medical Risk Factors Associated With Sexual Dysfunction Vascular Diabetes mellitus Atherosclerosis Hypertension Lipid disorders Peripheral vascular disease Hormonal Hypogonadism Hyperprolactinemia Hypo/hyperthyroidism Neurogenic Spinal cord injury Multiple sclerosis Musculogenic Pelvic floor muscle hyper/hypotonicity Medications (see Table 2) Psychogenic Depression Anxiety/obsession-compulsive disorder Social stressors Religious inhibitions Posttraumatic sexual experiences Dysfunctional attitudes about sex Other Autoimmune disorders Renal disease (dialysis) Bowel disease (colostomy) Bladder disease (incontinence, cystitis) Skin disorders (contact dermatitis, eczema)

dysfunction responsible for their sexual dysfunction is unknown. Estrogen and testosterone play a significant role in regulating female sexual function. There is a decline in both estrogen and testosterone levels with age, although the decline in testosterone is much less pronounced (28). A decrease in estrogen levels is associated with adverse neurovascular events affecting vagin*l, cl*toral, and urethral tissues. Low testosterone levels in females have been associated with a decline in sexual arousal, genital stimulation, libido, and org*sm. Therapy with combination estrogen-androgen compared with estrogen alone has shown to enhance libido, sexual desire and motivation, and overall sense of well-being (41). C.


Neurogenic sexual dysfunction can occur in both men and women with spinal cord injury (SCI) or disease of the central or peripheral nervous system. In a study comparing premenopausal women with SCI, ,50% of women with SCIs were able to achieve org*sm, compared with 100% of able-bodied women. They also reported that only 17% of women with complete lower


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motor neuron dysfunction affecting the S2 –S5 spinal segments were able to achieve org*sm, compared with 59% of women with other levels of SCI. Time to org*sm was also significantly increased in women with SCIs (42). Women with complete upper motor neuron injuries affecting sacral spinal segments had difficulty achieving psychogenic lubrication (43). Focus group studies examining diabetes and female sexuality identified complaints of increased fatigue, vaginitis, decreased sexual desire, decreased vagin*l lubrication, and an increased time to reach org*sm (44,45). D.


The levator ani and perineal membrane make up the pelvic floor musculature that influences female responsiveness during sexual activity. The perineal membrane consists of the bulbocavernous and ischiocavernosus muscles. These muscles contract both voluntarily and involuntarily, intensifying sexual arousal and org*sm. The levator ani muscles are involved in modulating motor responses during vagin*l receptivity and org*sm. Hypertonicity in the muscles can occur secondary to trauma (surgery, radiation, childbirth) and aging. This can cause vagin*l hypoanesthsia, coital anorg*smia, or urinary incontinence during sexual intercourse or org*sm. Hypertonicity of the levator ani muscles can cause sexual pain disorders such as vaginismus that leads to dyspareunia. E.


For many women who experience symptoms of sexual dysfunction, a combination of psychogenic and organic causes can be established. Psychogenic issues may include poor partner communication, performance anxiety, low self-esteem, social stressors, and religious inhibitions (46). Psychological disorders such as depression, posttraumatic sexual experiences, obsessive-compulsive disorder, or anxiety disorder can also have a significant impact on sexual function (47,48). F.


There are 1.5 billion prescriptions written every year in the United States. One or more new prescriptions are written in over two-thirds of physician office visits (49). While many prescription medications have been implicated in causing sexual dysfunction, antihypertensive, antidepressant, and antipsychotic medications are the most frequently cited (50). Controlled research is limited for the majority of medications and substances believed to cause female SD. Many articles present only subjective evidence or case reports. The classes of medications most commonly associated with causing sexual dysfunction are listed in Table 2.





Diagnosis of sexual dysfunction begins with sensitive and comprehensive questioning regarding sexual history. The Brief Index of Sexual Function in Women (BISF-W) is a validated 21-item, self-reported inventory of sexual interest, activity, satisfaction, and preference. This instrument can be used to differentiate among depressed, sexually dysfunctional, and healthy patients. This

Female Sexual Dysfunction


Table 2 Common Classes of Medications With Sexual Side Effects Class


Antihypertensive agents

Chemotherapeutic Central nervous system agents

Agents that affect hormones

a1 and 2 blockers (clonidine, reserpine, prasozin) b-blockers (metoprolol, propranolol) Calcium channel blockers (diltiazem, nifedipine) Diuretics (hydrochorothiazide) Alkylating agents (busulfan, chlorambucil, cyclophosphamide) Anticholinergics (diphenhyramine) Anticonvulsants (carbamazepine, phenobarbital, phenytoin) Antidepressants (MOAIs, TCAs, SSRIs)a Antipsychotics (phenothiazines, butyrophenones) Narcotics (oxycodone) Sedatives/anxiolytics (benzodiazepines) Antiandrogens (cimetidine, spironolactone) Antiestrogens (tamoxifen, raloxifene) Oral contraceptives


MAOIs, monoamine oxidase inhibitors; TCAs, tricylcic antidepressants; SSRIs, selective serotonin reuptake inhibitors.

subjective report from the patient is crucial to understanding whether or not psychotherapy and/ or medical therapy is useful. Studies have shown that physicians are reluctant to address sexual topics. The physicians cited several reasons including awkwardness with sex language, fear of insulting the patient, feeling uncomfortable with the topic, and not knowing what questions to ask or how to ask them (51,52). Evidence suggests, however, that patients believe sexual function is an appropriate topic and are relieved when it is discussed with their physician (53). Patients may feel pressure to live up to an idealized standard of performance and have unrealistic expectations for themselves or their partner. Many men and women question where they fit on the continuum from normality to dysfunction. Open-ended and/or direct questioning can help guide the physician and patient to understanding the patient’s sexual dysfunction.


Physical Exam

Every patient complaining of sexual dysfunction should undergo a thorough physical exam, including an external and internal gynecological exam. During the external gynecological exam, assessment of muscle tone, skin color, turgor and texture, and pubic hair distribution can identify conditions such as vaginismus, vulvar dystrophy, dermatitis, and atrophy. Examination of the posterior forchette and hymenal ring can help recognize episiotomy scars and possible strictures. The monomanual exam should include palpation of the rectovagin*l surface, levator ani, and bladder/urethra in order to identify any rectal disease, levator ani myalgia, vaginismus, urethritis, cystitis, or urinary tract infections. Cervical motion tenderness may indicate infection or peritonitis. Palpation of the uterus and adnexa are included in the bimanual exam and assist in the identification of uterine retrogression, fibroids, adnexal masses/cysts, and possible endometriosis. Finally, the speculum exam is utilized to evaluate for discharge, pH, vagin*l mucosa, Papanicolaou smear, and prolapse. In females, vagin*l pH, an indirect measurement of lubrication, can be measured using a digital pH probe. Decreased pulses, bruits, elevated blood


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pressure, and cool extremities are suggestive of vascular disease. Assessment should include a lipid profile and Doppler exams. The suggested baseline hormonal profile includes follicle-stimulating hormone (FSH), luteinizing hormone (LH), total and free testosterone levels, SHBG, and estradiol and prolactin levels. Measurements of FSH and LH can assist in evaluating for primary versus secondary hypogonadism. High levels of FSH and LH are indicative of primary gonadal failure, and low or normal levels suggest hypothalamic or pituitary disease. Decreased levels of estrogen and testosterone have been associated with decreased libido, decreased sensation, vagin*l dryness, dyspareunia, and decreased arousal. Hyperprolactemia can be seen in patients with decreased libido, galactorrhea, visual complaints, and headaches. Physical examination is positive for bitemporal hemianopsia. A CT or MRI may be needed to assess the pituitary gland. Fatigue and cold intolerance are seen in patients with hypothyroidism. Examination for a possible goiter, myxedema, dry skin, and coarse hair is warranted. An increased TSH and decreased free T4 are seen on laboratory tests. Hyperthyroidism can present with heat intolerance, weight loss, diaphoresis, and palpitations. Lid lag, exophthalamos, hyperreflexia, tremor, and tachycardia may be present on clinical exam. Laboratory values include a decreased TSH and an increased free T4. Cushing’s syndrome is diagnosed on clinical exam by easy bruising, weight gain, truncal obesity, “moon face,” “buffalo hump,” and striae. An elevated overnight dexamethasone suppression test is needed for confirmation of clinical exam. Diabetic patients should be evaluated for peripheral neuropathy, retinopathy, and abnormal body mass index. A thorough neurological exam is necessary in patients who have known or suspected SCI, nerve injury (prostate surgery, hysterectomy, childbirth), peripheral neuropathy, multiple sclerosis, or Parkinson’s disease. The neurologic exam may uncover sensory or motor impairment that will account for residual urine (neuropathic bladder) or incontinence. Since the bladder and its sphincter are innervated by the second to fourth sacral segments. Somatic function of the sacral cord levels S2 – 4 is assessed by touching the perianal skin or placing a finger in the patient’s rectum and noting contraction of the external anal sphincter muscles. This is termed the bulbocavernosus reflex.



In patients in whom an underlying medical condition has been diagnosed, treatment for correction or to control progression is appropriate. However, patients should be made aware that treatment of their condition does not guarantee the elimination of their sexual dysfunction. Consideration should be given to discontinuation of any medication suspected of contributing to sexual dysfunction or, if possible, switching to an alternative medication. For patients with a component of psychogenic dysfunction, referral to a psychologist or psychiatrist with expertise in sexual dysfunction may be beneficial.



Medical management of sexual dysfunction in women has focused on hormonal treatment. Both estrogen and testosterone are being used alone and in combination. In postmenopausal women, estrogen replacement has been found to improve cl*toral and vagin*l sensitivity, increase libido, restore vibratory and pressure thresholds, and decrease symptoms of vagin*l dryness and pain during intercourse (33,54). Estrogen is available in several forms including oral pill, dermal

Female Sexual Dysfunction


patch, vagin*l ring, and cream. The vagin*l ring is a therapeutic option for women with breast cancer who are unable to take oral or transdermal estrogen. Estrogen, especially when begun early in menopause, has been shown to be beneficial in the prevention and treatment of osteoporosis. ERT has also been shown to significantly reduce the risk for colon cancer, but not rectal cancers (55). Postmenopausal estrogen replacement, with or without progestin therapy, has a generally favorable impact on lipids, improves endothelial function, and has anti-inflammatory and antioxidant effects. However, the results of the Heart and Estrogen/Progestin Replacement Study (HERS) trial found no overall reduction in coronary events among women assigned to active hormone treatment. It is also suggested that there may be a transitory increase in coronary risk after starting hormone therapy in women with established coronary heart disease and a decreased risk thereafter (56). Prospective studies are under way to try to delineate how estrogen impacts Alzheimer’s disease. Potential risks of HRT include gallbladder disease, thromboembolism, and breast cancer. B.


Testosterone supplementation has been shown to improve mood and well-being in naturally menopausal and surgical postmenopausal women (41,57,58). Women treated with testosterone and intramuscular E2 were found to have improvements in sexual desire, fantasy, arousal, and org*sm (25,30,59). Decreased testosterone levels can be seen in women with premature ovarian failure and following natural, surgical or post-chemotherapy-induced menopause. For replacement purposes, testosterone is available in lozenger pill form, sublingual, dermal patch, and cream. Oral methyltestosterone is available in the United States either alone or in combination with estrogen (Estratest). In postmenopausal women who experience inhibited desire, dyspareunia, or lack of vagin*l lubrication, testosterone can be prescribed in combination with estrogen. The transdermal testosterone patch is under clinical investigation. The patches contain 150 mg testosterone. Two patches are applied simultaneously twice a week. Preliminary results have been promising (60,61). Testosterone topical cream has been approved for treatment of vagin*l lichen planus. Topical preparations can be make in 1%, 2%, and 3% formulations and can be applied up to three times per week. Benefits from testosterone therapy include improved libido, increased vagin*l and cl*toral sensitivity, increased vagin*l lubrication, and heightened arousal. Side effects of testosterone use that need to be monitored for in women include weight gain, cl*toral enlargement, increased facial hair, and hypercholesterolemia. Measurement of testosterone levels before and after therapy, lipid panels (cholesterol, triglyceride, HDL, LDL), and liver function tests are recommended (62,63). Whether or not testosterone therapy in premenopausal women is beneficial is under investigation. C.

Investigational Medications/Devices

Secondary to the increase in both clinical and biological research in female sexual dysfunction, several new investigational medications and devices are now available. See Table 3.



Female sexual dysfunction is a multicausal medical problem. Evaluation of the patient should include a comprehensive and collaborative effort between a physician and a psychologist.


Walsh and Berman

Table 3 Investigational Medications Treatment



Already used for

Side effects

Alista (cream)

Vivus Inc.

Topical Alprostadil/ PGE 1

Sexual arousal disorder

Transient burning in men; in trials in women now

Androsorb (cream)



Hormone booster for hypogonadal men

Early stages of clinical trial; may heighten libido in postmenopausal women



cl*toral therapy device

Arousal disorder

Increased sensation and blood flow to cl*tor*s via gentle suction

Estratest (pill)

Solvay Pharm.

Estrogentestosterone combination


Heightens libido in some women; side effects include acne and hair growth

Femprox (cream) NexMed, Inc.

Blood vessel dilator

Sexual arousal disorder

Improves blood flow to genitals; enhances arousal

Intrinsa (patch)

Proctor & Gamble Watson Labs


Hypoactive sexual desire disorder

Increases sexual activity and pleasure

Livial (pill)


Synthetic steroid

Osteoporosis, HRT

Approved in Europe for menopause symptoms; improved mood and libido



Arousal disorder Yohimbine African tree bark fortified with L-Argine

Increases vagin*l blood flow in postmenopausal women; may enhance arousal

Premarin or Estrace (cream)

Wyeth-Ayerst Warner Chilcott

Estrogen 17-b estradiol

Osteoporosis, vagin*l atrophy, HRT

vagin*l dryness and discomfort; not for use in women with history of blood clots or breast or endometrial cancer

SterylNorleucine VIP (cream)

Senetek PLC

Synthetic version of VIP

Arousal disorder

Enhances vagin*l lubrication, sensation, and genital engorgement

Testosterone (cream)

Off-label prescriptions from compounding pharmacies


New product

Not FDA approved; side effects include weight gain, hair growth, oily skin, enlarged cl*tor*s (continued )

Female Sexual Dysfunction Table 3.






Already used for

Side effects

Tostrelle (gel)



Hormone booster for hypogonadal men

Early study: testosterone levels in women on HRT jumped to levels of teenage girls

Uprima (pill)

Tap Pharm.


Sexual arousal disorder and low desire

Targets the brain and stimulates the release of dopamine; side effects: nausea, vomiting, not yet FDA approved


Pharmacia Upjohn


vagin*l atrophy

Improves dryness and irritation; not absorbed systemically

Vasofem (pill)


Blood vessel dilator

Sexual arousal disorder

Increases blood flow to genitals

Viagra (pill)


Blood vessel dilator

Male erectile dysfunction and female sexual arousal disorder

Increases blood flow to genitals; enhances arousal



Blood vessel Male erectile dilator, smooth dysfunction and muscle relaxer female sexual arousal disorder

Increases blood flow to genitals; enhances arousal

Although there are anatomic similarities between male and females, the complexity of female sexual dysfunction remains distinct from that of a man. The context in which a woman experiences her sexuality is equally as if not more important than the physiologic outcome she experiences. It is imperative that issues regarding how a woman views her sexuality be addressed before beginning medical therapy or determining treatment efficacies.


3. 4.

Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999; 281:537– 544. Rosen RC, Taylor JF, Leiblum SR, Bachmann GA. Prevalence of sexual dysfunction in women: results of a survey study of 329 women in an outpatient gynecological clinic. J Sex Marital Ther 1993; 19:171– 188. Diokno AC, Greiff V. Sexuality in older women. Arch Intern Med 1990; 150:197 – 200. Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy J, Goldstein I, Graziottin A, Heiman J, Laan E, Leiblum S, Padma-Nathan H, Rosen R, Segraves K, Segraves RT, Shabsigh R, Sipski M, Wagner G, Whipple B. Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J Urol 2000; 183:888– 893.

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Walsh and Berman Mallett VT, Bump RC. The epidemiology of female pelvic floor dysfunction. Curr Opin Obstet Gynecol 1994; 6:308 – 312. Bo K, Talseth T, Vinsnes A. Randomized controlled trial of the effect of pelvic floor muscle training on quality of life and sexual problems in genuine stress incontinent women. Acta Obstet Gynecol Scand 2000; 79:598 – 603. Hilton P. Urinary incontinence during sexual intercourse: a common, but rarely volunteered, symptom. Br J Obstet Gynaecol 1988; 95(4):377– 381. Berman JR, Raz S. Sexual dysfunction in women with pelvic prolapse [Abstract A2]. In: Program for Female Sexual Function Forum, Boston, MA, October 2001. Masters EH, Johnson VE. Human Sexual Response. Boston: Little Brown, 1966. Kaplan HS. The New Sex Therapy. London: Bailliere Tindall, 1974. Basson R. Using a different model for female sexual response to address women’s problematic low sexual desire. J Sex Marital Ther 2001; 27(5):395– 403. Hoyle CH, Stones RW, Robson T, Whitley K, Burnstock G. Innervation of vasculature and microvasculature of human vagin* by NOS and neuropeptide-containing nerves. J Anat 1996; 188:633– 644. Hsueh WA. Sexual dysfunction with aging and systemic hypertension. Am J Cardiol 1998; 61:18H– 23H. Burnett AL, Calvin DC, Silver RI, Peppas DS, Docimo SG. Immunohistochemical description of nitric oxide synthase isoforms in human cl*tor*s. J Urol 1997; 158:75 – 78. Helm G, Ottesen B, Fahrenkrug J. Vasoactive intestinal polypeptide in the human female reproductive tract: distribution and motor effects. Biol Reprod 1981; 25:227 – 234. Berman JR. VIP neurotransmitter in organ bath analysis of rabbit cl*toral cavernosal smooth muscle strips (unpublished data; in progress). Park K, Moreland RB, Goldstein I, Atala A, Traish A. Characterization of phosphodiesterase activity in human cl*toral corpus cavernosum smooth muscle cells in culture. Biochem Biophy Res Commun 1998; 249:612 –617. Traish A, Moreland RB, Huang YH, Kim NN, Berman J, Goldstein I. Development of human and rabbit vagin*l smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. Mol Cell Biol Res Commun 1999; (2):131 – 137. Min K, Kim NN, McAuley I, Stankowicz M, Goldstein I, Traish AM. Sildenafil augments pelvic nerve-mediated female genital sexual arousal in the anesthetized rabbit. Int J Impot Res 2000; 12(suppl 3):S32– S39. Meston CM, Heiman JR. Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychiatry 1998; 55:652 – 666. Berman JR. Alpha-1 (prazosin and tamsulosin) and alpha-2 (delequamine) selective antagonists inhibit smooth muscle contraction. (unpublished data; in progress). Hutchison JB, Steimer TH. Preoptic formation of 17b oestradiol is influenced by behavioural stimuli in the dove. Brain Res 1985; 360:366 – 369. Katz S, Morales AJ. Dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEAS) as therapeutic options in menopause. Semin Reprod Endocrinol 1998; 16:161 – 170. Rako S. The Hormone of Desire: The Truth About Testosterone, Sexuality and Menopause. New York: Three Rivers Press, 1999. Sherwin BB, Gelfand MM. Differential symptom response to parental estrogen and androgen in the surgical menopause. Am J Obstet Gynecol 1985; 151:153 – 160. Marin R, Escrig A, Abreu P, Mas M. Androgen-dependent nitric oxide release in rat penis correlates with levels of constitutive nitric oxide synthase isoenzymes. Biol Reprod 1999; 61:1012 – 1016. Rittmaster RS. Clinical relevance of testosterone and dihydrotestosterone metabolism in women. Am J Med 1995; 98(suppl 1A):17 – 21. Burger HG, Dudley EC, Hopper JL. The endocrinology of menopausal transition: a cross-sectional study of population-based sample. J Clin Endocrinol Metab 1995; 80:3537– 3547. Davis SR, Burger HG. Androgens and the postmenopausal woman. J Clin Endocrinol Metab 1996; 81:2759– 2764.

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Sarrel P, Dobay B, Wiita B. Estrogen and estrogen-androgen replacement in postmenopausal women dissatifisfied with estrogen-only therapy. Sexual behavior and neuroendocrine response. J Reprod Med 1998 43(10):847– 856. Sarrel PM. Ovarian hormones and vagin*l blood flow: using laser Doppler velocimetry to measure effects in a clinical trial of post-menopausal women. Int J Impot Res 1998; 10:S91 – S93. Caillouette JC, Sharp CF Jr, Zimmerman GJ, Roy S. vagin*l pH as a marker for bacterial pathogens and menopausal status. Am J Obstet Gynecol 1997; 176(6):1270 – 1275; discussion 1275– 1277. Sarrel PM. Sexuality and menopause. Obstet Gynecol 1990; 75(suppl 4):26S – 30S. Wyckoff MH, Chambliss KL, Mineo C, Yuhanna IS, Mendelsohn ME, Mumby SM, Shaul PW. Plasma membrane estrogen receptors are coupled to endothelial nitric-oxide synthase through Galpha(i). J Biol Chem 2001; 276:27071 – 27076. Berman JR, McCarthy MM, Kyprianou N. Effect of estrogen withdrawal on nitric oxide synthase expression and apoptosis in the rat vagin*. Urology 1998; 51:650 – 656. Benet AE, Melman A. The epidemiology of erectile dysfunction. Urol Clin North Am 1995; 22:699– 709. Kaiser FE, Korenman SG. Impotence in diabetic men. Am J Med 1988; 85:147 – 152. Morley JE, Korenman SG, Kaiser FE, Mooradian AD, Viosca SP. Relationship of penile brachial pressure index to myocardial infaction and cerebrovascular accidents in older men. Am J Med 1988; 84:445– 448. Park K, Goldstein I, Andry C, Siroky MB, Krane RJ, Azadzoi KM. Vasculogenic female sexual dysfunction: the hemodynamic basis for vagin*l engorgement insufficiency and cl*toral erectile insufficiency. Int J Impot Res 1997; 9(1):27 –37. Goldstein I, Berman JR. Vasculogenic female sexual dysfunction: vagin*l engorgement and cl*toral erectile insufficiency syndromes. Int J Impot Res 1998; 10(suppl 2):S84– S90; discussion S98– S101. Sherwin BB, Gelfand MM, Brender W. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Psychosom Med 1985; 47:339 –351. Sipski ML, Alexander CJ, Rosen RC. Sexual response in women with spinal cord injuries: implications for our understanding of the able-bodied. J Sex Marital Ther 1999; 25:11 – 22. Sipski ML. Sexual response in women with spinal cord injury: neurologic pathways and recommendations for the use of electrical stimulation. J Spinal Cord Med 2001; 24(3):155– 158. Le Mone P. The physical effects of diabetes on sexuality in women. Diabetes Educ 1996; 22(4):361– 366. Sarkadi A, Rosenqvist U. Contradictions in the medical encounter: female sexual dysfunction in primary care contacts. Fam Pract 2001; 18(2):161– 166. Meston, CM. The psychophysiological assessment of female sexual function. J Sex Educ Ther 2000; 25(1): 6 – 16. Aksaray G, Yelken B, Kaptanoglu C, Oflu S, Ozaltin M. Sexuality in women with obsessive compulsive disorder. J Sex Marital Ther 2001; 27(3):273– 277. Clayton AH. Recognition and assessment of sexual dysfunction associated with depression. J Clin Psychol 2001; 62(suppl 3):5– 9. Woosley RL, Flockhart D. A case for the development of Centers for Education and Research in Therapeutics (C.E.R.T.) Pharm Week 1995; 4(23):1 – 3. Finger WW, Lund M, Slagle MA. Medications that may contribute to sexual disorders. A guide to assessment and treatment in family practice. J Fam Pract 1997; 44(1):33 – 43. Lewis CE, Freeman HE. The sexual history-taking and counseling practice of primary care physicians. West J Med 1987; 147:165 – 167. Risen CB. A guide to taking a sexual history. Psychiatr Clin North Am 1995; 18:39 –53. Ende J, Rockwell S, Glasgow M. The sexual history in general medicine practice. Arch Intern Med 1984; 144:558 –561. Collins A. Landgren BM. Reproductive health, use of estrogen and experience of symptoms in postmenopausal women: a population based study. Maturitas 1994; 20(2):101– 111.

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Walsh and Berman Burkman RT, Collins JA, Greene RA. Current perspectives on benefits and risks of hormone replacement therapy. Am J Obstet Gynecol 2001; 185(suppl 2):S13 –S23. Khurana PS, Khurana C, Hsia J. Hormone replacement therapy for prevention of coronary heart disease: current evidence. Curr Atheroscler Rep 2001; 5:399– 403. Montgomery JC, Appleby L, Brincat M, Versi E, Tapp A, Fenwick PB, Studd JW. Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. Lancet 1987; 1:297 –299. Shifren JL, Braunstein GD, Simon JA, Casson PR, Buster JE, Redmond GP, Burki RE, Ginsburg ES, Rosen RC, Leiblum SR, Caramelli KE, Mazer NA. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N EngL J Med 2000; 343:682 –688. Davis SR, Tran J. Testosterone influences libido and well being in women. Trends Endocrinol Metab 2001; 12:33– 37. Javanbakht M, Singh AB, Mazer NA, Beall G, Sinha-Hikim I, Shen R, Bhasin S. Pharmaco*kinetics of a novel testosterone matrix transdermal system in healthy, premenopausal women and women infected with the human immunodeficiency virus. J Clin Endocrinol Metab 2000; 85:2395– 2401. Mazer NA. New clinical applications of transdermal testosterone delivery in men and women. J Control Release 2000; 65:303– 315. Berman LA, Berman JR, Chhabra S, Goldstein I. Novel approaches to female sexual dysfunction. Expert Opin Invest Drugs 2001; 10(1):85 – 95. Rako S. Testosterone supplemental therapy after hysterectomy with or without concomitant oophorectomy: estrogen alone is not enough. J Womens Health Gend Based Med 2000; 9:17– 23.

6 Hormonal Influence on the Lower Urinary Tract Dudley Robinson and Linda Cardozo King’s College Hospital, London, England



The female genital and lower urinary tract share a common embryological origin, arising from the urogenital sinus. Both are sensitive to the effects of female sex steroid hormones. Estrogen is known to have an important role in the function of the lower urinary tract throughout adult life, with estrogen and progesterone receptors demonstrated in the vagin*, urethra, bladder, and pelvic floor musculature (1 –4). This is supported by the fact that estrogen defiency occurring following the menopause is known to cause atrophic changes within the urogenital tract (5) and is associated with urinary symptoms such as frequency, urgency, nocturia, incontinence, and recurrent infection. These may also coexist with symptoms of vagin*l atrophy such as dyspareunia, itching, burning, and dryness. This chapter will review the role of estrogen and progesterone on lower urinary tract function in addition to assessing the role of estrogens in the management of lower urinary tract dysfunction.



The effects of the steroid hormone 17b-estradiol are mediated by ligand-activated transcription factors known as estrogen receptors. These are glycoproteins and share common features with both androgen and progesterone receptors and can be divided into several functional domains (6). The classic estrogen receptor (ERa) was first discovered by Jensen in 1958 and cloned from uterine tissue in 1986 (7), although it was not until 1996 that the second estrogen receptor (ERb) was identified (8). The precise role of the two different receptors remains to be elucidated although ERa appears to play a major role in the regulation of reproduction whilst ERb has a more minor role (9). Estrogen receptors have been demonstrated throughout the lower urinary tract and are expressed in the squamous epithelium of the proximal and distal urethra, vagin*, and trigone of the bladder (3,10), although not in the dome of the bladder, reflecting its different embryological origin. Pubococcygeus and the musculature of the pelvic floor have also been shown to be estrogen sensitive (11), although estrogen receptors have not yet been identified in the levator ani muscles (12). 79


Robinson and Cardozo

The distribution of estrogen receptors throughout the urogenital tract has also been studied, with both a and b receptors being found in the vagin*l walls and uterosacral ligaments of premenopausal women, although the latter were absent in the vagin*l walls of postmenopausal women (13). In addition, a receptors are localized in the urethral sphincter and when sensitised by estrogens are thought to help maintain muscular tone (14). In addition to estrogen receptors, both androgen and progesterone receptors are expressed in the lower urinary tract although their role is less clear. Progesterone receptors are expressed inconsistently, having been reported in the bladder, trigone, and vagin*. Their presence may be dependent on estrogen status (5). While androgen receptors are present in both the bladder and urethra, their role has not yet been defined (15). Interestingly, estrogen receptors have also been identified in mast cells in women with interstitial cystitis (16,17) and in the male lower urinary tract (18). More recently, the incidence of both estrogen and progesterone expression has been examined throughout the lower urinary tract in 90 women undergoing gynecological surgery; 33 were premenopausal, 26 postmenopausal without hormone replacement therapy (HRT), and 31 postmenopausal and taking HRT (19). Biopsies were taken from the bladder dome, trigone, proximal urethra, distal urethra, vagin*, and vesicovagin*l fascia adjacent to the bladder neck. Estrogen receptors were found to be consistently expressed in the squamous epithelia, although were absent in the urothelial tissues of the lower urinary tract of all women, irrespective of estrogen status. Progesterone receptor expression, however, showed more variability, being mostly subepithelial, and was significantly lower in postmenopausal women not taking oestrogen replacement therapy.



To maintain continence, the urethral pressure must remain higher than the intravesical pressure at all times except during micturition (20). Estrogens play an important role in the continence mechanism, with bladder and urethral function becoming less efficient with age (21). Elderly women have been found to have a reduced flow rate, increased urinary residuals, higher filling pressures, reduced bladder capacity, and lower maximum voiding pressures (22). Estrogens may affect continence by increasing urethral resistance, raising the sensory threshold of the bladder, or increasing a adrenoreceptor sensitivity in the urethral smooth muscle (23,24). In addition, exogenous estrogens have been shown to increase the number of intermediate and superficial cells in the vagin* of postmenopausal women (25). These changes have also been demonstrated in the bladder and urethra (26). More recently, a prospective observational study has been performed to assess cell proliferation rates throughout the tissues of the lower urinary tract (27). Fifty-nine women were studied of whom 23 were premenopausal, 20 were postmenopausal and not taking HRT, and 20 were postmenopausal and taking HRT. Biopsies were taken from the bladder dome, trigone, proximal urethra, distal urethra, vagin*, and vesicovagin*l fascia adjacent to the bladder neck. The squamous epithelium of oestrogen replete women was shown to exhibit greater levels of cellular proliferation than in those women who were estrogen deficient. Cyclical variations in the levels of both estrogen and progesterone during the menstrual cycle have been shown to lead to changes in urodynamic variables and lower urinary tract symptoms, with 37% of women noticing a deterioration in symptoms prior to menstruation (28). Measurement of the urethral pressure profile in nulliparous premenopausal women shows there is an increase in functional urethral length midcycle’ and early in the luteal phase corresponding to an increase in plasma estradiol (29). Furthermore, progestogens have been associated with an

Hormonal Influence on the Lower Urinary Tract


increase in irritative bladder symptoms (30,31) and urinary incontinence in those women taking combined hormone replacement therapy (32). The incidence of detrusor overactivity in the luteal phase of the menstrual cycle may be associated with raised plasma progesterone following ovulation, and progesterone has been shown to antagonize the inhibitory effect of estradiol on rat detrusor contractions (33). This may help to explain the increased prevalence of detrusor overactivity found in pregnancy (34). The role of estrogen replacement therapy in the prevention of ischemic heart disease has recently been assessed in a 4-year randomized trial, the Heart and Estrogen/Progestin Replacement Study (35). In the study 55% of women reported at least one episode of urinary incontinence each week, and were randomly assigned to oral conjugated estrogen plus medroxyprogesterone acetate or placebo daily. Combined HRT was associated with worsening stress and urge urinary incontinence, although there was no significant difference in daytime frequency, nocturia, or number of urinary tract infections. Finally, the role of estrogen therapy in the management of women with fecal incontinence has also been investigated in a prospective observational study using symptom questionnaires and anorectal physiological testing before and after 6 months of ERT. At follow-up, 25% of women were asymptomatic and a further 65% were improved in terms of flatus control, urgency, and fecal staining. In addition, anal resting pressures and voluntary squeeze increments were significantly increased following estrogen therapy, although there were no changes in pudendal nerve terminal latency. The authors conclude that estrogen replacement therapy may have a beneficial effect, although larger studies are needed to confirm these findings (36).



Urinary tract infection is also a common cause of urinary symptoms in women of all ages. This is a particular problem in the elderly, with a reported incidence of 20% in the community and .50% in institutionalized patients (37,38). Pathophysiological changes such as impairment of bladder emptying, poor perineal hygiene, and both fecal and urinary incontinence may partly account for the high prevalence observed. In addition, changes in the vagin*l flora due to estrogen depletion lead to colonization with gram-negative bacilli which in addition to causing local irritive symptoms also act as uropathogens. These microbiological changes may be reversed with estrogen replacement following the menopause, offering a rationale for treatment and prophylaxis.




Neurological Control

Sex hormones are known to influence the central neurological control of micturition, although their exact role in the micturition pathway has yet to be elucidated. Estrogen receptors have been demonstrated in the cerebral cortex, limbic system, hippocampus, and cerebellum (39,40), while androgen receptors have been demonstrated in the pontine micturition centre and the preoptic area of the hypothalamus (41). B.

Bladder Function

Estrogen receptors, although absent in the transitional epithelium at the dome of the bladder, are present in the areas of the trigone that have undergone squamous metaplasia (10). Estrogen is


Robinson and Cardozo

known to have a direct effect on detrusor function through modifications in muscarinic receptors (42,43) and by inhibition of movement of extracellular calcium ions into muscle cells (44). Consequently, estradiol has been shown to reduce the amplitude and frequency of spontaneous rhythmic detrusor contractions (45), and there is also evidence that it may increase the sensory threshold of the bladder in some women (46). C.


Estrogen receptors have been demonstrated in the squamous epithelium of both the proximal and distal urethra (10), and estrogen has been shown to improve the maturation index of urethral squamous epithelium (47). It has been suggested that estrogen increases urethral closure pressure and improves pressure transmission to the proximal urethra, both promoting continence (48 – 51). Additionally, estrogens have been shown to cause vasodilatation in the systemic and cerebral circulation, and these changes are also seen in the urethra (52 –54). The vascular pulsations seen on urethral pressure profilometry secondary to blood flow in the urethral submucosa and urethral sphincter have been shown to increase in size following estrogen administration (55), while the effect is lost following estrogen withdrawal at the menopause. The urethral vascular bed is thought to account for around a third of the urethral closure pressure, and estrogen replacement therapy in postmenopausal women with stress incontinence has been shown to increase the number of periurethral vessels (56). D.


Estrogen are known to have an effect on collagen synthesis, and they have been shown to have a direct effect on collagen metabolism in the lower genital tract (57). Changes found in women with urogenital atrophy may represent an alteration in systemic collagenase activity (58), and genuine stress incontinence and urogenital prolapse have been associated with a reduction in both vagin*l and periurethral collagen (59 –61). Furthermore, there is a reduction in skin collagen content following the menopause (62), with rectus muscle fascia being shown to become less elastic with increasing age, resulting in a lower energy requirement to cause irreversible damage (63). Changes in collagen content have also been identified, the hydroxyproline content in connective tissue from women with stress incontinence being 40% lower than in continent controls (64).




Urinary Incontinence

The prevalence of urinary incontinence is known to increase with age, affecting 15 –35% of community dwelling women over the age of 60 years (65) and other studies reporting a prevalence of 49% in women over 65 years (66). In addition, rates of 50% have been reported in elderly nursing-home residents (67). A recent cross-sectional population prevalence survey of 146 women aged 15– 97 years found that 46% experienced symptoms of pelvic-floor dysfunction defined as stress or urge incontinence, flatus or fecal incontinence, symptomatic prolapse, or previous pelvic-floor surgery (68). Little work has been done to examine the incidence of urinary incontinence, although a study in New Zealand of women over the age of 65 years found 10% of the originally continent developed urinary incontinence in the 3-year study period (69).

Hormonal Influence on the Lower Urinary Tract


Epidemiological studies have implicated estrogen deficiency in the etiology of lower urinary tract symptoms, with 70% of women relating the onset of urinary incontinence to their final menstrual period (5). Lower urinary tract symptoms have been shown to be common in postmenopausal women attending a menopause clinic, with 20% complaining of severe urgency and almost 50% complaining of stress incontinence (70). Urge incontinence in particular is more prevalent following the menopause, and the prevalence would appear to rise with increasing years of estrogen deficiency (71). There is, however, conflicting evidence regarding the role of estrogen withdrawal at the time of the menopause. Some studies have shown a peak incidence in perimenopausal women (72,73), while other evidence suggests that many women develop incontinence at least 10 years prior to the cessation of menstruation, with significantly more premenopausal women than postmenopausal women being affected (74). B.

Urogenital Atrophy

Urogenital atrophy is a manifestation of estrogen withdrawal following the menopause, and symptoms may appear for the first time more than 10 years after the last menstrual period (75). In addition, increasing life expectancy has led to an increasingly elderly population, and it is now common for women to spend a third of their lives in the estrogen-deficient postmenopausal state (76), with the average age of the menopause being 50 years (77). Postmenopausal women comprise 15% of the population in industrialised countries, with a predicted growth rate of 1.5% over the next 20 years. Overall, in the developed world 8% of the total population have been estimated to have urogenital symptoms (78), this representing 200 million women in the United States alone. It has been estimated that 10– 40% of all postmenopausal women are symptomatic (79), although only 25% are thought to seek medical help. In addition, two out of three women report vagin*l symptoms associated with urogenital atrophy by the age of 75 years (80). However, the prevalence of symptomatic urogenital atrophy is difficult to estimate since many women accept the changes as being an inevitable consequence of the aging process and thus do not seek help leading to considerable under reporting. A study assessing the prevalence of urogenital symptoms in 2157 Dutch women has been recently reported (81). Overall, 27% of women complained of vagin*l dryness, soreness, and dyspareunia, while the prevalence of urinary symptoms such as leakage and recurrent infections was 36%. When considering severity, almost 50% reported moderate to severe discomfort, although only a third had received medical intervention. Interestingly, women who had previously had a hysterectomy reported moderate to severe discomfort more often than those who had not. The prevalence of urogenital atrophy and urogenital prolapse has also been examined in a population of 285 women attending a menopause clinic (82). Overall, 51% of women were found to have anterior vagin*l wall prolapse, 27% posterior vagin*l prolapse, and 20% apical prolapse. In addition, 34% of women were noted to have urogenital atrophy, 40% complaining of dyspareunia. While urogenital atrophy and symptoms of dyspareunia were related to menopausal age, the prevalence of prolapse showed no association. However, while urogenital atrophy is an inevitable consequence of the menopause, women may not always be symptomatic. A recent study of 69 women attending a gynecology clinic were asked to fill out a symptom questionnaire prior to examination and undergoing vagin*l cytology (83). Urogenital symptoms were found to be relatively low and were poorly correlated with age and physical examination findings although not with vagin*l cytological maturation index. Women who were taking estrogen replacement therapy had higher symptom scores and physical examination scores.


Robinson and Cardozo

From this evidence it would appear that urogenital atrophy is a universal consequence of the menopause, although elderly women may be minimally symptomatic. Hence, treatment should not be the only indication for replacement therapy. VII. A.

MANAGEMENT OF LOWER URINARY DYSFUNCTION Estrogens in the Management of Incontinence

Estrogen preparations have been used for many years in the treatment of urinary incontinence (84,85), although their precise role remains controversial. Many of the studies performed have been uncontrolled observational series examining the use of a wide range of different preparations, doses, and routes of administration. The inconsistent use of progestogens to provide endometrial protection is a further confounding factor, making interpretation of the results difficult. To clarify the situation a meta-analysis from the Hormones and Urogenital Therapy (HUT) committee has been reported (86). Of 166 articles identified that were published in English between 1969 and 1992, only six were controlled trials and 17 were uncontrolled series. Meta-analysis found an overall significant effect of estrogen therapy on subjective improvement in all subjects and for subjects with urodynamic stress incontinence alone. Subjective improvement rates with estrogen therapy in randomized controlled trials ranged from 64% to 75%, although placebo groups also reported an improvement of 10 –56%. In uncontrolled series subjective improvement rates were 8 –89%, with subjects with urodynamic stress incontinence showing improvement of 34 –73%. However, when assessing objective fluid loss, there was no significant effect. Maximum urethral closure pressure was found to increase significantly with estrogen therapy, although this outcome was influenced by a single study showing a large effect (87). B.

Estrogens in the Management of Stress Incontinence

In addition to the studies included in the HUT meta-analysis, several authors have also investigated the role of estrogen therapy in the management of urodynamic stress incontinence only (Table 1). Oral estrogens have been reported to increase the maximum urethral pressures and lead to symptomatic improvement in 65– 70% of women (88,89), although other work has not confirmed this (90,91). More recently, two placebo-controlled studies have been performed examining the use of oral estrogens in the treatment of urodynamic stress incontinence in postmenopausal women. Neither conjugated equine estrogens and medroxyprogesterone (92)

Table 1 Summary of Randomized Controlled Trials Assessing the Use of Estrogens in the Management of Urinary Incontinence Study


Henalla et al. (87) Hilton et al. (96) Beisland et al. (95) Judge (120) Kinn and Lindskog (121) Samsioe et al. (97) Walter et al. (91) Walter et al. (122) Wilson et al. (90)

1989 1990 1984 1969 1988 1985 1978 1990 1987

Type of incontinence Stress incontinence Stress incontinence Stress incontinence Mixed incontinence Stress incontinence Mixed incontinence Urge incontinence Stress incontinence Stress incontinence



Conjugated estrogen Conjugated estrogen Estriol Quinestradol Estriol Estriol Estradiol and estriol Estriol Piperazine estrone sulfate

vagin*l vagin*l vagin*l Oral Oral Oral Oral Oral Oral

Hormonal Influence on the Lower Urinary Tract


nor unopposed estradiol valerate (93) showed a significant difference in either subjective or objective outcomes. Furthermore, a review of eight controlled and 14 uncontrolled prospective trials concluded that estrogen therapy was not an efficacious treatment for stress incontinence but may be useful for symptoms of urgency and frequency (94). From the available evidence estrogen does not appear to be an effective treatment for stress incontinence, although it may have a synergistic role in combination therapy. Two placebo-controlled studies have examined the use of oral and vagin*l estrogens with the a-adrenergic agonist phenylpropanolamine used separately and in combination. Both studies found that combination therapy was superior to either drug given alone, although while there was subjective improvement in all groups (95), there was only objective improvement in the combination therapy group (96). This may offer an alternative conservative treatment for women who have mild urodynamic stress incontinence. Estrogens have been used in the treatment of urinary urgency and urge incontinence for many years, although there have been few controlled trials to confirm their efficacy (Table 1). A double-blind placebo controlled crossover study using oral estriol in 34 postmenopausal women produced subjective improvement in eight women with mixed incontinence and 12 with urge incontinence (97). However, a double-blind multicenter study of the use of estriol (3 mg/d) in postmenopausal women complaining of urgency has failed to confirm these findings (98), showing both subjective and objective improvement but not significantly better than placebo. Estriol is a naturally occurring weak estrogen that has little effect on the endometrium and does not prevent osteoporosis although it has been used in the treatment of urogenital atrophy. Consequently, it is possible that either the dosage or route of administration in this study was not appropriate in the treatment of urinary symptoms, and higher systemic levels may be required. The use of sustained release 17b-estradiol vagin*l tablets (Vagifem, Novo Nordisk) has also been examined in postmenopausal women with urgency and urge incontinence or a urodynamic diagnosis of sensory urgency or detrusor overactivity. These vagin*l tablets have been shown to be well absorbed from the vagin* and to induce maturation of the vagin*l epithelium within 14 days (99). However, following a 6-month course of treatment, the only significant difference between active and placebo groups was an improvement in the symptom of urgency in those women with a urodynamic diagnosis of sensory urgency (100). A further double-blind, randomized, placebo-controlled trial of vagin*l 17b-estradiol vagin*l tablets has shown lower urinary tract symptoms of frequency, urgency, urge, and stress incontinence to be significantly improved, although no objective urodynamic assessment was performed (101). In both of these studies the subjective improvement in symptoms may simply represent local estrogenic effects reversing urogenital atrophy rather than a direct effect on bladder function. More recently a randomized, parallel-group, controlled trial has been reported comparing the estradiol-releasing vagin*l ring (Estring, Pharmacia, Uppsala, Sweden) with estriol vagin*l pessaries in the treatment of postmenopausal women with bothersome lower urinary tract symptoms (102). Low-dose vagin*lly administered estradiol and estriol were found to be equally efficacious in alleviating lower urinary tract symptoms of urge incontinence (58% vs. 58%), stress incontinence (53% vs. 59%), and nocturia (51% vs. 54%), although the vagin*l ring was found to have greater patient acceptability. To try to clarify the role of estrogen therapy in the management of women with urge incontinence, a meta-analysis of the use of estrogen in women with symptoms of “overactive bladder” has been reported by the HUT committee (103). In a review of 10 randomized placebocontrolled trials, estrogen was found to be superior to placebo when considering symptoms of urge incontinence, frequency, and nocturia, although vagin*l estrogen administration was found to be superior for symptoms of urgency. In those taking estrogens there was also a significant increase in first sensation and bladder capacity as compared to placebo.



Robinson and Cardozo

Estrogens in the Management of Recurrent Urinary Tract Infection

Estrogen therapy has been shown to increase vagin*l pH and reverse the microbiological changes that occur in the vagin* following the menopause (104). Initial small uncontrolled studies using oral or vagin*l estrogens in the treatment of recurrent urinary tract infection appeared to give promising results (105,106), although unfortunately this has not been supported by larger randomized trials. Several studies have been performed examining the use of oral and vagin*l estrogens although these have had mixed results (Table 2). Kjaergaard and colleagues (107) compared vagin*l estriol tablets with placebo in 21 postmenopausal women over a 5-month period and found no significant difference between the two groups. However, a subsequent randomized, double-blind, placebo-controlled study assessing the use of estriol vagin*l cream in 93 postmenopausal women during an 8-month period did reveal a significant effect (108). Kirkengen randomized 40 postmenopausal women to receive either placebo or oral estriol and found that although initially both groups had a significantly decreased incidence of recurrent infections, after 12 weeks estriol was shown to be significantly more effective (109). However, these findings were not confirmed subsequently in a trial of 72 postmenopausal women with recurrent urinary tract infections randomized to oral estriol or placebo. Following a 6-month treatment period and a further 6-month follow-up estriol was found to be no more effective than placebo (110). More recently a randomized, open, parallel-group study assessing the use of an estradiolreleasing silicone vagin*l ring (Estring; Pharmacia, Uppsala, Sweden) in postmenopausal women with recurrent infections has been performed which showed the cumulative likelihood of remaining infection free was 45% in the active group and 20% in the placebo group (111). Estring was also shown to decrease the number of recurrences per year and to prolong the interval between infection episodes.


Estrogens in the Management of Urogenital Atrophy

Symptoms of urogenital atrophy do not occur until the levels of endogenous estrogen are lower than that required to promote endometrial proliferation (112). Consequently, it is possible to use a low dose of estrogen replacement therapy in order to alleviate urogenital symptoms while avoiding the risk of endometrial proliferation and removing the necessity of providing endometrial protection with progestogens (113). The dose of estradiol commonly used in systemic estrogen replacement is usually 25 –100 mg, although studies investigating the use of estrogens in the management of urogenital symptoms have shown that 8 –10 mg of vagin*l estradiol is effective (114). Thus, only 10 – 30% of the dose used to treat vasomotor symptoms may be effective in the management of urogenital symptoms. Since 10 – 25% of women receiving systemic HRT still experience the symptoms of urogenital atrophy (115), low-dose local preparations may have an additional beneficial effect. A recent review of estrogen therapy in the management of urogenital atrophy has been performed by the HUT committee (116). Ten randomized trials and 54 uncontrolled series were examined from 1969 to 1995 assessing 24 different treatment regimens. Meta-analysis of 10 placebo-controlled trials confirmed the significant effect of estrogens in the management of urogenital atrophy (Table 3). The route of administration was assessed, and oral, vagin*l, and parenteral (transcutaneous patches and subcutaneous implants) were compared. Overall, the vagin*l route of administration was found to correlate with better symptom relief, greater improvement in cytological findings, and higher serum estradiol levels.

Route of delivery vagin*l tablets


vagin*l cream








Kjaergaard et al. 1990 (107) 21 postmenopausal women with recurrent cystitis 10 active group 11 placebo

Kirkengen et al. 1992 (109) 40 postmenopausal women with recurrent UTIs 20 active group 20 placebo

93 postmenopausal women with recurrent UTIs 50 active group 43 placebo

72 postmenopausal women with recurrent UTIs 36 active group 36 placebo

108 women with recurrent UTIs 53 active group 55 no treatment

Raz and Stamm 1993 (108)

Cardozo et al. 1998 (110)

Eriksen 1999 (111)


Study group

36 weeks for the active group 36 weeks or until first recurrence for the controls

6-month treatment period with a further 6 months follow-up

8 months

12 weeks

5 months

Duration of therapy

Cumulative likelihood of remaining free of infection was 45% in active group and 20% in control group (P ¼ .008).

Reduction in urinary symptoms and incidence of UTIs in both groups. Estriol no better than placebo.

Significant reduction in the incidence of UTIs in the group given estriol compared to placebo (P , .001).

Both estriol and placebo significantly reduced the incidence of UTIs (P , .05). After 12 weeks estriol was significantly more effective than placebo (P , .05).

Number of positive cultures not statistically different between the two groups.


Summary of Randomized Controlled Trials Assessing the Use of Estrogens in the Management of Recurrent Lower Urinary Tract Type of estrogen

Table 2

Hormonal Influence on the Lower Urinary Tract 87


Robinson and Cardozo

Table 3 Summary of Randomized Controlled Trials Assessing the Use of Estrogens in Urogenital Atrophy Study


Bellatoni et al. (123) Campbell et al. (124) Campbell et al. (124) Erikson and Ramussen (101) Felding et al. (125) Foidart et al. (126) Laufer et al. (127) Mettler and Olsen (113) Molander et al. (128) Raz and Stamm (108) Van der Linden et al. (129)

1991 1977 1977 1992 1992 1991 1983 1991 1990 1993 1993

Estrogen Estradiol Conjugated estrogen Conjugated estrogen Estradiol Estradiol Estriol Estradiol Estradiol Estriol Estriol Estriol

Route Transdermal Oral Oral Pessary Pessary vagin*l cream Transdermal Pessary Oral vagin*l cream Oral

With regard to the type of estrogen preparation estradiol was found to be most effective in reducing patient symptoms, although conjugated estrogens produced the most cytological change and the greatest increase in serum levels of estradiol and estrone. Finally, the effect of different dosages was examined. Low-dose vagin*l estradiol was found to be the most efficacious according to symptom relief, although oral estriol was also effective. Estriol had no effect on the serum levels of estradiol or estrone, while vagin*l estriol had minimal effect. vagin*l estradiol was found to have a small effect on serum estrogen, although not as great as systemic preparations. In conclusion, it would appear that estrogen is efficacious in the treatment of urogenital atrophy, and low-dose vagin*l preparations are as effective as systemic therapy. More recently, the use of a continuous low dose estradiol-releasing silicone vagin*l ring (Estring; Pharmacia, Uppsala, Sweden) releasing estradiol 5 –10 mg/24 h has been investigated in postmenopausal women with symptomatic urogenital atrophy (111). There was a significant effect on symptoms of vagin*l dryness, pruritis vulvae, dyspareunia, and urinary urgency with improvement being reported in .90% of women in an uncontrolled study; the maturation of vagin*l epithelium was also significantly improved. The patient acceptability was high, and while the maturation of vagin*l epithelium was significantly improved, there was no effect on endometrial proliferation. These findings were supported by a 1-year multicenter study of Estring in postmenopausal women with urogenital atrophy that found subjective and objective improvement in 90% of patients up to 1 year. However, there was a 20% withdrawal rate with 7% of women reporting vagin*l irritation, two having vagin*l ulceration, and three complaining of vagin*l bleeding although there were no cases of endometrial proliferation (117). Long-term safety has been confirmed by a 10-year review of the use of the estradiol ring delivery system that has found its safety, efficacy, and acceptability to be comparable to other forms of vagin*l administration (118). A comparative study of safety and efficacy of Estring with conjugated equine estrogen vagin*l cream in 194 postmenopausal women complaining of urogenital atrophy found no significant difference in vagin*l dryness, dyspareunia, or resolution of atrophic signs between the two treatment groups. Furthermore, there were similar improvement in the vagin*l mucosal maturation index and a reduction in pH in both groups, with the vagin*l ring being found to be preferable to the cream (119).

Hormonal Influence on the Lower Urinary Tract




Estrogens are known to have an important physiological effect on the female lower genital tract throughout adult life, leading to symptomatic, histological, and functional changes. Urogenital atrophy is the manifestation of estrogen withdrawal following the menopause, presenting with vagin*l and/or urinary symptoms. The use of estrogen replacement therapy has been examined in the management of lower urinary tract symptoms as well as in the treatment of urogenital atrophy, although only recently has it been subjected to randomized placebo-controlled trials and meta-analysis. Estrogen therapy alone has been shown to have little effect in the management of urodynamic stress incontinence, although when used in combination with an a-adrenergic agonists it may lead to an improvement in urinary leakage. When considering the irritive symptoms of urinary urgency, frequency, and urge incontinence, estrogen therapy may be of benefit, although this may simply represent reversal of urogenital atrophy rather than a direct effect on the lower urinary tract. The role of estrogen replacement therapy in the management of women with recurrent lower urinary tract infection remains to be determined although there is now some evidence that vagin*l administration may be efficacious. Finally, low-dose vagin*l estrogens have been shown to be have a role in the treatment of urogenital atrophy in postmenopausal women and would appear to be as effective as systemic preparations.

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Robinson and Cardozo Ulmsten U, Ekman G, Giertz G. Different biochemical composition of connective tissue in continent and stress incontinent women. Acta Obstet Gynaecol Scand 1987; 66:455. Diokno AC, Brook BM, Brown MB. Prevalence of urinary incontinence and other ueological symptoms in the non-institutionalised elderly. J Urol 1986; 136:1022. Yarnell J, Voyle G, Richards C, Stephenson T. The prevalence and severity of urinary incontinence in women. J Epidemiol Community Health 1981; 35:71 –74. Ouslander JG. Urinary incontinence in nursing homes. J Am Geriatr Soc 1990; 38:289 – 291. MacLennan AH, Taylor AW, Wilson AW, Wilson D. The prevalence of pelvic floor disorders and their relationship to gender, age, parity, and mode of delivery. Br J Obstet Gynaecol 2000; 107:1460 –1470. Kok AL, Voorhorst FJ, Burger CW, Van Houten P, Kenemans P, Jannsens J. Urinary and faecal incontinence in community residing elderly women. Age Ageing 1992; 21:211. Cardozo LD, Tapp A, Versi E, Samsioe G, Bonne Erickson P. The lower urinary tract in peri- and postmenopausal women. In: The Urogenital Defiency Syndrome. Bagsverd, Denmark: Novo Industri AS, 1987:10– 17. Kondo A, Kato K, Saito M. Prevalence of hand washing incontinence in females in comparison with stress and urge incontinence. Neurourol Urodyn 1990; 9:330 –331. Thomas TM, Plymat KR, Blannin J. Prevalence of urinary incontinence. BMJ 1980; 281:1243 –1245. Jolleys JV. Reported prevalence of urinary incontinence in a general practice. BMJ 1988; 296:1300 –1302. Burgio KL, Matthews KA, Engel B. Prevalence, incidence and correlates of urinary incontinence in healthy, middle aged women. J Urol 1991; 146:1255– 1259. Iosif CS. Effects of protracted administration of oestrol on the lower genitourinary tract in postmenopausal women. Acta Obstet Gynaecol Scand 1992; 251:115– 120. American National Institute of Health Population Figures. U.S. Treasury Dep. NIH. 1991. Research on the menopause in the 1990’s. Report or a WHO Scientific Group. In: WHO Technical Report Series 866. Geneva: WHO, 1994. Barlow D, Samsioe G, Van Greelan H. Prevalence of urinary problems in European countries. Maturitas 1997; 27:239 – 248. Greendale GA, Judd JL. The menopause: health implications and clinical management. J Am Geriatr Soc 1993; 41:426– 436. Samsioe G, Jansson I, Mellstrom D, Svanborg A. The occurrence, nature and treatment of urinary incontinence in a 70 year old population. Mauturitas 1985; 7:335 – 343. Van Geelen JM, Van de Weijer PH, Arnolds HT. Urogenital symptoms and resulting discomfort in non-institutionalised Dutch women aged 50 – 75 years. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11(1):9 – 14. Versi E, Harvey MA, Cardozo L, Brincat M, Studd JW. Urogenital prolapse and atrophy at menopause: a prevalence study. Int Urogynaecol J Pelvic Dysfunct 2001; 12(2):107– 110. Davila GW, Karapanagiotou I, Woodhouse S, Singh A, Huber K, Zimberg S, Seiler J. Are women with urogenital artophy syymptomatic? Obstet Gynaecol 2001; 97(4 suppl 1):S48. Salmon UL, Walter RI, Gast SH. The use of oestrogen in the treatment of dysuria and incontinence in postmenopausal women. Am J Obstet Gynaecol 1941; 14:23– 31. Youngblood VH, Tomlin EM, Davis JB. Senile urethritis in women. J Urol 1957; 78:150 – 152. Fantl JA, Cardozo LD, McClish DK, HUT. Committee. Oestrogen therapy in the management of incontinence in postmenopausal women: a meta-analysis. First report of the Hormones and Urogenital Therapy Committee. Obstet Gynaecol 1994; 83:12 –18. Henalla SM, Hutchins CJ, Robinson P, Macivar J. Non-operative methods in the treatment of female genuine stress incontinence of urine. Br J Obstet Gynaecol 1989; 9:222 –225. Caine M, Raz S. The role of female hormones in stress incontinence. In: Proceedings of the 16th Congress of the International Society of Urology, Amsterdam, Netherlands. Rud T. The effects of oestrogen and gestagens on the urethral pressure profile in urinary continent and stress incontinent women. Acta Obstet Gynaecol Scand 1980; 59:265 –270.

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Wilson PD, Faragher B, Butler B, Bullock D, Robinson EL, Brown ADG. Treatment with oral piperazine oestrone sulphate for genuine stress incontinence in postmenopausal women. Br J Obstet Gynaecol 1987; 94:568 – 574. Walter S, Wolf H, Barlebo H, Jansen H. Urinary incontinence in postmenopausal women treated with oestrogens: a double-blind clinical trial. Urology 1978; 33:135 – 143. Fantl JA, Bump RC, Robinson D. Efficacy of oestrogen supplementation in the treatment of urinary incontinence. Obstet Gynaecol 1996; 88:745 – 749. Jackson S, Shepherd A, Brookes S, Abrams P. The effect of oestrogen supplementation on postmenopausal urinary stress incontinence: a double-blind, placedo controlled trial. Br J Obstet Gynaecol 1999; 106:711 – 718. Sultana CJ, Walters MD. Oestrogen and urinary incontinence in women. Maturitas 1995; 20:129– 138. Beisland HO, Fossberg E, Moer A. Urethral insufficiency in post-menopausal females: treatment with phenylpropanolamine and oestriol separately and in combination. Urol Int 1984; 39:211– 216. Hilton P, Tweddel AL, Mayne C. Oral and intravagin*l oestrogens alone and in combination with alpha adrenergic stimulation in genuine stress incontinence. Int Urogynecol J 1990; 12:80 – 86. Samsicoe G, Jansson I, Mellstrom D, Svanberg A. Urinary incontinence in 75 year old women. Effects of oestriol. Acta Obstet Gynaecol Scand 1985; 93:57. Cardozo LD, Rekers H, Tapp A. Oestriol in the treatment of postmenopausal urgency: a multicentre study. Maturitas 1993; 18:47– 53. Nilsson K, Heimer G. Low does oestradiol in the treatment of urogenital oestrogen deficiency—a pharmaco*kinetic and pharamacodynamic study. Maturitas 1992; 15:121– 127. Benness C, Wise BG, Cutner A, Cardozo LD. Does low does vagin*l oestradiol improve frequency and urgency in postmenopausal women. Int Urogynaecol J 1992; 3(2):281. Eriksen PS, Rasmussen H. Low does 17b-oestradiol tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. Eur J Obstet Gynaecol Reprod Biol 1992; 44:137– 144. Lose G, Englev E. Oestradiol-releasing vagin*l ring versus oestriol vagin*l pessaries in the treatment of bothersome lower tract symptoms. Br J Obstet Gynaecol 2000; 107:1029 –1034. HUT Committee, 2001. Unpublished. Brandberg A, Mellstrom D, Samsioe G. Low dose oral oestriol treatment in elderly women with urogenital infections. Acta Obstet Gynaecol Scand 1987; 140:33 – 38. Parsons CL, Schmidt JD. Control of recurrent urinary tract infections in postmenopausal women. J Urol 1982; 128:1224– 1226. Privette M, Cade R, Peterson J. Prevention of recurrent urinary tract infections in postmenopausal women. Nephron 1988; 50:24 –27. Kjaergaard B, Walter S, Knudsen A. Treatment with low dose vagin*l oestradiol in postmenopausal women. A double blind controlled trial. Ugeskar Laeger 1990; 152:658– 659. Raz R, Stamm WE. A controlled trial of intravagin*l oestriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993; 329:753– 756. Kirkengen AL, Anderson P, Gjersoe E. Oestriol in the prophylactic treatment of recurrent urinary tract infections in postmenopausal women. Scand J Prim Health Care 1992; 10:142. Cardozo LD, Benness C, Abbott D. Low dose oestrogen prophylaxis for recurrent urinary tract infections in elderly women. Br J Obstet Gynaecol 1998; 105:403 – 407. Eriksen B. A randomised, open, parallel-group study on the preventitive effect of an oestradiolreleasing vagin*l ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol 1999; 180:1072– 1079. Samicore G. Urogenital ageing—a hidden problem. Am J Obstet Gynecol 1998; 178(5):S245– S249. Mettler L, Olsen PG. Long term treatment of atrophic vaginitis with low dose oestradiol vagin*l tablets. Maturitas 1991; 14:23 – 31. Smith P, Heimer G, Lindskog, Ulmsten U. Oestradiol releasing vagin*l ring for treatment of postmenopausal urogenital atrophy. Mauturitas 1993; 16:145– 154. Smith RJN, Studd JWW. Recent advances in hormone replacement therapy. Br J Hosp Med 1993; 49:799– 809.

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Robinson and Cardozo Cardozo LD, Bachmann G, McClish D, Fonda D, Birgerson L. Meta-analysis of oestrogen therapy in the management of urogenital atrophy in postmenopausal women: second report of the Hormones and Urogenital Therapy committee. Obstet Gynaecol 1998; 92:722– 727. Henriksson L, Stjernquist M, Boquist L, Cedergren I, Selinus I. A one-year multicentre study of efficacy and safety of a continuous, low dose, oestradiol-releasing vagin*l ring. (Estring) in postmenopausal women with symptoms and signs of urogenital aging. Am J Obstet Gynaecol 1996; 174:85– 92. Bachmann G. Oestradiol-releasing vagin*l ring delivery system for urogential atrophy. Experience over the last decade. J Reprod Med 1998; 43:991– 998. Ayton RA, Darling GM, Murkies AL. A comparative study of safety and efficacy of low dose oestradiol released from a vagin*l ring compared with conjugated equine oestrogen vagin*l cream in the treatment of postmenopausal vagin*l atrophy. Br J Obstet Gynaecol 1996; 103:351 –358. Judge TG. The use of quinestradol in elderly incontinent women: a preliminary report. Gerontol Clin 1969; 11:159 –164. Kinn AC, Lindskog M. Oestrogens and phenylpropanolamine in combination for stress incontinence in postmenopausal women. Urology 1988; 32:273 – 280. Walter S, Kjaergaard B, Lose G, Anderson JT, Heisterberg L, Jakobson H. Stress urinary incontinence in postmenopausal women treated with oral oestrogen (oestriol) and an a-adrenoceptor stimulating agent (phenylpropanolamine): a randomised double-blind placebo-controlled study. Int Urogynaecol J 1990; 1:74 – 79. Bellatoni MF, Harman SM, Cullins VE, Engelhardt SM, Blackman MR. Transdermal oestradiol with oral progestin: biological and clinical effects in younger and older postmenopausal women. J Gerontol 1991; 46:M216 – M222. Campbell S, Whitehead M, Oestrogen therapy and the menopausal syndrome. Clin Obstet Gynaecol 1977; 4:31– 47. Felding C, Mikkelse AL, Chausen HV, Loft A, Larson LG. Preoperative treatment with oestradiol in women scheduled for vagin*l operations for genital proplapse. A randomised double blind trial. Maturitas 1992; 15:241 – 249. Foidart JM, Vervliet J, Buytaert P. Efficacy of sustained release vagin*l formulation of oestriol in alleviating urogenital and systemic climeteric complaints. Maturitas 1991; 13:99– 107. Laufer LR, Defazio JL, Lu JKH. Oestrogen replacement therapy by transdermal oestradiol administration. Am J Obstet Gynaecol 1983; 146:533– 540. Molander U, Milson I, Ekelund P, Mellstrom D. An epidemiological study of urinary incontinence and related urogenital symptoms in elderly women. Maturitas 1990; 12:51– 60. Van der Linden MCGJ, Gerretsen G, Brandhurst MS, Doms ECM, Kremer CME, Doesburg WH. The effects of oestriol on the cytology of urethra and vagin* in postmenopausal women with genitourinary symptoms. Eur J Obstet Gynaecol Repord Biol 1993; 51:29 – 33.

7 Obstetric Issues and the Female Pelvis Roger P. Goldberg and Peter K. Sand Northwestern University, Evanston, U.S.A.



Urinary incontinence, anal incontinence, pelvic organ prolapse, and sexual dysfunction—the major disorders of the female pelvic floor—are associated with a substantial public health burden. And for many women, pregnancy, labor, and delivery represent the most important physiological events predisposing to these conditions. Although many aspects of obstetrical pelvic floor injury have yet to be fully understood, our knowledge of etiological mechanisms and epidemiological risk factors has markedly expanded over the past several years. This chapter will explore the effects of pregnancy and childbirth on the pelvic floor, and the impact of obstetrical events on these prevalent postreproductive disorders.




Evolutionary Strains and Anatomic Adaptations

From an evolutionary standpoint, certain anatomic trends have produced a maternal pelvic floor that is highly vulnerable to injury during pregnancy and childbirth. One factor was the increasing size of the newborn cranium to accommodate an enlarging brain, resulting in disproportion with the maternal pelvic outlet. With enhanced nutrition resulting in larger offspring, the maternal-fetal disproportion further increased. This trend was magnified by changes in locomotion and posture, as the upright bipedal stance (first adopted by the Australopithecines) shifted the pelvic outlet directly beneath the abdominopelvic contents. The female pelvis became increasingly foreshortened in the anterior-posterior plane, and laterally, more anterior and prominent ischial spines presented a further obstacle to delivery (1). The maternal pelvic floor can be viewed as an evolutionary response to these anatomical selection pressures—a transformation of vertically oriented “tail-wagging” muscles into a horizontal platform supporting the abdominopelvic organs. In the normal female pelvis, the major foundation consists of the paired levator ani muscles (2,3), whose position is maintained by endopelvic connective tissue and tone is preserved by nerves arising from the lumbosacral roots. All of these components—muscular anatomy, connective tissue supports, and nerve supply—are exposed to acute physical strains during childbirth, and also chronic wear and tear resulting from intraperitoneal forces. Pelvic floor dysfunction, in its various forms, can be viewed as a consequence of these conflicting demands. 95


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During pregnancy and delivery, both maternal and fetal adaptations serve to mitigate the full impact of anatomical strains on the maternal pelvis. On the fetal side, “molding” results in reduction of the fetal head circumference. On the maternal side, estrogen-mediated smooth muscle hypertrophy, connective tissue relaxation, and increased lubrication result in an accentuation of vagin*l length, skin thickness, and soft tissue compliance. Relaxin may be responsible for a variety of connective tissue changes within the bony pelvis, including increased mobility of the sacroiliac joint and pubic symphysis (4 – 6). Animal models have demonstrated relaxin-mediated collagen reorganization in the pubic symphysis (7). After the return of the nongravid hormonal milieu during the postpartum period, normal rigidity of the bony pelvis is resumed. Despite these and other compensatory adaptations, the potential for injury to the pelvic floor cannot be avoided even for “normal” childbirth. For nulliparas the first stage of labor may involve tissue compression for 20 or more. The second stage of labor, though substantially shorter, involves pressures between the fetal head and vagin*l wall averaging 100 mm Hg and reaching as high as 230 mm Hg. As a benchmark for comparison, consider that compressive forces of only 20 –80 mm Hg will cause blood perfusion to cease in the setting of orthopedic compartment syndrome, leading to permanent tissue damage if sustained. Unsurprisingly, obstetrical forces up to three times that intensity within the maternal pelvis, applied over many hours, may often result in physical sequelae. B.

Perineum and Anal Sphincter

In the nulliparous female the bulbocavernosis muscles, transverse perineal muscles, and anterior portion of the external anal musculature contribute to normal introital tone and anal sphincter pressure. Attenuation, widening or descent of the perineum after childbirth—whether resulting from episiotomy or a spontaneous injury—may result in bulging or laxity near the vagin* and rectum, loss of vagin*l sensation during intercourse, and/or anal incontinence. Perineal lacerations involving the anal sphincter have been reported in 10% of first vagin*l deliveries, and 0.3% of subsequent births (8). Apart from the presence or absence of perineal laceration, descent of the perineal plane relative the ischial tuberosities is common following vagin*l delivery and appears to correlate with anal sphincter dysfunction (9), but has the potential for resolving to the normal antenatal position in some women. Excessive descent of the perineal body during voluntary straining may represent a marker for persistent neuromuscular dysfunction after childbirth (10). However, the degree of perineal trauma evident after delivery has not been shown to accurately predict subsequent pelvic floor symptoms (11). One prospective study (12), using anal manometry in primiparous women prenatally and at 4– 6 weeks postnatally, found vagin*l delivery to be associated with significantly reduced squeeze pressure (SP: prenatal 269 cmH2O vs. postnatal 204 cmH2O; P ¼ .004). Cesarean section was not associated with any significant change in anal pressures. Thus, normal vagin*l deliveries with no evidence of sphincter injury are associated with a significant effect on postpartum anal function. External anal sphincter lacerations complicate up to 20% of vagin*l deliveries (13) and represent a major risk factor for reduced squeeze pressure (14) and anal incontinence, which will be subsequently reported in 4 – 50% of cases (8,15 – 20). Incontinence of flatus is reported six times more often by women who experienced anal sphincter injury during delivery (15). vagin*l delivery is independently associated with anal incontinence (21), and the risk is increased with prolonged labor, operative vagin*l delivery, and episiotomy (22). Although in the absence of a visible anal sphincter injury the incidence of subsequent anal incontinence is ,3%, a normal perineum on clinical examination does not exclude underlying anal sphincter damage (23).

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Postpartum endoanal ultrasound has demonstrated external anal sphincter defects in 20– 53% of women after normal vagin*l delivery (24 –28). Unfortunately, even a complete repair of visible anal sphincter lacerations, at the time of delivery, may be associated with suboptimal long-term results. According to postpartum ultrasonography, external anal sphincter separations can be detected in 11 –85% of cases after primary obstetrical repair of a sphincter injury (14,29). Among women with anal incontinence and a past history of repaired episiotomy or perineal laceration, up to 95% may have persistent external or internal anal sphincter defects visible by transanal ultrasound (30). Sixty-five percent of residual defects in this study were found in the mid or upper anal canal, suggesting an important role for internal anal sphincter injuries. The internal anal sphincter extends an additional 12 mm cranial to the external sphincter margin, is prone to disruption with severe perineal lacerations, and may be commonly overlooked during primary obstetrical repair (31). Using transanal ultrasonography, Sultan et al. (32) demonstrated internal anal sphincter lacerations in 17% of primiparas experiencing no visible perineal injury at the time of delivery. Posterior anal sphincter injuries, though far less common than anterior injuries, may also escape notice during perineal repair. Finally, neurological injury to the anal sphincter may play a role. Prolonged motor latencies may persist in the internal (upper) anal sphincter, for up to 5 months after vagin*l delivery (33). Denervation of the internal anal sphincter system after vagin*l delivery may persist even after the restoration of anal squeeze pressures, and may be associated with later development of fecal incontinence. Some surgeons advocate overlapping sphincteroplasty rather than end-to-end sphincter repair for the primary management of third- to fourth-degree perineal lacerations (34). Long-term outcomes following overlapping external anal sphincter repair are still being evaluated; however, recent case series have reported failure rates exceeding 50%, and the potential for decreased efficacy over time (35,36). Success rates appear to be lower among individuals with demonstrably abnormal pudendal nerve function preoperatively (16% vs. 62%) (37). Because of the limitations associated with the surgical repair of severe perineal injuries, primary prevention of obstetrical trauma should be regarded as the most effective approach for reducing the incidence of postreproductive perineal and anal sphincter dysfunction.


Effects of Episiotomy

Episiotomies were introduced from Europe during the early 1900s and have subsequently become the most common obstetrical operation. In the United States, 1.2 million are performed each year, with midline episiotomy performed in up to 60% of vagin*l deliveries (13). In decades past, the routine use of episiotomy was thought to provide an array of maternal benefits including preservation of pelvic muscle tone and sexual function, improved perineal healing, and a reduced risk of anal sphincter injury. Since then, however, a steadily growing number of observational studies support the conclusion that episiotomies increase rather than decrease the risk of pelvic floor dysfunction. Rectal injuries appear to be more often associated with than prevented by episiotomies, with the risk of anal sphincter laceration increasing by 1 –11%. Midline episiotomy in particular has been associated with a sharply elevated risk of severe lacerations into the vagin*, perineum, and rectum, in primiparous women (38 – 40). Mediolateral episiotomies confer only a 1 –2% likelihood of anal or rectal injury, but may be associated with a greater risk of postpartum and sexual pain. During second, third, or later deliveries, an even higher proportion of severe perineal injuries are preceded by episiotomy, though the absolute incidence is decreased in comparison to a first delivery.


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Episiotomies appear to be associated with slower recovery of pelvic floor muscle strength compared with an intact perineum after delivery and also spontaneous perineal lacerations (41,39). One Argentine study randomized .2000 women to undergo episiotomy either “routinely” or “selectively” if a significant perineal injury appeared to be imminent, and found pain and healing complications to be more common within the routine episiotomy group (42). Another randomized trial of selective episiotomy found that multiparous women in the selective group more often gave birth with an intact perineum (31% vs. 19%) (43). Nearly all perineal lacerations involving the anal sphincter were associated with midline episiotomy (46/47 in primiparous women and 6/6 among multiparous women). No differences were found between groups with respect to postpartum perineal pain, antepartum, and 3-month postpartum EMG perineometry, and urinary and pelvic floor symptoms. The authors concluded that restriction of episiotomy use among multiparous women results in significantly less perineal injury. With respect to anal incontinence, one retrospective cohort study (44) found midline episiotomy to be associated with an elevated risk of fecal incontinence at 3 (odds ratio 5.5) and 6 (3.7) months postpartum compared with women with an intact perineum. Compared with women with a spontaneous laceration in this cohort, episiotomy tripled the risk of fecal incontinence at 3 months (95% confidence interval 1.3 – 7.9) and 6 months (0.7 –11.2) postpartum, and doubled the risk of flatal incontinence at 3 months (1.3 – 3.4) and 6 months (1.2 –3.7) postpartum. The effects of episiotomy on sexual function have not been definitively established. One study demonstrated that at 3 months postpartum, sexual satisfaction appears to be highest among women without perineal injury, and lowest among women with an episiotomy that had extended during birth (39). A more recent study also found highest satisfaction among women with an intact perineum during delivery, but no difference between those who had undergone episiotomy or spontaneous perineal laceration (45). In summary, although selective episiotomies maintain a valid role in obstetrical management room, the scientific evidence does not support their routine use. A Cochrane report (46) concluded that the practice of routine episiotomy increases the overall risk of maternal trauma and complications during vagin*l delivery. Even during forceps or vacuum-assisted delivery, previously regarded as an absolute indication for episiotomy, the selective use of episiotomy has become increasingly common (47,48). The American College of Obstetricians and Gynecologists (ACOG) formally stated in March 2000 that routine episiotomy should not be considered a part of current obstetrical practice. D.

Levator Ani Muscles and Childbirth

The levator muscles represent the most important foundation of pelvic floor support, a broad muscular complex counteracting the constant downward force of the pelvic and abdominal organs. The iliococcygeous components form a shelflike barrier across the urogenital hiatus— supporting the uterus, vagin*, bladder, and other pelvic organs, and allowing the pelvic viscera to compress against a muscular floor rather than prolapsing through the urogenital hiatus with increased intra-abdominal pressure. The pubococcygeous and puborectalis muscles encircle the anal and urethral sphincters in the manner of a sling, augmenting intrinsic smooth muscle tone and maintaining tonic and phasic pressures. When intra-abdominal pressure is increased, reflex contraction of these muscular components contributes to urethral and anal sphincter tone, promoting continence. Injuries to the levator ani muscles and their nerve supply may, in many instances, represent the seminal obstetrical events ultimately leading to pelvic prolapse or urinary incontinence. Several forms of trauma to the levator ani may occur. Direct injury may include attenuation of the musculature, detachment of individual muscle components from their insertion points along

Obstetric Issues and the Female Pelvis


the pelvic sidewalls, or both. Indirect changes may involve generalized atrophy of the levator muscles resulting from pudendal neuropathy. Finally, diminished basal tone of the levator muscles may result in widening of the urogenital hiatus and descent of the levator plate from its horizontal position, thus orienting the pelvic viscera more directly over the widened urogenital hiatus (49) and shifting the burden of their support to connective tissues and ligaments. With cumulative intra-abdominal stress over time, weakening of these “secondary” endopelvic connective tissue supports may lead to pelvic organ prolapse (50) years after the initial neuromuscular insult. Diminished levator ani function after childbirth is common, but the severity of change varies according to the timing of postpartum assessment. Sampselle et al. (51) evaluated pelvic floor muscle strength using digital palpation before deliver and again at 3 months postpartum in a small cohort of primiparous women. Diminished levator strength was found to be associated with the onset of urinary stress incontinence. Peschers et al. (52) evaluated levator ani function before and after childbirth using intravagin*l perineometry, and found that pelvic muscle strength was significantly reduced 3– 8 days postpartum following vagin*l birth, but not after cesarean delivery, and returned to normal values within 2 months for most women. Allen and Hosker (53), using perineometry, also demonstrated a significant and persistent reduction in pelvic floor contraction strength. Prolonged EMG motor duration was associated with urinary incontinence postpartum, and appeared to be more likely after a long second stage of labor or vagin*l delivery of a macrosomic baby. E.

Pudendal Nerve and Neuropathic Changes

The majority of the important pelvic floor support structures, including the levator ani and sphincter muscles, receive their innervation from S2 –S4 anterior sacral nerve roots with motor branches coursing along the cranial surface of the pelvic floor. The pudendal nerve, arising from these same nerve roots, supplies the external anal and urethral sphincter, and perineum. Compression and stretching of the pudendal during childbirth appears to be a major risk factor associated with diminished levator muscle function afterwards. With delayed conduction, the slinglike components of the levator complex, such as the pubococcygeous muscle, may fail to reflexively contract and elevate sphincter pressure during a cough or sneeze. Basal tone of the shelflike levator plate and perineal body, as previously mentioned, may also diminish as a result of neuropathic changes. The pudendal nerve and its three branches supply most of the anatomic structures helping to maintain pelvic support and continence—including the perineum and vagin*, levator muscle complex, and anus. Stretching and compression of the pudendal nerve appears to be particularly vulnerable as the fetus descends past the ischial spine in the midpelvis. Apart from the pudendal nerve, a recent cadaveric study by Barber et al. (54) suggested that the levator ani musculature may receive substantial innervation from independent “levator nerve” components arising from the lumbosacral nerve roots. In 1986, Snooks and Swash (55) reported that partially reversible pudendal nerve injury occurs commonly with vagin*l birth. Pudendal nerve terminal motor latency measurements indicate decreased conduction in women with vagin*l birth compared with nulliparous controls, an effect that appears to be prevented by cesarean delivery (114). The likelihood of nerve injury is increased by forceps delivery, multiparity, increased duration of the second stage of labor, third-degree perineal tear, and macrosomia (53,56). Pelvic floor neuromuscular function can also be measured by concentric needle electromyography or singlefiber electromyography, providing a quantitative measure of pelvic floor denervation. Denervation changes within the pubococcygeous and striated anal sphincter muscles have been observed following 42 –80% of vagin*l deliveries (55). While some degree of


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reinnervation by surrounding nerves will frequently occur, loss of muscle function is common. Evidence of denervation injury appears to increase with parity, and can be demonstrated 5– 6 years after delivery (57,58). Cesarean delivery appears to effectively prevent denervation injuries when performed electively, but does not confer full protection if performed after the onset of labor. For many women, pelvic neuropathy will have no clinical consequences; for others, these nerve injuries initiate a pathophysiologic cascade eventually leading to incontinence, prolapse, and pelvic floor dysfunction. Women with stress incontinence have delayed pudendal conduction relative to controls on motor latency testing. Increased pudendal nerve terminal motor latency has been associated with genuine urinary stress incontinence. (59,60) and lower maximal urethral closure pressure (60) compared to asymptomatic controls. However, electromyography of the urethral sphincter has not demonstrated increased denervation among stress-incontinent subjects (61) and has also failed to correlate sphincter denervation with a reduction in urethral closure pressures (62). Smith et al. (63) showed that partial denervation of the pelvic floor after childbirth is associated with both genital prolapse and urinary incontinence. A 5-year follow-up by Snooks et al. (58) demonstrated that denervation-reinnervation patterns on electromyography may become more pronounced over time, and indicate higher risks of urinary and fecal incontinence. Others have found anal incontinence to be associated with pelvic floor neuropathy in 75– 80% of cases (64,65). Among multiparas, levator denervation appears to be more common among those with prolapse, according to histological and electromyelographic study, occurring in up 50% of women with symptomatic pelvic organ prolapse (66,67). To what extent these changes to the levator ani musculature represent a direct cause of pelvic organ prolapse, or its consequence, is not fully certain. In summary, pelvic floor neuropathy is a common repercussion of childbirth—less often recognized than vagin*l and perineal injury, but arguably more significant with respect to the etiology of subsequent pelvic floor dysfunction. Our understanding of the mechanisms of neuromuscular injury, and its repercussions, continues to evolve. F.

Connective Tissues, Ligaments, and Bony Pelvis

Some element of injury to the connective tissues of the pelvic floor is inevitable during childbirth. And in the etiology of pelvic floor disorders after childbirth, endopelvic connective tissue injuries have an established role (68). Investigations into the etiology and treatment of pelvic organ prolapse have sought to identify “site-specific” breaks and detachments of the endopelvic connective tissue from their anatomical insertion sites, as the origins for pelvic organ prolapse (69). These include paravagin*l defects in the anterior vagin*l compartment, sitespecific defects in the rectovagin*l (Denonvillier’s) fascia, and ligamentous/fascial detachments of the vagin*l apex. Attenuation injuries to the endopelvic connective tissue during childbirth may account for a variety of other forms of prolapse, including central cystoceles, rectoceles, and uterine prolapse resulting from laxity of the uterosacral ligaments. Bony pelvic anatomy may have an important relationship to the progress of childbirth, the physical ease or difficulty encountered during childbirth, and the amount of pressure, stretch, and potential injury to the soft-tissue structures of the pelvic floor. Among the pelvic shapes described in the 1930s, the “gynecoid” pelvis is most common among women, and also best suited for childbirth owing to its generous anterior-posterior and lateral dimensions with a wide pubic arch. “Android” features present a greater challenge for vagin*l delivery and may exist to some degree in up to 24% of women undergoing x-ray pelvimetry before labor (70). The relatively narrow pubic arch, prominent ischial spines, and anterior-posterior foreshortening resulting from the protuberant sacrum create a heart-shaped passageway. The “anthropoid”

Obstetric Issues and the Female Pelvis


pelvis resembles a narrow oval, restricted laterally by convergent sidewalls and prominent spines. “Platypoid” pelvises resemble a horizontal oval, and are the least commmon shape in the female population. Although it remains unclear which specific bony pelvic features signal a higher risk of pelvic floor injury, certain shapes would seem, at least in theory, to be of potential significance. For instance, a narrow pubic arch (android, anthropoid) may indicate less anterior space for the fetal vertex, and thus a greater likelihood of posterior injury to the perineum and anal sphincter. A wide pubic arch (gynecoid, platypoid) or prominent coccyx may force the fetal head from posterior to anterior, increasing the risk of compression injury to the bladder and urethra. Finally, in the case of a narrow midpelvic region due to prominent ischial spines or convergent pelvic sidewalls (anthropoid), the pudendal nerves may be exposed to an increased risk of compression near Alco*ck’s canal. However, these potential “pelvic factors” in maternal injury have not been scientifically evaluated. Spinal anatomy may also influence the risk of pelvic prolapse according to one case control study of 92 women. When compared with patients with a normal curvature, patients with an abnormal spinal curvature were 3.2 times more likely to have development of pelvic organ prolapse (71). A loss of lumbar lordosis appeared to be the most significant risk factor in the development of pelvic organ prolapse. Another matched observational study of bony pelvic anatomy concurred that women with advanced uterovagin*l prolapse have less lumbar lordosis and a pelvic inlet that is oriented less vertically than women without prolapse (72). The impact of specific pelvic shapes on postreproductive pelvic floor dysfunction, and the proper role of pelvic anatomy assessment in obstetrical decision making, warrants future investigation.



The symptom of stress urinary incontinence occurs in 32– 85% of pregnant women, peaking in the third trimester (73 –75). Francis showed an intrapartum prevalence of 85% in multiparas and 53% in nulliparas, with nearly half of these patients noting some degree of incontinence before the observed pregnancy. Several other investigators have observed that stress incontinence, arising with pregnancy and childbirth, may often fail to resolve. Stanton et al. (76) prospectively studies 181 women in the third trimester and through the puerperium. Of the 83 nulliparas, 38% had stress incontinence during the third trimester and 6% had persistent postpartum incontinence. Among 98 multiparas, 10% had stress incontinence symptoms prior to pregnancy, 42% had stress incontinence in the third trimester, and 11% had persistent postpartum incontinence. Meyer et al. (77) examined 149 women during pregnancy, and again at 9 weeks postpartum. The rates of stress urinary incontinence were 31% and 7%, respectively, meaning that 22% of patients with stress incontinence during pregnancy had persistence after delivery. Several investigators have observed that mode delivery may have a profound impact on the persistence of incontinence for the long term. Viktrup et al. (73) prospectively studied urinary incontinence symptoms before, during, and after pregnancy in 305 primiparous women. The multivariate analysis identified the length of second stage, fetal head circumference, episiotomy, and birth weight as risk factors for postpartum stress incontinence, whereas cesarean section was protective against incontinence. Among women with stress incontinence during pregnancy, 21 of 167 women (13%) had persistent incontinence postpartum compared to none of the 35 delivered by cesarean (P , .05). At 3 months postpartum, only 4% of these women had persistent stress incontinence complaints; after 1 year, only 3% still had stress incontinence. In subsequent pregnancies, however, it appears that these patients are at greater risk for more severe incontinence with earlier onset and persistence beyond the puerperium. And in a 5-year follow-up study, Viktrup and Lose (78) questioned 278 of the 305 women (91%) comprising


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their original cohort, and found a 30% prevalence of stress incontinence. Nineteen percent of women who were not incontinent in the original trial developed stress incontinence in the ensuing 5 years. Again, cesarean section was found to significantly decrease the risk of stress incontinence. The proper role of elective cesarean delivery, for preventing urinary incontinence, remains uncertain. Iosif and Ingemarsson (1) showed that stress urinary incontinence does occur following elective cesarean delivery, but to a much lesser degree than after vagin*l birth. Among 204 of 264 women who had undergone an elective cesarean section 1– 6 years earlier, 4.7% had persistent stress urinary incontinence after primary cesarean section, and 4.1% after a second cesarean section. Several mechanisms may contribute to the relationship among pregnancy, childbirth, and urinary incontinence. An increased prevalence of urethral hypermobility is one important change (79,80) known to be associated with genuine stress urinary incontinence. Peschers and colleagues (81) studied the anatomic effects of vagin*l delivery and found that bladder neck support was significantly weaker after vagin*l delivery than following cesarean section (P , .001) or compared to a group of 25 nulliparous controls (P , .001). They also found that bladder neck descent during Valsalva was significantly increased after vagin*l delivery compared to cesarean section in both primiparous and multiparous women (P , .001). Diminished intrinsic urethral function, immediately after childbirth or later on also plays an important role in the development of genuine stress incontinence (82). Van Geelen et al. (83) demonstrated an association between vagin*l delivery and decreased urethral closure pressure and functional length; the absence of these changes after cesarean delivery highlights the importance of birth mode rather than only pregnancy. Meyer et al. (77), in a prospective study of 149 women, found similar changes in functional urethral length, and intravagin*l and intra-anal pressure, 9 weeks after vagin*l delivery compared to antepartum values. None of these changes were found in the 33 women who had delivered by cesarean. As previously mentioned, vagin*l delivery can produce neurological changes in the pelvic floor, adversely affecting pudendal nerve conduction velocity, vagin*l contraction strength, and urethral closure pressure. Presumably, these alterations may account for persistent or new-onset genuine stress incontinence in women after vagin*l delivery. After cesarean section, these pathophysiological changes are far less pronounced. Whether or not pelvic floor damage leading to persistent stress urinary incontinence is cumulative for multiparous women—“from delivery to delivery”—has been controversial. Mallett et al. (84) demonstrated that absolute parity and further childbearing did not further influence pelvic floor neurophysiology, and concluded that most pudendal nerve damage occurs during the first vagin*l delivery. Hojberg et al. (85) studied 1781 primiparas at 16 weeks’ gestation and showed an odds ratio of 5.7 for stress incontinence after vagin*l delivery compared to 1.3 with cesarean delivery. Within their cohort, the first vagin*l delivery was a major risk factor for developing urinary incontinence; subsequent deliveries did not increase the risk significantly. However, other population-based observational studies and prospective trial have shown strong associations between vagin*l delivery and increasing parity with stress incontinence. Persson et al. (86) studies 10,074 women in Sweden having surgery for stress incontinence and found a strong association with stress incontinence and parity, and also that the odds ratio of prior cesarean section versus vagin*l delivery was 0.21. Moller et al. (87) studie 502 women with lower urinary tract symptoms and 742 controls. They found an association of parity and stress incontinence with an odds ratio of 2.2 after one vagin*l delivery, 3.9 after a second vagin*l delivery, and 4.5 after a third delivery. Marshall et al. (88) studied 7771 women early in the pueperium and found a strong association between parity and stress incontinence. A 1989 consensus conference of the National Institutes of Health identified parity as an established risk factor for urinary incontinence (89).

Obstetric Issues and the Female Pelvis




From the standpoint of pelvic injury a great number of obstetrical complications of previous generations are now fully preventable. Obstetrical fistulae, for instance, are today exceedingly rare due to the recognition and prevention of obstructed labor. Unfortunately, the more commonplace pelvic floor disorders—urinary incontinence, anal incontinence, and pelvic prolapse—remain largely overlooked. It could be argued that pelvic floor disorders are natural consequences of childbirth just as skin cancer is a natural consequence of sun exposure. Both are associated with identifiable risk factors, both can affect quality of life greatly, and both, in many cases, are preventable. During and after pregnancy, strategies for reducing the risk of subsequent pelvic floor dysfunction should be considered.


During Pregnancy


Pelvic Floor Exercises, Perineal Massage, and General Health

Daily pelvic floor exercises may consist of 20 –30 daily repetitions throughout pregnancy. Increased muscle “reserve” before delivery may help to decrease the risk of injury during childbirth and accelerate healing afterward. Improved muscular tone, and awareness of muscular location, may enhance the patient’s ability to voluntarily relax the pelvic floor musculature during labor and delivery. Two controlled trials of antenatal pelvic floor exercises have demonstrated reduced urinary stress incontinence postpartum, but no discernible differences in pelvic muscle strength according to perineometry (90,91). Prenatal pelvic floor exercises may reduce the likelihood of incontinence symptoms after delivery (90). Perineal massage represents another strategy for the prevention of obstetrical injury, which involves gentle stretching of the lubricated perineum in preparation for delivery. The protective effects of perineal massage remain a subject of debate, with some investigators concluding no benefit when performed only during labor (92). However, two studies of perineal massage begun during the third trimester have reported a decreased risk of perineal laceration. One found that among women aged 30 or older, massage increased the chances of an intact perineum by 12%. Another study, involving over 1500 women, found that for those without a previous vagin*l birth, 3 weeks of perineal massage routine increased the likelihood of an intact perineum by 9% (93). A follow-up analysis (94) 1 year later reported on subsequent symptoms within the same cohort; among women with a previous vagin*l birth, perineal massage reduced the odds of perineal pain at 3 months postpartum from 94% to 86%. For women without a previous vagin*l birth, no differences were found between the two groups. Maintaining a moderate exercise routine during pregnancy, and optimal body weight, may reduce the strain of pregnancy and childbirth on the pelvic floor. One study demonstrated that although transient urinary incontinence during pregnancy improving postpartum is common, persistent leakage is more likely among women gaining more weight before delivery. Excess body weight has been identified as a risk factor for postpartum stress urinary incontinence and urgency (95), with a body mass index .30 conferring an elevated risk (96). A reasonable target for weight gain is 2 – 4 pounds during the first trimester and 1 pound per week thereafter, translating into 25 –35 pounds for a full-term pregnancy. For women who are overweight before pregnancy, significantly less weight gain is acceptable. Exercise during pregnancy should be tailored to specific consideration, including changes in posture, balance, and coordination; altered respiratory patterns; increased joint and ligament mobility due to relaxin; and increased vulnerability of the pelvic floor beneath the gravid uterus.


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Finally, preventing constipation is an important cornerstone for minimizing pelvic floor strain during pregnancy, as gastrointestinal motility decreases owing to the effects of progesterone and iron supplementation. Maintaining regular bowel movements, with proper consistency, helps to reduce straining with defecation and thus reduces stress on the pelvic floor supports. Dietary fiber should be accompanied by adequate hydration, regular exercise, and stool softeners. 2.

Predicting Pelvic Floor Injury: Maternal and Fetal Factors

Predicting the ease or difficulty of childbirth, and forecasting which women are at highest risk for pelvic floor dysfunction, has challenged physicians and midwives for centuries. In the 1940s, for instance, some obstetricians maintained that a large number of abdominal striae indicated an increased risk of pelvic injury. More recently, double-jointed fingers and distensible skin have been implicated as markers for generalized connective tissue disorders predisposing to pelvic floor dysfunction. Specific demographic factors may have an impact on the risk of pelvic floor injury. One report of .50,000 women, from the University of Miami, found maternal age might relate to be predictive of severe lacerations involving the anal sphincter or rectum; older women during their first delivery were found to be most at risk, especially with delivery of a large baby (97). Within a cohort to African mothers, women ,150 cm tall were more likely to experience cephalopelvic disproportion leading to a failed labor. Short stature (,10th centile) within this group was associated with a twofold risk of cesarean delivery, and 15 times the usual risk of requiring forceps or vacuum assistance. Urethral and bladder neck hypermobility, defined by transvagin*l ultrasound before delivery, has also been associated with an elevated risk of postpartum incontinence (98). Fetal head engagement may influence the relationship between childbirth and the pelvic floor. For nulliparous women, engagement before the onset of labor is regarded as an indicator of good maternal-fetal “fit.” Conversely, a lack of fetal head engagement at term may reflect cephalopelvic disproportion and higher risk for arrest of labor. One study assessed .1200 women carrying their first pregnancy, demonstrating that the risk of cesarean section nearly tripled if fetal head engagement had not yet occurred at the start of active labor (99). Another study found that lack of fetal head engagement was associated with both a longer second stage of labor and an elevated risk of cesarean, from 6.9% to 27%. Other studies have reported equal success at achieving vagin*l delivery even if the fetal head is floating above the pelvic inlet. The relationship of fetal engagement to the maternal pelvic floor, and postreproductive body, remains uncertain. If an unengaged fetus portends a longer labor, more physical effort, or greater odds of an operative delivery, it could represent a risk factor for subsequent pelvic floor dysfunction. Pelvimetry during pregnancy or labor has been used to help determine the most important features of the bony pelvis. Unfortunately, pelvimetry—whether performed clinically or with radiological imaging—has not been found to reliably predict the course of labor and delivery, or obstetrical pelvic injury. Forecasting pelvic floor injuries and postreproductive problems based on pelvic shape remains a medical area posing more questions than answers. B.

During Labor and Delivery

During the second stage of labor, many elements of childbirth are viewed as inevitable. But in fact, a number of important decisions may have implications for subsequent pelvic floor function. Recognizing modifiable risk factors for pelvic floor injury is an important aspect of routine obstetrical care.

Obstetric Issues and the Female Pelvis



Pushing Positions and Techniques

Whereas some women will be instructed to push immediately after reaching “full” cervical dilatation, others will be advised to wait until feeling the strong urge created by fetal descent, and still others are encouraged to wait until the urge is unbearable. Determining the most appropriate technique and time parameters for second stage from the standpoint of the maternal pelvic floor—and the relative impact of “active” versus “passive” laboring—remains an area of women’s health warranting attention. “Full dilatation,” after all, refers exclusively to the cervix; from the standpoint of the major pelvic floor supports, an enormous degree of tissue dilatation has yet to occur for most women. It has been suggested that premature active pushing before full cervical dilatation may create sever stress against the pelvic floor, by advancing the cervix and its surrounding attachments ahead of the fetal vertex (100). Lithotomy is the most common position used by women choosing regional analgesia, with the lower extremities held fully flexed and abducted during each contraction. Although some practitioners suspect that the “uphill” orientation of this pushing style may increase the difficulty of delivery, specific disadvantages for pelvic floor function have not been proven. Squatting is purported to increase the diameter of the pelvic outlet compared with the lyingdown position, and help to shift the tail bone posteriorly. Studies have shown reduced rates of forceps delivery and perineal lacerations compared with semirecumbent position (101). One study of 300 women (102) showed squatting to be associated with a decreased risk of perineal laceration and episiotomy. The effects of squatting on the deeper pelvic floor supports are unknown. Other, less common delivery positions may have a positive or negative impact on the pelvic floor. Sitting has been associated with more rapid delivery; however, studies evaluating birthing chairs have shown perineal swelling and labial lacerations to be more likely, and blood loss increased. Lateral positioning (“side lying”) may be useful for multiparous women with an already relaxed introitus, by improving control over the speed of fetal expulsion at the end of second stage, and thereby helping to avoid perineal injury caused by a precipitous delivery. Upright positioning has been advocated as a means to shorten the duration of labor and reduce the need for forceps or vacuum assistance. Randomized trials have found the upright position to be associated with lower rates of perineal injury, postpartum pain, and risk of undergoing episiotomy compared with lithotomy (103). A Cochrane analysis concluded similar benefits of upright or lateral, compared with supine, positioning (104). The upright, sitting, and squatting positions should be avoided if significant perineal swelling develops. Finally, the “hands and knees” position may help to correct fetal malposition—for instance, rotation from occiput posterior, which has been associated with higher rates of anal sphincter injury (105). This position may also help to shift the pressure of the fetal vertex from posterior to anterior, if an imminent perineal injury appears likely. Management of the “final push,” at the time of fetal crowning, may occasionally take on significance to pelvic floor injury, with shallow breathing and pelvic relaxation, rather than straining, allowing the fetal head to ease gradually past the introitus. There is evidence that the common hands-on approach, including counterpressure against the fetal head and “guarding” of the perineum with the practitioner’s second hand, may be of little benefit to preventing perineal injury (106). Hyperflexion of the lower extremities may increase the risk of a sudden laceration as the fetal head rapidly distends the perineum, and should therefore be avoided in most cases. 2.

Second-Stage Labor Strategies

Directed Valsalva pushing starting at full cervical dilatation is the most common second-stage labor strategy, its advocates arguing that the duration of labor grows too long in the absence of a


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constant maternal expulsive effort, introducing more stress for the baby and a greater likelihood of maternal neuromuscular injury. Critics of active pushing, on the other hand, maintain that it shortens labor and delivery less than is often assumed while increasing maternal exhaustion, stressing the pelvic floor supports, and possibly increasing the risk for pelvic injury. Among primigravid women, active pushing for .1 h has been shown to confer an increased risk of pudendal neuropathy and denervation injury; however, prolonging the passive (nonpushing) second stage may not increase the risk of injury. “Delayed” pushing involves resisting the urge to push, while allowing the fetus to passively descend past the pelvic supports. One 1998 randomized controlled trial of delayed pushing demonstrated a nonsignificant trend with fewer instrumental vagin*l deliveries. More recently, a multicenter study (107) conducted at 12 different sites throughout Canada, Switzerland, and the United States evaluated a delayed pushing strategy among 1862 nulliparous women, all with epidural analgesia, randomized to either immediate pushing at full dilatation or delayed pushing for up to 2 h before pushing. “Difficult deliveries” were less likely in the delayed pushing group, and forceps assistance was less often necessary. The benefits of delayed pushing were greatest for women whose fetus was at a high station, or in the occiput posterior position, when full cervical dilatation was determined. Notably, the 41% episiotomy rate in this study may limit the external validity of its conclusions. A more recent randomized controlled trial of delayed pushing found no increase in adverse events, despite prolongation of second stage of up to 4.9 h (108). “Physiologic” (or “spontaneous”) pushing is similar to the delayed pushing approach, entailing the delay of expulsive efforts until the onset of an overwhelming physical urge. A 1999 survey compared spontaneous to directed pushing and found that advanced perineal lacerations were less likely, and an intact perineum more likely, in the “spontaneous pushing” group (109). A randomized trial of 350 women in Denmark found no differences between women “actively” or “spontaneously” pushing, with respect to perineal injury or duration of labor (110). A shorter active (pushing) phase and less maternal fatigue have also been cited as potential benefits (111). The effects of pushing styles on pelvic floor function are largely unknown. Increased terminal nerve motor latency may be associated with a longer pushing stage. One study (112) evaluated the effect of pushing time on anal function, comparing primiparous women with a second stage shorter than 2 h to those with a second stage exceeding 3 12 h. The “long labor” group had a significantly higher rate of new-onset flatal incontinence (73% vs. 44%). Finally, in some cases a prolonged active second stage may predispose to maternal exhaustion. If this results in a greater likelihood of operative delivery by forceps or vacuum, the increased risk for pelvic floor injury resulting from these interventions should be recognized. 3. Impact of Operative vagin*l Delivery: Forceps and Vacuum Eighty years ago, episiotomies and forceps were routine elements of childbirth and were advocated, until recently, as a means to avoid pelvic injury and provide a more “controlled” delivery. However, the majority of existing research has debunked this viewpoint, and today it is widely accepted that operative delivery tends to increase rather than decrease the risk of perineal injury, and often has a negative impact on other pelvic floor structures (113). Although vacuum and forceps procedures retain a valuable role in obstetrical care, they should not be routinely performed. Forceps delivery markedly increases the risk of third- and fourth-degree lacerations (114) and also pelvic neuropathy—perhaps not surprising, since the average force of forceps against the surrounding pelvic tissues has been estimated at 75 psi. Up to 80% of women who undergo forceps delivery will have anal sphincter injuries detectable by transanal ultrasound

Obstetric Issues and the Female Pelvis


(25). Forceps also confer an elevated risk of urinary incontinence. Within one cohort, the odds of stress incontinence 7 years after childbirth were shown to be 10 times higher among women with a previous forceps delivery (115). A prospective study evaluating the incidence of new-onset urinary incontinence after forceps and vacuum delivery compared with spontaneous vagin*l delivery found that in primiparous women, urinary incontinence after forceps delivery is more likely to persist compared with spontaneous vagin*l or vacuum delivery (116). At 6 months postpartum, the relative risk of urinary incontinence after forceps has been estimated as 1.5 compared to spontaneous vagin*l delivery (117). Women after forceps delivery have significantly weaker levator and anal strength than those who had a spontaneous vagin*l birth (118). Vacuum-assisted deliveries accounted for almost 6% of all deliveries in 1995. Although vacuum application is not appropriate for all operative deliveries, there is evidence to suggest that, compared with forceps, vacuum delivery is generally associated with lower rates of pelvic trauma (119 – 121). Studies randomizing operative deliveries to either forceps or vacuum have demonstrated lower rates of severe perineal lacerations, and anal injury, for the latter (122). One 1999 study randomized women undergoing operative delivery to one of these two instruments, and found that anal sphincter injury was significantly more common after forceps (79% vs. 40%). Anal incontinence was also more common after forceps delivery (32% vs. 16%). The incidence of occult anal sphincter injury is also increased after forceps, compared with vacuum delivery (123). A Cochrane report concluded that vacuum delivery is associated with significantly less risk of perineal injury compared with forceps (124).


Physical Effects of Macrosomia

Macrosomia is associated with a variety of potential fetal problems, including birth trauma, shoulder dystocia, and lower Apgar scores. However, it is important not to overlook the potential maternal complications including higher rates of spontaneous perineal injury and episiotomies, increased nerve damage detected by EMG (53), an increased risk of perineal injuries involving the anorectum (40,125 –127), pudendal nerve injury (128), and significantly weaker anal squeeze pressures postpartum (129). vagin*l delivery of one or more babies weighing at least 4000 g raises the risk of long-term stress incontinence (130). Larger infants have been linked to a 60% increase in the risk of an episiotomy at delivery (131). Newborn head circumference has been demonstrated as an independent risk factor for third-degree perineal injury during childbirth (132).


Multiple Pregnancy and Childbirth: Effects on the Pelvic Floor

The effects of multiple gestation on pelvic floor injury, and postreproductive problems such as incontinence, prolapse, and sexual dysfunction, were recently investigated (133). Among 733 mothers of multiples, with a mean age of 40 years, substantial rates of pelvic floor symptoms were reported, including urinary stress incontinence by 45%, flatal incontinence by 28%, fecal soiling among 12%, and fecal incontinence by 9.6%. A subanalysis of obstetrical risk factors found that avoiding vagin*l delivery resulted in a 50% reduction in the risk of urinary incontinence, even after controlling for age, total parity, and body mass index. As the prevalence of multiple gestation continues to increase in the modern obstetrical landscape, the risk factors influencing the maternal pelvic floor, and the most rational strategies for the prevention of significant injuries, need to be more precisely defined.



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Other Factors: Fetal Position and Analgesia

Fetal position may also have prognostic significance for the effects of labor and delivery on the pelvic floor. The occiput posterior fetal position, for instance, has been long associated with childbirth that is more prolonged, and sometimes more painful, based on anecdotal experience. One study from Ireland (134) validated these observations, analyzing a large number of deliveries and comparing babies descending in the posterior and anterior positions. Occiput posterior deliveries were associated with less favorable outcomes, including an increased incidence of anal sphincter injuries, and higher rates of delivery by cesarean and forceps. Fewer than half of occiput posterior deliveries ended in a spontaneous vagin*l birth. Another study found similar results, including higher rates of perineal injury and episiotomy (135). The effects of epidural analgesia on the maternal pelvis have also been investigated. Some investigators claim that epidurals may help to relax the pelvic floor musculature, facilitating a smoother and less traumatic delivery. Others express concern that by producing a sensory blockade, epidurals may increase the risk for stalled labor, leading to higher rates of forceps or cesarean delivery and thus greater risks for pelvic floor injury. The potential effects of epidurals on perineal injury were evaluated in a 1995 retrospective analysis (136). Within this sample of nulliparous women, severe perineal lacerations occurred in 16% of women receiving epidurals versus only 9.7% in women without one. Further analysis of this cohort, however, indicated that this difference was the result of more frequent episiotomy and operative (forceps and vacuum) assistance within the epidural group. Thus, avoiding these interventions whenever possible— rather than avoiding the epidural per se—appeared to be the important principle for preventing obstetrical pelvic floor injury. Other studies examining the effect of epidurals on pelvic floor injury (137) have found no differences with respect to intrapartum trauma.



Opinions and attitudes regarding the appropriate use of cesarean section for the prevention of pelvic injury vary widely. According to a 1996 survey of obstetricians published in the Lancet (138), 31% of female obstetricians report that if faced with a normal full-term pregnancy, they would personally select cesarean over vagin*l delivery. Remarkably, 80% of these individuals cited concern over perineal injury as the main rationale. Another survey of female gynecologists reported, somewhat more modestly, that 16% would personally choose cesarean delivery for delivery of their own full-term, nonmacrosomic infant; most respondents, again, cited a desire to prevent incontinence and pelvic prolapse. A survey of 135 midwives, in contrast, found that only 6% would choose cesarean to protect their pelvic floor. Whether this reflects the fact that midwives provide care only to women before and during childbirth—and not years later, when the majority of pelvic floor symptoms arise—is an unexplored question. Medically, it is important to emphasize that pregnancy itself may for some women be enough to cause pelvic floor injury with the route of delivery playing only a minor role. Nonetheless, cesarean birth clearly appears to reduce the likelihood of multiple pelvic floor disorders. Pelvic nerve and muscle functions are generally protected by cesarean delivery (128), the timing of intervention largely determining the degree of protection. When cesareans were performed before the onset of their first labor, pudendal nerve injury is effectively prevented (139). Yet the same study found that cesareans performed after the onset of labor resulted in rates of nerve injury similar to vagin*l birth. The most protective cesareans appear to be those performed before the onset of a woman’s first labor.

Obstetric Issues and the Female Pelvis


Stress urinary incontinence is less common after cesarean compared with vagin*l birth, though it is not fully eliminated (117,140,141). After a first vagin*l delivery, the risk of incontinence is increased up to 2.8 times compared with cesarean section (117). Among women with a history of multiple gestation, delivery by cesarean-only confers a 50% reduction in the risk of stress urinary incontinence after controlling for age, parity, and body mass index (133). A randomized trial of vagin*l versus cesarean delivery, for breech presentation, revealed a significantly lower rate of urinary incontinence at 3 months postpartum in the cesarean group (142). Anal sphincter lacerations can follow cesarean deliveries performed late in labor (143) but are nearly nonexistent after cesareans that are performed before the onset of labor. And yet since anal incontinence is a relatively uncommon outcome, it remains uncertain under which circ*mstances an elective cesarean delivery would be an appropriate consideration for preventing anal injury. As mentioned, certain fetal position including “occiput posterior” may represent another potential high-risk group, since the risk for anal and perineal trauma is significantly increased (135). The broader application of “elective cesarean at term,” in the absence of specific risk factors, is a topic fraught with controversy. Even if the likelihood of postreproductive pelvic floor dysfunction could be decreased for some women, it would be essential to factor the broad medical impact and costs that would be required to achieve this narrow gain. Cesarean is by no means always in the best interest of mother or baby. Therefore, despite the fact that up to 31% of British female obstetricians would consider a cesarean delivery for themselves in order to prevent pelvic floor injury, most societies remain appropriately ambivalent regarding each woman’s “right to choose” cesarean birth. The full scope of issues regarding elective cesarean delivery is well beyond the scope of this chapter, but will undoubtedly gain increasing attention.



Despite the remarkable level of stress endured by the pelvic floor during labor and delivery, little attention is devoted to its recuperation afterward. Immediately postpartum, strategies for pelvic floor recuperation should be reviewed. Perineal care may include ice packs and lower-extremity elevation to counteract swelling. Proper perineal hygiene is also important to avoid infection and early suture breakdown. Lotions, ointments, and direct scrubbing of the perineal area should be avoided. Breastfeeding may contribute to pelvic floor symptoms during the postpartum period, as hypoestrogenic changes throughout the vagin* and lower urinary tract result in diminished urethral function, and occasionally increased severity of stress and urge incontinence. Estrogendependent symptoms will improve after the cessation of breastfeeding, as normal ovarian function resumes. Rehabilitation for the deeper pelvic floor should include pelvic floor exercises, resumed during the immediate postpartum period. An appropriate postpartum Kegel exercise routine may consist of two to five daily sessions of 10– 20 slow levator contractions for up to 10 sec. Exercising in the recumbent position may help to minimize caudal traction on the pelvic floor supports before full involution of the uterine fundus. Strengthening the perineal and levator musculature will help to improve vagin*l tone and restore the ability to “brace” the pelvic floor muscles during increased intra-abdominal pressure, a reflex that can be otherwise lost after childbirth. Several studies have demonstrated the potential efficacy of postpartum pelvic floor exercises in preventing incontinence and other pelvic floor symptoms (144). One study of 268 women, 3 months after their first delivery, demonstrated reduction in the rate of stress incontinence from 33% to 19% (145). Morkved and Bo demonstrated that postpartum urinary


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incontinence could be reduced by 8 weeks of structured group training combined with home exercises three time weekly, and that benefits are still present at 1 year postpartum (146,147). Supervised pelvic floor rehabilitation was also evaluated in a New Zealand study (148), randomly assigning women with postpartum urinary incontinence to either “intensive” pelvic exercises with personal instruction and multiple daily workouts, or “simple instruction.” At 1 year, the intensive group had less urinary incontinence, fecal incontinence, anxiety, and depression. However, their improvement remained for only as long as the exercises were continued. Trials randomizing women to either a structured pelvic floor exercise program or routine postpartum care have demonstrated modest reductions in the rate of stress incontinence with the structured treatment (149,150). When pelvic floor exercises are combined with with biofeedback and electrostimulation, one study demonstrated a reduction in stress incontinence for 19% of women, significantly .2% in the placebo group ( p ¼ .002) (151). Proper bowel and bladder habits should be emphasized after childbirth. After episiotomy or spontaneous perineal laceration, constipation and straining should be avoided to protect suture integrity, and to minimize stress against the pelvic floor muscles. For multiparas with descent of the perineal body, perineal branches of the pudendal nerve may be particularly prone to cumulative stretch injury during straining efforts. Pudendal nerve terminal motor latencies and descent of the perineum on straining are significantly associated in patients with fecal incontinence (152); the cause-effect of this relationship is not fully understood. Dietary fiber and stool softeners, along with occasional laxatives or suppositories, should be used as needed. Finally, returning to exercise and physical activity after childbirth should take into consideration the vulnerability of pelvic floor supports, with limited weight bearing to reduce abdominopelvic straining. “Bracing” the pelvic floor during sudden physical stress may be useful for reducing leakage episode and safeguarding the pelvic floor supports.



After childbirth has resulted in pelvic floor dysfunction, appropriate guidelines for managing the next pregnancy and delivery are often unclear. Perineal injuries represent one concern; although they are most common during a woman’s first vagin*l birth, “repeat” injuries can occur during subsequent deliveries. Women with a history of severe perineal laceration during their first delivery are up to 3.4 times likely to suffer a repeat injury in their next delivery (153). The same study indicated the highest risk among women undergoing forceps, vacuum, or repeat episiotomy in their second delivery—around one in five in this group—suffered a second severe perineal injury. Perineal massage during pregnancy and labor, attention to fetal size and position, and avoiding episiotomy and operative delivery whenever possible, appear to be the most effective strategies whether it is a woman’s first childbirth or a subsequent one (154). For pelvic prolapse following childbirth, there is no evidence suggesting that operative intervention should be routinely considered. Pudendal nerve injury can accumulation with later deliveries and presumably “set the stage” for the progression of prolapse, but it is unclear whether specific obstetrical interventions can help to counteract the progression of these changes. Patients should focus on symptom relief, consider the use of a pessary, and avoid strenuous activity until later in pregnancy. By 18 – 20 weeks, as the gravid uterus rises above the pelvic brim, prolapse symptoms will often improve for the remainder of pregnancy. Likewise, there is no clear evidence to support the use of elective cesarean section for parous women already affected by urinary incontinence. After previous stress incontinence surgery, elective cesarean for subsequent deliveries has been suggested to reduce the risk of recurrence (155), but

Obstetric Issues and the Female Pelvis


controlled trials are lacking. The risks and benefits need to be strongly considered for each individual. The management of childbirth after anal sphincter injuries represents another area of debate. Ultrasonography demonstrates that occult anal sphincter injuries can occur during second deliveries (156) and that the risk of anal incontinence increases, particularly among women with a sphincter defect diagnosed after the first delivery (157). Thus, although the first childbirth appears to be most important, postobstetrical pelvic floor injury can accumulate, with subsequent deliveries potentially causing new symptoms to arise, old ones to recur, or existing ones to worsen. A 1999 study (158) observed a cohort of Irish women experiencing some degree of fecal incontinence after their first vagin*l birth. Nearly all of those who remained symptomatic at the time of their next pregnancy noticed that symptoms became more severe following that next second pregnancy, the second birth still led to recurrence 40% of the time. Pudendal nerve latency was significantly longer after second delivery in this cohort, a finding corroborated by other studies (159). Strategies for preventing repeat injury vary widely, with some experts suggesting that event women with postpartum anal incontinence should be offered cesarean delivery since a loss of bowel control is arguably one of childbirth’s most distressing repercussions. According to survey data, up to 71% of colorectal surgeons would advise women with previous anal injuries to deliver by cesarean, versus only 22% of obstetricians. Because a broad strategy of cesarean delivery is not feasible, the identification of risk factors for injury is important. For instance, in the setting of macrosomia diagnosed by prenatal ultrasound, elective cesarean delivery may represent a sound strategy both medically and economically for the prevention of anal incontinence. The use of episiotomy in the setting of a previously repaired anal sphincter is another area of debate—recommended by only 1% of colorectal surgeons, compared with up to 30% of obstetricians. Future research will hopefully result in a broader consensus regarding the best preventive obstetrical approach.



Pelvic floor dysfunction among postreproductive women has emerged as a major area of interest in the realm of clinical practice and research. Our awareness of the numerous underlying pathophysiologic mechanisms continues to increase, including neuropathic change and anatomic alterations to muscular and connective tissue anatomy. A variety of procedures and events during labor and delivery, including episiotomy and operative delivery, may have implications for pelvic function afterward. These and other obstetrical practices should be weighed against their potential long-term effects on the maternal pelvic floor. As future research further clarifies the most significant determinants of obstetrical pelvic floor injury, efforts at prevention will undoubtedly improve.


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Johanson RB, Menon BK. Vacuum extraction versus forceps for assisted vagin*l delivery. Cochrane Database Syst Rev 2000; (2):CD000224. Jander C, Lyrenas S. Third and fourth degree perineal tears. Predictor factors in a referral hospital. Acta Obstet Gynaecol Scand 2001; 80(3):229– 234. Handa VL, Danielsen BH, Gilbert WM. Obstetric anal sphincter lacerations. Obstet Gynecol 2001; 98(2):225– 230. Riskin-Mashiah S, O’Brian Smith E, Wilkins IA. Risk factors for severe perineal tear: can we do better? Am J Perinatol 2002; 19(5):225– 234. Snooks SJ, Swash M, Henry MM, Sretchell M. Risk factors in childbirth causing damage to the pelvic floor innervation. Int J Colorectal Dis 1986; 1:20 –24. Meyer S, Schreyer A, De Grandi P, Hohlfeld P. The effects of birth on urinary continence mechanisms and other pelvic-floor characteristics. Obstet Gynecol 1998; 92(4 Pt 1):613– 618. Groutz A, Gordon D, Keidar R, Lessing JB, Wolman I, David MP, Chen B. Stress urinary incontinence: prevalence among nulliparous compared with primiparous and grand multiparous premenopausal women. Neurourol Urodyn 1999; 18(5):419– 425. Robinson JN, Norwitz ER, Cohen AP, Lieberman E. Predictors of episiotomy use at first spontaneous vagin*l delivery. Obstet Gynecol 2000; 96(2):214– 218. Bodner K, Bodner-Adler B, Wagenbichler P, Kaider A, Leodolter S, Husslein P, Mayerhofer K. Perineal lacerations during spontaneous vagin*l delivery. Wien Klin Wochenschr 2001; 113(19):743– 746. Goldberg RP, Kwon C, Gandhi S, Atkuru LV, Sorensen M, Sand PK. Urinary incontinence among ‘mothers of multiples’: the protective effect of cesarean delivery. Fitzpatrick M, McQuillan K, O’Herlihy C. Influence of persistent occiput posterior position on delivery outcome. Obstet Gynecol 2001; 98(6):1027– 1031. Pearl ML, Roberts JM, Laros RK, Hurd WW. vagin*l delivery from the persistent occiput posterior position. Influence on maternal and neonatal morbidity. J Reprod Med 1993; 38(12):955– 961. Robinson JN, Norwitz ER, Cohen AP, McElrath TF, Lieberman ES. Epidural analgesia and third- or fourth-degree lacerations in nulliparas. Obstet Gynecol 1999; 94(2):259– 262. Walker MP, Farine D, Rolbin SH, Ritchie JW. Epidural anesthesia, episiotomy, and obstetric laceration. Obstet Gynecol 1991; 77(5):668– 671. Al-Mufti R, McCarthy A, Fisk NM. Obstetricians personal choice and mode of delivery. Lancet 1996; 347– 544. Sultan AH, Kamm MA, Hudson CN. Pudendal nerve damage during labour: prospective study before and after childbirth. Br J Obstet Gynaecol 1994; 101(1):22– 28. Viktrup L, Lose G, Rolff M, Barfoed K. The symptom of stress incontinence caused by pregnancy or delivery in primiparas. Obstet Gynecol 1992; 79:945– 949. Faundes A, Guarisi T, Pinto-Neto AM. The risk of urinary incontinence of parous women who delivered only by cesarean section. Int J Gynaecol Obstet 2001; 72(1):41 –46. Hannah ME, Hannah WJ, Hodnett ED, Chalmers B, Kung R, Willan A, Amankwah K, Cheng M, Helewa M, Hewson S, Saigal S, Whyte H, Gafni A, Term Breech Trial 3-Month Follow-up Collaborative Group. Outcomes at 3 months after planned cesarean vs planned vagin*l delivery for breech presentation at term: the international randomized Term Breech Trial. JAMA 2002; 287(14):1822– 1831. Fynes M, Donnelly VS, O’Connell PR, O’Herlihy C. Cesarean delivery and anal sphincter injury. Obstet Gynecol 1998; 92(4 Pt 1):496– 500. Meyer S, Hohlfeld P, Achtari C, De Grandi P. Pelvic floor education after vagin*l delivery. Obstet Gynecol 2001; 97(5 Pt 1):673– 677. Reilly ET, Freeman RM, Waterfield MR, Waterfield AE, Steggles P, Pedlar F. Prevention of postpartum stress incontinence in primigravidae with increased bladder neck mobility: a randomised controlled trial of antenatal pelvic floor exercises. Br J Obstet Gynaecol 2002; 109(1):68– 76. Morkved S, Bo K. The effect of post-natal exercises to strengthen the pelvic floor muscles. Acta Obstet Gynaecol Scand 1996; 75(4):382– 385.

118 147. 148. 149. 150. 151. 152. 153. 154. 155. 156.

157. 158. 159.

Goldberg and Sand Morkved S, Bo K. Effect of postpartum pelvic floor muscle training in prevention and treatment of urinary incontinence: a one-year follow up. Br J Obstet Gynaecol 2000; 107(8):1022– 1028. Wilson PD, Herbison GP. A randomized controlled trial of pelvic floor muscle exercises to treat postnatal urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1998; 9(5):257 – 264. Chiarelli P, co*ckburn J. Promoting urinary continence in women after delivery: randomised controlled trial. BMJ 2002; 324(7348):1227 – 1228. Morkved S, Bo K. The effect of post-natal exercises to strengthen the pelvic floor muscles. Acta Obstet Gynaecol Scand 1996; 75(4):382– 385. Meyer S, Hohlfeld P, Achtari C, De Grandi P. Pelvic floor education after vagin*l delivery. Obstet Gynecol 2001; 97:673 – 677. Laurberg S, Swash M, Snooks SJ, Henry MM. Neurologic cause of idiopathic incontinence. Arch Neurol 1988; 45(11):1250– 1253. Payne TN, Carey JC, Rayburn WF. Prior third- or fourth-degree perineal tears and recurrence risks. Int J Gynaecol Obstet 1999; 64(1):55 – 57. Peleg D, Kennedy CM, Merrill D, Zlatnik FJ. Risk of repetition of a severe perineal laceration. Obstet Gynecol 1999; 93(6):1021– 1024. Casper FW, Linn JF, Black P. Obstetrical management following incontinence surgery. J Obstet Gynaecol Res 1999; 25(1):51 – 53. Abramowitz L, Sobhani I, Ganansia R, Vuagnat A, Benifla JL, Darai E, Madelenat P, Mignon M. Are sphincter defects the cause of anal incontinence after vagin*l delivery? Results of a prospective study. Dis Colon Rectum 2000; 43(5):590– 596. Faltin DL, Sangalli MR, Roche B, Floris L, Boulvain M, Weil A. Does a second delivery increase the risk of anal incontinence? Br J Obstet Gynaecol 2001; 108(7):684– 688. Fynes M, Donnelly V, Behan M, O’Connell PR, O’Herlihy C. Effect of second vagin*l delivery on anorectal physiology and faecal continence: a prospective study. Lancet 1999; 354(9183):983– 986. Tetzschner T, Sorensen M, Jonsson L, Lose G, Christiansen J. Delivery and pudendal nerve function. Acta Obstet Gynaecol Scand 1997; 76(4):324– 331.

8 History and Physical Examination in Pelvic Floor Disorders Sanjay Gandhi and Peter K. Sand Northwestern University, Evanston, Illinois, U.S.A.



Women with a pelvic floor disorder may present with a symptom, a previously identified physical sign, or a previously identified diagnosis. A clinician must take each of these and start a comprehensive inquiry into the patient’s medical history and constellation of symptoms. Further evaluation includes a focused general examination and a comprehensive genitourinary examination. Most evaluations will focus on pelvic organ prolapse and on urinary and fecal incontinence, but clinicians specializing in pelvic floor medicine will see a diverse range of problems. Knowledge of urology, gynecology, gastroenterology, and neurology is crucial in conducting an appropriate evaluation. A consistent methodology to evaluate patients with urogenital tract symptoms is most important in establishing the underlying etiology of the patient’s pelvic floor disorder. Effective treatment of pelvic floor disorders depends on an accurate diagnosis and an understanding of the patient’s expectations of treatment. The history, physical examination, and simple office testing may establish a preliminary diagnosis on which a clinician may begin treatment or may serve as an excellent screening tool to determine which individuals require further evaluation. If a complex or recurrent problem is present, surgery is planned, or the patient’s symptoms do not improve with initial treatment, specialized tests such as complex urodynamics should be employed to definitively establish diagnoses. Urogenital, gastrointestinal, musculoskeletal, neurologic, and endocrinologic factors may affect pelvic floor disorders, and a comprehensive history and physical examination begins the process of evaluating these conditions. Other, more specific criteria to select patients for further evaluation of urinary incontinence are listed in Table 1.



The history is an essential part of the evaluation of every female with a pelvic floor disorder. No urogenital tract symptom is pathognomonic for an underlying condition. While the history is limited in its specificity and is only the first step of the diagnostic inquiry into the patient’s disorder, it defines the problem by identifying the symptoms that must be explained by the 119


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Table 1 Criteria for Further Testing 1. Uncertain diagnosis and inability to develop a reasonable treatment plan based on the basic evaluation. Uncertainty in diagnosis may occur when there is lack of correlation between symptoms and clinical findings 2. Failure to respond to the patient’s satisfaction to an adequate therapeutic trial, and the patient is interested in pursuing further therapy 3. Surgical intervention planned 4. Hematuria without infection 5. Presence of any of the following conditions: Recurrent symptomatic UTI Persistent symptoms of difficult bladder emptying History of prior incontinence operation or radical pelvic surgery Significant genital prolapse Retention Neurological condition (e.g., multiple sclerosis or spinal cord lesions/injury) Source: Ref. 54.

evaluation. The clinician must evaluate information gathered from the patient history to selectively choose which diagnostic tests will reveal a condition’s etiology. A concise history may be obtained using premailed questionnaires providing the patient time to consider her symptoms, past medical history, and family history and reconfirm them. Bowel and bladder diaries or other chronological records of symptoms recorded at home may provide further clarification of the patient’s symptoms. An office interview supplements this initial history and should include an assessment of symptoms, risk factors for disease, and a general medical and social history. Most authors have found a medical history to be inadequate in establishing an accurate etiology of incontinence (1 – 6), with only a few exceptions. Farrar et al. concluded that history alone was accurate in establishing a diagnosis. Two of 56 women (3.6%) with stress incontinence symptoms alone and 89% of the 110 women with symptoms of urge incontinence were found to have detrusor overactivity on cystometry (7). Hastie and Moisey (8) also concluded that a history of pure stress incontinence was 100% accurate in establishing the diagnosis of genuine stress incontinence. In contrast, Jensen and colleagues (9) in a metaanalysis of thousands of patients found that reliance on history alone to identify genuine stress incontinence resulted in a misdiagnosis in 25% of patients. Patient history was an even less accurate predictor of detrusor overactivity, with a misdiagnosis in 45% of patients with a history of urge loss (9). In addition, advanced pelvic prolapse may mask underlying incontinence unless the pelvic prolapse is reduced (10 – 12). Ghoneim and colleagues (12) found in a small cohort of women that reducing the prolapse by a vagin*l pack during urodynamic testing demonstrated stress incontinence in 69% of women who were otherwise asymptomatic. Based on these studies, a clinician cannot depend on a patient’s symptoms to accurately reflect the underlying disorder. While the patient’s history will not be diagnostic, a complete assessment of symptoms will serve as an outline to guide the clinician’s evaluation.



Symptoms are the subjective indicator of disease or change in condition as perceived by the patient, her caregiver, or partner and may lead her to seek help from health care professionals (13). They are categorized separately from signs, conditions, and urodynamic observations (13).

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Anatomic, physiologic, and pathologic factors within the lower urogenital tract as well as nongenitourinary factors or conditions may result in pelvic floor disorders with a variety of acute or chronic symptoms. Recurrent symptoms may represent acute exacerbations of chronic disease. Women seeking care of a pelvic floor medicine specialist may present with symptoms of disease in the lower or upper urinary tract, in the gynecologic or gastrointestinal organs, or in the musculoskeletal or neurological system. Therefore, only a comprehensive review of systems will assure the clinician that all aspects of the disease process are being assessed. A.

Systemic Manifestations

Systemic manifestations of urogenital tract disorders include fever and weight loss. While simple acute cystitis typically does not cause a fever, acute pyelonephritis in adults typically causes high fevers with rigors and costovertebral angle tenderness. In children, simply the presence of fever should prompt the clinician to perform a bacteriologic evaluation of the urine, as often no other localizing signs or symptoms of a renal infection may be present. Renal infection may also present differently with recurrent fevers in the absence of other urinary tract symptoms or with no fevers at all. Chronic pyelonephritis may only present with general malaise. While infection is the typical cause of fevers, renal cell carcinoma may present with fevers. Weight loss and general malaise are nonspecific symptoms that may prompt one to consider urogenital tract pathology such as advanced stages of cancer or renal insufficiency due obstruction or infection. B.


The most common symptom of pelvic floor dysfunction is urinary incontinence—the involuntary leakage of urine. Urinary incontinence should be described by type, frequency, severity, precipitating factors, and impact on hygiene and on a patient’s social activities. The clinician should understand the measures a patient uses to contain the leakage. Finally, it is crucial for the clinician to assess the impact of the incontinence on a patient’s quality of life and on her caregivers. Understanding a partner, caregiver, or patient’s expectations of treatment is crucial to rendering effective care. The original ICS definition of incontinence—“Urinary incontinence is the involuntary loss of urine that is a social or hygienic problem”—relates the complaint of incontinence to quality of life issues. Whether or not the individual or their caregiver seeks or desires help because of urinary incontinence should be known prior to beginning an evaluation. 1.

Stress Urinary Incontinence

The symptom of stress urinary incontinence is the involuntary loss of urine during coughing, sneezing, laughing, or other physical activities that increase intra-abdominal pressure. Stress incontinence, the sign, is the observation of involuntary leakage from the urethra with exertion, coughing, or sneezing. Urodynamic stress incontinence, the condition, is defined as the involuntary loss of urine during an increase in intra-abdominal pressure in the absence of a detrusor contraction. This occurs when the bladder pressure exceeds the urethral pressure because of decreased transmission of intra-abdominal pressure to the urethra. This is usually secondary to urethral hypermobility. The decrease in transmission of intra-abdominal pressure to the urethra relative to the bladder is referred to as a deficient extrinsic continence mechanism. Incontinence can also occur secondary to deficient intrinsic urethral sphincteric function. The smooth muscle, skeletal muscle, periurethral vasculature, and intrinsic urethral fibrous


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tissue all contribute to the resting urethral resistance or tone. Intrinsic sphincteric deficiency is the condition where the urethral sphincter is unable to generate enough resistance to retain urine in the bladder. Intrinsic urethral function can be measured urodynamically by calculating the resting urethral closure pressure. The leak point pressure is also used by some investigators to measure both the extrinsic and intrinsic continence mechanisms. Although increased age and multiparity are thought to increase the risk of stress incontinence, we know that even in nulliparous women with a well-supported urethra and an intact sphincter (normal urethral pressures), urinary incontinence may be present in as many as 50% of women (14,15). In elite female athletes, urinary loss may be present in up to 52% during their sport (16,17). 2. Urge Urinary Incontinence The symptom of urge urinary incontinence is the involuntary loss of urine accompanied by or immediately preceded by a sudden compelling desire to pass urine, which is difficult to deter (i.e., urgency). Women with urge incontinence often demonstrate, on urodynamics, involuntary detrusor contractions, or detrusor overactivity. The prevalence of detrusor overactivity appears to increase with age. 3.

Mixed Urinary Incontinence

Women with symptoms of both urge and stress urinary incontinence are said to have mixed urinary incontinence. Often one symptom is more bothersome than the other, and the clinician should attempt to make this differentiation. C.


A patient may feel local pain near the involved organ. Acute pyelonephritis manifests with pain in the costovertebral angle and the flank. In contrast, the spatial displacement of pain sensation from the point of stimulation is known as referred pain. Convergence of many sensory inputs to a single pain transmission neuron in the spinal cord underlies the phenomenon of referred pain. The brain has no way of knowing the source of the pain and mistakenly projects the pain sensation to a site distant from the original point of stimulation in the diseased organ (18). Ureteral colic is a classic symptom with referred pain. In women, ureteral calculi may result in pain felt in the vulva or inner thigh. Inflammation of the bladder trigone as seen in acute cystitis often results in terminal dysuria felt at the urethral meatus. 1.

Renal Pain

Renal pain or colic is typically felt in the area lateral to the sacrospinalis muscle and below the 12th rib. This pain may spread along the subcostal area around to the umbilicus or lower abdomen (19). Such pain is typical in conditions that cause acute distension of the renal capsule such as acute pyelonephritis or acute ureteral obstruction from urolithiasis. Many conditions, however, are painless as they progress slowly without capsular distension including neoplasia, chronic pyelonephritis, staghorn calculi, polycystic kidney disease, and hydronephrosis from chronic ureteral obstruction (as seen in cervical cancer, massive fibroid tumors, or severe pelvic organ prolapse). 2.

Pseudorenal Pain (Radiculitis)

Musculoskeletal derangements of the thoracic spine may irritate costal nerves, causing pain that mimics renal pain. Lifting of a heavy object, trauma to the flank, or a sudden fall may precipitate

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such pain. Relief of this pain by changes in position and movement of the spine differentiates it from true renal colic (19). 3. Ureteral Pain Acute obstruction by calculi or blood clots typically results in ureteral pain. Renal capsular distension causes back pain, and ureteral muscle spasm elicits severe colicky pain from the costovertebral angle down toward the lower anterior abdominal quadrant along the course of the ureter. Stones in the midportion of the ureter on the right side may simulate appendicitis with referred pain to McBurney’s point, while on the left, ureteral pain may resemble diverticulitis. A stone at the ureteral orifice may cause inflammation and edema in the bladder, producing lower urinary symptoms such as urgency and frequency. Finally, if the calculus is small, it may not even cause pain. 4. Vesical Pain Overdistension of the bladder from acute retention causes severe suprapubic or retropubic pain. Chronic retention from bladder outlet obstruction or an acontractile bladder typically does not result in significant vesical pain even though the bladder may reach the level of the umbilicus. Interstitial cystitis or bladder ulceration caused by tuberculosis or schistosomiasis infection may cause suprapubic pain or discomfort when the bladder fills even to small volumes. Because these conditions often result in diminished bladder capacities, voiding results in significant relief of their suprapubic discomfort. Associated symptoms include urgency and frequency. Detrusor overactivity, which also causes urgency and frequency, does not commonly cause bladder pain. As stated earlier, bladder infection often results in referred pain to the distal urethra. D.

Abdominal and Gastrointestinal Symptoms of Urogynecolgic Disease

Gastrointestinal symptoms often accompany renal and ureteral disease. The gastrointestinal and genitourinary systems share common autonomic and sensory innervations. Afferent stimuli from the renal capsule may, by reflex, alter the tone of smooth muscle in the enteric tract leading to gastrointestinal manifestations of renal disease. Enlargement of the kidneys may abut or displace intraperitoneal organs (e.g., stomach, colon, liver, gallbladder), causing gastrointestinal symptoms while inflammation may result in peritoneal irritation that results in muscle rigidity and rebound tenderness on abdominal examination. Abdominal pain, distension, nausea, and vomiting secondary to renointestinal reflexes are all common accompanying symptoms of acute pyelonephritis and ureteral colic. The connection between severe pelvic organ prolapse and abdominopelvic symptoms is less clear. Although anecdotally a large enterocele may lead to peritoneal irritation that may produce abdominal pain and gastrointestinal distress, Heit and Culligan (20) recently reported that pelvic organ prolapse was not associated with pelvic pain when controlling for patient age and prior prolapse surgery. E.

Dyspareunia and Vulvodynia

Dyspareunia is pain in the pelvic area during or after intercourse. It occurs with vagin*l penetration—either at the introitus or deep in the vagin*. Differentiation between locations of pain with intercourse may point to distinct etiologies. Pain with deep penetration may suggest endometriosis, vagin*l infection, or interstitial cystitis, while pain with initial intromission is more suggestive of vestibulitis, urethrotrigonitis, or vulvodynia.


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Vulvodynia is chronic vulvar pain. It may be present constantly, intermittently, or only with intromission during intercourse. Activities that cause friction or pressure on the vulva aggravate the allodynic symptoms. Wearing tight pantyhose or jeans may elicit vulvar pain. Urine-soaked pads, excessive perspiration, and allergens may cause inflammation of the small vestibular glands and epithelium (i.e., vestibulitis) with secondary vulvodynia.


Medical and Social History

There are many medical conditions that may cause or aggravate urinary incontinence. The clinician should exclude these when evaluating a woman with urinary incontinence. One should take a medical, neurological, and genitourinary history including a detailed exploration of symptoms. The medications and supplements used by the patient should be carefully reviewed. The history should also include information on previous surgery, trauma, radiation therapy, use of hormone replacement, past medical history, and current active medical conditions. Information on previous urogynecologic treatments and assessment of their impact on current symptoms may be helpful. Other associated pelvic floor dysfunction involving bowel or sexual function is important to identify as these conditions may be interrelated with the patient’s lower urinary tract symptomatology and may have been previously unrecognized. Correction of some reversible causes of urinary incontinence may resolve or improve their incontinence (Table 2) (21). Medications can often impact urinary symptoms such as incontinence or retention (Table 3). Assessment should include psychosocial and environmental questions. An understanding of how a patient’s problem impacts her daily living is crucial to providing appropriate and timely treatment. While pelvic prolapse may directly cause pain or discomfort and thus impact wellbeing, incontinence has broad psychological effects that may prevent an otherwise functional or healthy woman from leaving her home. An understanding of a patient’s environmental conditions at home may help identify individuals with incontinence who are at risk for falls or fractures (22). Urinary symptoms can often force the elderly to hastily move to the toilet in less than ideal circ*mstances. A questionnaire can serve as a screening tool for psychosocial and environmental conditions that impact the patient’s quality of life. Knowledge of the amount and types of pads, briefs, and protective devices may provide insight into the extent of debilitation caused by a patient’s incontinence. In elderly individuals, a mental status evaluation and assessment of physical mobility is important. An understanding of a patient’s access to toilets, especially at night, when the elderly may be at greater risk of falls and

Table 2 Reversible Causes of Incontinence DIAPPERS Delirium or confusion Infection, urinary tract Atrophic genital tract changes (vaginitis or urethritis) Pharmaceutical agents (see Table 3). Psychologic Excess urine production (excess fluid intake, volume overload, metabolic such as hyperglycemia or hypercalcemia) Restricted mobility (chronic illness, injury, or restraint) Stool impaction

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Table 3 Drugs That May Affect Lower Urinary Tract

Class of drugs Psychotropic agents Antidepressants Antipsychotics Sedatives/hypnotics Alcohol Caffeine Diuretics Narcotics ACE inhibitors

Side effect Anticholinergic, sedation Anticholinergic, sedation Sedation, muscle relaxation, confusion Sedation, impaired mobility

Sedation, delirium Cough

Calcium-channel blockers Anticholinergic Alpha-adrenergic agonists Alpha-adrenergic blockers Beta-adrenergic agonists

Increased urethral tone Decreased urethral tone Inhibited detrusor function

Impact on lower urinary tract function Urinary retention Urinary retention Urinary retention Diuresis, frequency Urgency, frequency Polyuria, urgency, frequency Urinary retention, fecal impaction Aggravate preexisting stress incontinence Urinary retention, overflow incontinence Urinary retention, overflow incontinence Urinary retention Stress incontinence Urinary retention

injuries, of their living arrangements, and of the involvement of caregivers will help the clinician plan an individualized treatment plan. Signs of lower urinary tract dysfunction are observed by the physician to verify symptoms and quantify them. Observations from bladder diaries, pad tests, and validated questionnaires are examples of other instruments used to confirm and quantify symptoms.



Filling out a standardized questionnaire at home before coming into the office may help patients clarify and enhance their understanding of their symptoms. This gives patients time to delineate their symptoms, increase the accuracy of their answers, and obtain information from other family members if needed. It also speeds up their office evaluation. Various validated questionnaires are useful not only to quantify the severity of symptoms and their impact on quality of life, but to provide quantitative data for use in research studies and outcomes analysis. Generalized health-related quality-of-life (HRQOL) instruments enable researchers to compare groups with different diseases. However, condition-specific instruments best allow the clinician to assess the impact of urogenital symptoms on a particular woman. Table 4 presents a list of some of the numerous validated questionnaires that have been developed for collecting and reporting subjective information about pelvic floor disorders in women. Unfortunately, no single instrument has emerged as the preferred one since questionnaires vary widely, depending on their intended purpose and target population (23). Choosing the appropriate questionnaire—one that is comprehensive yet easy for patient to complete—may be challenging. These questionnaires may be modified to meet the needs of a specific clinician or practice and may be included in a general information packet.


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Table 4 Validated Questionnaires Generalized Condition-specific Urinary incontinence

Sexual dysfunction Pelvic organ prolapse Defecatory dysfunction Interstitial cystitis


Medical Outcomes Survey Short Form-36 (SF-36) (55) Incontinence Impact Questionnaire (IIQ) (56) Urinary Distress Inventor (UDI) (56) IIQ-7 and UDI-6 (57) Incontinence Quality of Life Measure (I-QOL) (58) King’s Health Questionnaire (59) Bristol Female Lower Urinary Tract Symptom Questionnaire (60) York Incontinence Perception Scale (YIPS) (61) Medical Epidemiologic and Social Aspects of Aging (MESA) Urinary Incontinence Questionnaire (UIQ) Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ) (62), PISQ-12 Pelvic Floor Dysfunction Inventory (PFDI) (63) Fecal Incontinence Quality of Life Scale (64) Pelvic Floor Dysfunction Inventory (PFDI) (63) Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) (65)

Bladder Diary

Bladder diaries assist in providing quantitative data on urinary frequency, voiding intervals, the volume of continent voids, and the number of incontinent episodes. They also enable the clinician to better understand triggers of incontinence such as coughing, exercises, Valsalva, or strenuous activity. Bladder diaries (Fig. 1) help to accurately assess fluid intake patterns, including the consumption of caffeine-containing fluids. The diary may help to establish voiding patterns that can help clinicians select appropriate behavioral interventions, and may also serve as a baseline of symptom severity for assessment of treatment efficacy. Seven-day bladder diaries have been found to correlate well with actual symptoms and incontinence severity (24). In addition, while filling out a diary may be tedious, the process of filling out a diary may in itself be a form of bladder training, resulting in an improvement in incontinence symptoms. B.

Physical Examination

The physical examination attempts to identify neurological deficits, defects in pelvic support, pelvic pathology, infection, estrogen deficiency, tenderness, and other urogenital problems. One must employ a methodical approach to the evaluation of the urogenital tract for pathology. In addition, a systematic general physical and neurological examination may also reveal other causes (e.g., cardiac, endocrine) of urogynecologic symptoms. 1. Neurological Examination The screening neurological examination should include an evaluation of mental status, gait, and the lumbosacral nerves. A complete evaluation of the lumbosacral nerve roots includes testing of deep tendon reflexes, sensation (Fig. 2), and strength in the lower extremities as well as the bulbocavernosus and cl*toral sacral reflexes (Fig. 3). Isolated deficits are often not a cause of urogenital symptoms, and a comprehensive neurological examination may seem to be of low


Figure 1 Bladder Diary.

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Figure 2 Sensory dermatomes.

yield (Table 5). However, simple observations (e.g., deep tendon hyperreflexia, intention tremor, or the presence of altered mental status) may identify women with predisposing functional impairments (e.g., dementia, Parkinson’s disease, spinal cord disease, or previous strokes) that explain their urinary symptoms. Urinary retention and/or incontinence may be the first sign of multiple sclerosis in an otherwise healthy woman (25).

Figure 3 Examination of bulbocavernosus and cl*toral reflexes.

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Table 5 Significance of Abnormal Findings on Neurologic Testing Examination Sensory testing around knee (light touch, pin prick) Deep tendon reflexes Babinski Muscle strength: Flexion extension knees Flexion hips Extension hips Plantarflexion ankles Dorsiflexion ankles Gait Bulbocavernosus/anal wink

Neurological level L2-S2 and peripheral nerves Upper and lower motor neurons Corticospinal tracts

Significance of findings Mapping altered sensations to follow either dermatome or a peripheral nerve distribution determines level of injury Hyperreflexia—UMN lesion Absent—LMN lesion Fanning and dorsiflexion; interruption of tracts Neuropathy or simply muscular weakness

(L3-L5) (L4-L5) (L2-L3) (S1-S2) (L4-L5) Cerebellum L5-S5 and pudendal nerve

Cerebellar lesion: stroke or tumor Pudendal neuropathy or other sacral nerve injury (66)

Source: Ref. 34.

2. General Examination All women presenting for evaluation of pelvic floor dysfunction should undergo age-appropriate routine health checks and cancer screening according to the U.S. Preventive Services Task Force (26 – 28). Pulmonary and cardiovascular examination may identify individuals with chronic cough or those in need of diuretics for fluid overload. The back is examined for vertebral or flank tenderness or paraspinal muscle spasm. Masses, ascites, and organomegaly can influence intra-abdominal pressure and impact urinary tract function. Visual inspection of the abdomen will reveal any scars from surgeries unexplained by the patient’s history or unusual distention of the abdomen. In addition to palpating the abdomen to assess for hepatosplenomegaly, masses, distention, and tenderness, a Valsalva maneuver and cough will reveal any hernias. Palpation of the inguinal area may reveal lymphadenopathy. 3. Gynecologic Examination Inspection of the external genitalia will reveal any lesions or skin changes. “Rashes” may indicate chronic irritation from urine or feces. Whitish skin changes, erythema, or loss of normal architecture of the vulva may indicate hypoestrogenism or vulvar dystrophies. In women with introital dyspareunia or vulvodynia, a careful examination of the vagin* and vestibule to Hart’s line is important. Hart’s line is the mucocutaneous junction where the outer vestibule meets the squamous epithelium of the labia minora. A Q-tip and a pain scale may be used to elicit point tenderness in this area. Asking the patient to rate the pain on a scale of 0 to 5 will enable the clinician to identify the exact location of the pain and the point of maximal tenderness. Speculum examination should include an inspection of the cervix or vagin*l cuff and notations of any lesions, discharge, inflammation, or atrophy. Several gynecologic surgeons have attempted to develop classification systems to categorize pelvic organ prolapse over the years. Figure 4 provides a comparison of major

Figure 4

Comparison of pelvic organ classification systems.

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prolapse classification systems. In 1996, the American Urogynecologic Society and the Society of Gynecologic Surgeons adopted the International Continence Society’s Pelvic Organ Prolapse Quantification (POP-Q) system (29). The system has been demonstrated to be learned easily and performed quickly with highly reproducible findings between and within observers (30). However, the classification lacks sensitivity to detect anterior and posterior wall prolapse in the upper vagin*l vault and may confuse redundant suburethral vagin*l tissue or urethral hypermobility with significant cystoceles. In addition, women with pelvic organ prolapse experience symptoms that do not necessarily correlate with compartment-specific defects identified by the POP-Q classification system (31). While many research centers have adopted this system in favor of the Baden Half Way system, widespread use of the POP-Q system by all practitioners that perform pelvic examinations is hampered by its relative complexity. Although limitations of the POP-Q system exist, it is a sensitive measure of change in pelvic prolapse in an individual patient. A uniform system of describing prolapse is necessary to facilitate collaborative communications and research.



The POP-Q system of assessing pelvic support unlike other prolapse grading systems quantifies descent of the vagin*l wall rather than speculating on what is on the other side of the vagin*l epithelium. It avoids specific labels such as cystocele, rectocele, or enterocele recognizing, for example, that an anterior wall defect may not be the result of a cystocele. Table 6 and Figure 5 describe the different points used in the POP-Q system for describing prolapse, and Figure 6 shows the grid used to record the findings. Table 7 lists the stages of pelvic organ prolapse that

Table 6 POP-Q Points of Reference Point Points A Aa Ba Points B

Ba Bp C D GH (genital hiatus) PB (perineal body) TVL (total vagin*l length)

Definition 3 cm proximal to or above the hymen in the midline, values from 23 cm (no prolapse) to þ3 cm (maximal prolapse) Anterior, corresponds to location of the urethrovesical junction Posterior Lowest extent of the segment of the vagin* between point A and the apex of the vagin*, values from 3 cm to TVL location not fixed If point A protrudes the most (situation in most women without severe prolapse), then point B ¼ point A Anterior Posterior Most distal part of the cervix or in women after hysterectomy, the vagin*l cuff Posterior fornix Omitted after hysterectomy Distance (cm) from middle of the external urethral meatus to the posterior midline hymen Distance (cm) from the posterior midline hymen to the midanal opening Greatest depth of vagin* (cm) when prolapse is fully reduced Avoid excessive pressure or stretching


Gandhi and Sand

Figure 5 Reference points for POP-Q measurements.

are assigned based on the POP-Q examination when the full extent of the prolapse has been demonstrated. Performing a systematic pelvic examination enables the practitioner to consistently assess patients and follow their progress longitudinally. We separate the speculum and place the lower blade in posteriorly and hold a ruler or calibrated Q-tip 3 cm away from the urethral meatus. While pulling the speculum blade posteriorly, we ask the patient to perform a Valsalva maneuver and measure the descent of point Aa. At this time, the most dependent part of any anterior wall prolapse is also measured (Ba). By inspecting the vagin*l rugae of the anterior wall, one may gain a hint of whether lateral and or central defects have caused anterior vagin*l wall prolapse. If the vagin*l rugae appear to be prominent in the midline, it may be indicative of a paravagin*l defect. Direct assessment of the support of anterior lateral vagin*l sulcus is used as a more definitive marker of diagnosing a paravagin*l defect unilaterally or bilaterally. This may be

Pelvic Floor Disorders


Figure 6 Grid for recording prolapse measurements.

assessed during the speculum exam with the aid of ring forceps or a Baden defect analyzer elevating the anteriorlateral vagin*l sulcus to the level of the arcus tendineous and observing if normal anterior vagin*l wall support is restored. This may result in artifact and misdiagnosis if the opened instrument is elevated above the level of the arcus tendineus. In one study, while the sensitivity of the clinical assessment of paravagin*l defects in comparison with the operative confirmation of the defects was 92%, the specificity of 53% was poor (32). We prefer a simpler, more consistent alternative to performing this assessment that can avoid any potential over correction artifact. We take both halves of a Grave’s speculum and insert them bilaterally along the lateral vagin*l walls in the vertical axis. If the cystocele is resolved completely, it is probably secondary to a unilateral or bilateral paravagin*l defect. Removing each blade with the other in place will elucidate whether it is a bilateral or unilateral paravagin*l defect. If the anterior vagin*l wall descent is not completely corrected, it probably Table 7 Staging of Pelvic Organ Prolapse Based on the POP-Q Examination Stage


No descensus of pelvic structures during straining (Aa, Ap, Ba, Bp ¼ 23 and C or D 2([tvl 2 2])


The leading surface of the prolapse does not descend below 1 cm above the hymenal ring (i.e., prolapse is not stage 0 and all points are ,21)


The leading edge of the prolapse extends into the region from 1 cm proximal to the hymen to 1 cm distal to the hymen (i.e., most distal point is 21 but þ1)


The leading edge of the prolapse extends 1 cm beyond the hymen, but there is not complete vagin*l eversion (i.e., most distal point is .þ1 but ,þ[tvl22])


Essentially complete eversion (i.e., most distal point is þ[tvl22])


Gandhi and Sand

represents a combination of central and paravagin*l defects. This method is relatively quick and may avoid the common overdiagnosis of paravagin*l defects. By rotating the speculum blade 1808 and reinserting it along the anterior vagin*l wall, the clinician can inspect the posterior wall and uterine or vagin*l apex mobility. Digital examination will help to measure vagin*l length (TVL) as well as descent of the apex (C and/or D). Finally, external examination will give measurements of the genital hiatus (GH) and perineal body (PB). On bimanual examination, initial palpation of the posterior fourchette to assess for tenderness at the introitus and palpation of the posterior vagin*l wall and deeper pelvic musculature to assess for tenderness or spasm of the levator ani muscle may help to identify sources of dyspareunia. Palpation of the urethra and bladder neck may reveal tenderness or masses that should be further evaluated with urethroscopy and cystoscopy. Routine assessment of contour, size, and abnormalities of the pelvic organs is performed focusing on the presence of pelvic tenderness or masses. Rectovagin*l examination helps to assess the anal sphincter tone, possible sphincter defects, fecal impaction, the presence of occult blood or rectal lesions, and subtle distal rectoceles. Asking the patient to contract her levator ani muscles during this examination will help the clinician assess her ability to contract the muscles, the strength of the contraction, and the duration of the contraction. The pelvic muscles have been considered integral to continence since Kegel (33) observed that women with urinary incontinence experienced symptomatic improvement by improving the strength of these muscles. The pubococcygeous and puborectalis components of the levator ani form a hammock beneath the rectum and insert superiorly and laterally upon the pubic rami. Contraction of these muscles, especially during strenuous physical activity, compresses the rectum, vagin*, and urethra, maintaining flatal, fecal, and urinary continence (34). Although the utility of this assessment may be questioned, it is useful to grade levator strength to better implement behavioral interventions such as pelvic floor muscle exercises, biofeedback, or electrical stimulation. Many patients will have no ability to contract their levator ani. Pelvic floor exercises without “biofeedback” in those women would be futile. Various techniques to assess levator ani tone (35 – 42) have been studied, although no single technique is widely accepted. The modified Oxford scale is presented in Table 8 (39). Given the lack of a standardized scale, the clinician should adopt a single scale and consistently use it to preserve internal consistency. 4.

Measuring Urethral Hypermobility: Q-tip Test

If we believe that the underlying pathophysiology of most stress urinary incontinence (previously identified as genuine stress incontinence) involves urethral hypermobility, then some assessment of urethral mobility should be made. The Q-tip test is an excellent test to document quantitatively the presence of urethral hypermobility (43,44). It was originally designed to take the place of the bead chain cystourethrogram in the evaluation of the urethral

Table 8 Modified Oxford Scale for Measuring Pelvic Muscle Strength Number 0 1 2 3 4 5

Definition No palpable muscle contraction Flicker Weak pelvic contraction Moderate contraction with an element of lift Good contraction with lift and holding power Strong squeeze with good lift gripping examining hand

Pelvic Floor Disorders


axis. Although the determination of urethral hypermobility is a poor predictor of the etiology of a patient’s urinary incontinence (45 – 47), it has been included in the urogynecologic examination to assess urethrovesical junction support. To perform the test, a sterile cotton applicator soaked in 2% Xylocaine jelly is inserted into the urethra, and withdrawn slowly until slight resistance indicates that the tip is at the bladder neck. A goniometer or compass (Fig. 7) provides a measurement of the resting angle from the horizontal. The patient is then asked to repetitively cough and perform Valsalva maneuvers while the maximum straining angle is measured (Fig. 8). If the cotton tip is not in the bladder, the angle will be underestimated. A straining angle 308 has been arbitrarily suggested to indicate significant bladder neck mobility. Few normative data are available regarding these measurements and factors during testing that may affect measurements. Walters and Diaz (48) reported that asymptomatic women with a mean parity of two and mean age of 32 had an average maximum straining angle of 548. Although this was less than the straining angle of 738 seen in a group of symptomatic women, there was considerable overlap between groups (48). Fedorkow and colleagues (49) performed a receiver-operator characteristic analysis and found the optimal diagnostic cutoff point for stress urinary incontinence to be 408 from the horizontal. At this cutoff, 84% of patients with genuine stress incontinence would have a positive test. Thus, an arbitrary cutoff of 308 in parous women may be too low. Handa and colleagues (50) noted that 71% of women diagnosed with urethral hypermobility in the supine position did not have urethral hypermobility in the standing position. This observation brings into question the reproducibility of the Q-tip test. Despite this information, the test is still used by many in making decisions in selecting treatments for stress incontinence primarily because the absence of a positive Q-tip test in someone diagnosed with

Figure 7 Goniometer used for measuring Q-tip angle.


Gandhi and Sand

Figure 8 Demonstration of resting and straining angles during the Q-tip test.

stress incontinence is important. Bergman and colleagues (51), using a Q-tip test cut-off point of 358, found a 50% failure rate in women with stress incontinence and negative Q-tip tests who underwent Pereyra operations and a 55% failure rate for women who had Burch procedures. By asking the patient to cough at this time, one can perform a supine empty stress test as a screen for a low pressure urethra or a low leak point pressure (52,53). This simple test has been identified as a very specific and reasonably sensitive test to assess for intrinsic sphincteric deficiency. Finally, we repeat a vagin*l examination while the patient bears down in the standing position to reassess for the sign of stress incontinence and for increased genital prolapse with gravity. Occasionally, pelvic organ descent may only be evident with the help of gravity.



A careful history and physical examination will guide the clinician in further evaluation of the patient’s symptoms or allow them to begin empiric treatment in uncomplicated pelvic floor disorders.


Haylen BT, Sutherst JR, Frazer MI. Is the investigation of most stress incontinence really necessary? Br J Urol 1989; 64:147 – 149. Cundiff GW, Harris RL, Coates KW, Bump RC. Clinical predictors of urinary incontinence in women. Am J Obstet Gynecol 1997; 177:262 – 266; discussion 266– 267. Sand PK, Hill RC, Ostergard DR. Incontinence history as a predictor of detrusor stability. Obstet Gynecol 1988; 71:257 – 260.

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Cardozo LD, Stanton SL. Genuine stress incontinence and detrusor instability—a review of 200 patients. Br J Obstet Gynaecol 1980; 87:184 – 190. Glezerman M, Glasner M, Rikover M, Tauber E, Bar-Ziv J, Insler V. Evaluation of reliability of history in women complaining of urinary stress incontinence. Eur J Obstet Gynecol Reprod Biol 1986; 21:159 –164. Ouslander J, Staskin D, Raz S, Su HL, Hepps K. Clinical versus urodynamic diagnosis in an incontinent geriatric female population. J Urol 1987; 137:68 – 71. Farrar DJ, Whiteside CG, Osborne JL, Turner-Warwick RT. A urodynamic analysis of micturition symptoms in the female. Surg Gynecol Obstet 1975; 141:875 –881. Hastie KJ, Moisey CU. Are urodynamics necessary in female patients presenting with stress incontinence? Br J Urol 1989; 63:155– 156. Jensen JK, Nielsen FR Jr, Ostergard DR. The role of patient history in the diagnosis of urinary incontinence. Obstet Gynecol 1994; 83:904 – 910. Fianu S, Kjaeldgaard A, Larsson B. Preoperative screen for latent stress incontinence in women with cystocele. Neurourol Urodyn 1985; 4:3 – 7. Bergman A, Koonings PP, Ballard CA. Predicting postoperative urinary incontinence development in women undergoing operation for genitourinary prolapse. Am J Obstet Gynecol 1988; 158:1171– 1175. Ghoniem GM, Walters F, Lewis V. The value of the vagin*l pack test in large cystoceles. J Urol 1994; 152:931– 934. Abrams P, Cardozo L, Fall M. The standardisation of terminology of lower urinary tract function: report from the Standardisation Subcommittee of the International Continence Society. Am J Obstet Gynecol 2002; 187:116 – 126. Bo K, Stien R, Kulseng-Hanssen S, Kristofferson M. Clinical and urodynamic assessment of nulliparous young women with and without stress incontinence symptoms: a case-control study. Obstet Gynecol 1994; 84:1028 – 1032. Wolin LH. Stress incontinence in young, healthy nulliparous female subjects. J Urol 1969; 101:545– 549. Thyssen HH, Clevin L, Olesen S, Lose G. Urinary incontinence in elite female athletes and dancers. Int Urogynecol J Pelvic Floor Dysfunct 2002; 13:15 –17. Nygaard IE, Thompson FL, Svengalis SL, Albright JP. Urinary incontinence in elite nulliparous athletes. Obstet Gynecol 1994; 84:183 – 187. Fauci. Harrison’s Principles of Internal Medicine. McAninch J. Symptoms of Disorders of the Genitourinary Tract in General Urology. Heit M, Culligan P, Rosenquist C, Shott S. Is pelvic organ prolapse a cause of pelvic or low back pain? Obstet Gynecol 2002; 99:23– 28. Resnick NM, Yalla SV. Management of urinary incontinence in the elderly. N Engl J Med 1985; 313:800– 805. Brown JS, Vittinghoff E, Wyman JF. Urinary incontinence: does it increase risk for falls and fractures? Study of Osteoporotic Fractures Research Group. J Am Geriatr Soc 2000; 48:721 – 725. Graham CW, Dmochowski RR. Questionnaires for women with urinary symptoms. Neurourol Urodyn 2002; 21:473 –481. Wyman JF, Choi SC, Harkins SW, Wilson MS, Fantl JA. The urinary diary in evaluation of incontinent women: a test-retest analysis. Obstet Gynecol 1988; 71:812– 817. Beck RP, Warren KG, Whitman P. Urodynamic studies in female patients with multiple sclerosis. Am J Obstet Gynecol 1981; 139:273– 276. Calonge N. New USPSTF guidelines: integrating into clinical practice. US Preventive Services Task Force. Am J Prev Med 2001; 20:7 – 9. Berg AO, Allan JD. Introducing the third US Preventive Services Task Force. Am J Prev Med 2001; 20:3– 4. Franco EL, Duarte-Franco E, Rohan TE. Evidence-based policy recommendations on cancer screening and prevention. Cancer Detect Prev 2002; 26:350 – 361.

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Gandhi and Sand Bump RC, Mattiasson A, Bo K. The standardization of terminology of female pelvic organ prolapse and pelvic floor dysfunction. Am J Obstet Gynecol 1996; 175:10 – 17. Hall AF, Theofrastous JP, Cundiff GW. Interobserver and intraobserver reliability of the proposed International Continence Society, Society of Gynecologic Surgeons, and American Urogynecologic Society pelvic organ prolapse classification system. Am J Obstet Gynecol 1996; 175:1467– 1470; discussion 1470– 1471. Ellerkmann RM, Cundiff GW, Melick CF, Nihira MA, Leffler K, Bent AE. Correlation of symptoms with location and severity of pelvic organ prolapse. Am J Obstet Gynecol 2001; 185:1332– 1337; discussion 1337– 1338. Barber MD, Cundiff GW, Weidner AC, Coates KW, Bump RC, Addison WA. Accuracy of clinical assessment of paravagin*l defects in women with anterior vagin*l wall prolapse. Am J Obstet Gynecol 1999; 181:87 – 90. Kegel A. The physiologic treatment of urinary stress incontinence. J Urol 1950; 63:808– 814. Theofrastous JP, Swift SE. The clinical evaluation of pelvic floor dysfunction. Obstet Gynecol Clin North Am 1998; 25:783 –804. Sampselle CM, Brink CA, Wells TJ. Digital measurement of pelvic muscle strength in childbearing women. Nurs Res 1989; 38:134 – 138. Sampselle CM, DeLancey JO. The urine stream interruption test and pelvic muscle function. Nurs Res 1992; 41:73– 77. Sampselle CM. Using a stopwatch to assess pelvic muscle strength in the urine stream interruption test. Nurse Pract 1993; 18:14– 16, 18 – 20. Brink CA, Sampselle CM, Wells TJ, Diokno AC, Gillis GL. A digital test for pelvic muscle strength in older women with urinary incontinence. Nurs Res 1989; 38:196 – 199. Layco*ck J. Pelvic muscle exercises: physiotherapy for the pelvic floor. Urol Nurs 1994; 14:136– 140. Toglia MR, DeLancey JO. Anal incontinence and the obstetrician-gynecologist. Obstet Gynecol 1994; 84:731 –740. Peschers UM, Gingelmaier A, Jundt K, Leib B, Dimpfl T. Evaluation of pelvic floor muscle strength using four different techniques. Int Urogynecol J Pelvic Floor Dysfunct 2001; 12:27 – 30. Isherwood PJ, Rane A. Comparative assessment of pelvic floor strength using a perineometer and digital examination. Br J Obstet Gynaecol 2000; 107:1007 – 1011. Crystle CD, Charme LS, Copeland WE. Q-tip test in stress urinary incontinence. Obstet Gynecol 1971; 38:313 –315. Karram MM, Bhatia NN. The Q-tip test: standardization of the technique and its interpretation in women with urinary incontinence. Obstet Gynecol 1988; 71:807 – 811. Bergman A, McCarthy TA, Ballard CA, Yanai J. Role of the Q-tip test in evaluating stress urinary incontinence. J Reprod Med 1987; 32:273 – 275. Montz FJ, Stanton SL. Q-Tip test in female urinary incontinence. Obstet Gynecol 1986; 67:258– 260. Fantl JA, Hurt WG, Bump RC, Dunn LJ, Choi SC. Urethral axis and sphincteric function. Am J Obstet Gynecol 1986; 155:554 – 558. Walters MD, Diaz K. Q-tip test: a study of continent and incontinent women. Obstet Gynecol 1987; 70:208– 211. Fedorkow DM, Sand PK, Retzky SS, Johnson DC. The cotton swab test. Receiver-operating characteristic curves. J Reprod Med 1995; 40:42 – 46. Handa VL, Jensen JK, Ostergard DR. The effect of patient position on proximal urethral mobility. Obstet Gynecol 1995; 86:273 – 276. Bergman A, Koonings PP, Ballard CA. Negative Q-tip test as a risk factor for failed incontinence surgery in women. J Reprod Med 1989; 34:193 – 197. Lobel RW, Sand PK. The empty supine stress test as a predictor of intrinsic urethral sphincter dysfunction. Obstet Gynecol 1996; 88:128 – 132. McLennan MT, Bent AE. Supine empty stress test as a predictor of low Valsalva leak point pressure. Neurourol Urodyn 1998; 17:121 – 127. Fantl JA, Newman DK, Colling J. Urinary incontinence in adults: acute and chronic management. Clinical Practice Guideline, No. 2, 1996 Update. Rockville, MD: U.S. Department of Health and

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Human Services. Public Health Service, Agency for Health Care Policy and Research, March 1996 (vol. AHCPR Publication No. 96-0682). Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30:473 – 483. Shumaker SA, Wyman JF, Uebersax JS, McClish D, Fantl JA. Health-related quality of life measures for women with urinary incontinence: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program in Women (CPW) Research Group. Qual Life Res 1994; 3:291– 306. Uebersax JS, Wyman JF, Shumaker SA, McClish DK, Fantl JA. Short forms to assess life quality and symptom distress for urinary incontinence in women: the Incontinence Impact Questionnaire and the Urogenital Distress Inventory. Continence Program for Women Research Group. Neurourol Urodyn 1995; 14:131 –139. Wagner TH, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of life of persons with urinary incontinence: development of a new measure. Urology 1996; 47:67– 71; discussion 71 – 72. Kelleher CJ, Cardozo LD, Khullar V, Salvatore S. A new questionnaire to assess the quality of life of urinary incontinent women. Br J Obstet Gynaecol 1997; 104:1374 –1349. Jackson S, Donovan J, Brookes S, Eckford S, Swithinbank L, Abrams P. The Bristol female lower urinary tract symptoms questionnaire: development and psychometric testing. Br J Urol 1996; 77:805– 812. Lee PS, Reid DW, Saltmarche A, Linton L. Measuring the psychosocial impact of urinary incontinence: the York Incontinence Perceptions Scale (YIPS). J Am Geriatr Soc 1995; 43:1275– 1278. Rogers RG, Kammerer-Doak D, Villarreal A, Coates K, Qualls C. A new instrument to measure sexual function in women with urinary incontinence or pelvic organ prolapse. Am J Obstet Gynecol 2001; 184:552 –558. Barber MD, Kuchibhatla MN, Pieper CF, Bump RC. Psychometric evaluation of 2 comprehensive condition-specific quality of life instruments for women with pelvic floor disorders. Am J Obstet Gynecol 2001; 185:1388 – 1395. Rockwood TH, Church JM, Fleshman JW. Fecal Incontinence Quality of Life Scale: quality of life instrument for patients with fecal incontinence. Dis Colon Rectum 2000; 43:9 – 16; discussion 16– 17. O’Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology 1997; 49:58– 63. Blaivas JG, Zayed AA, Labib KB. The bulbocavernosus reflex in urology: a prospective study of 299 patients. J Urol 1981;126:197– 199.

9 Urodynamic Assessment: Urethral Pressure Profilometry and PTR Stacey J. Wallach* and Donald R. Ostergard University of California, Irvine, and Long Beach Memorial Medical Center, Long Beach, California, U.S.A.



For a person to be continent, the pressure in the urethra must exceed the pressure in the detrusor at all times. If bladder pressure should overcome urethral pressure, urine loss may result. Researchers have devised different tests to assess the relationship between urethral and bladder pressure. Their goal is to differentiate between patients with urinary incontinence based solely on an anatomic loss of urethral support, from patients with a loss of ability to maintain urethral pressure due to an incompetent urethral sphincter. Both urethral pressure profilometry and leak point pressure look at urethral resistance to voiding. However, urethral pressure profiles are static measurements along the length of the urethra thought to represent the intrinsic sphincter mechanism, while leak point pressures are dynamic tests of the amount of pressure it takes to overcome urethral resistance (1). The female urethra is 3– 4 cm in length and is composed of a longitudinal layer of smooth muscle surrounded by a circular layer of smooth muscle. These smooth muscle layers are, in turn, encompassed by a circular sphincter of striated muscle. Lying beneath the urethral mucosa is a vascular plexus that helps to produce a hermetic seal (2). The striated muscle, the vascular bed, and the smooth muscle and connective tissue together generate the intrinsic urethral pressure. Ulmsten et al. showed that each component is responsible for about a third of the intraurethral pressure (3). Extrinsic factors can further augment urethral pressure. According to DeLancey, the urethra itself lies on a hammock formed by the anterior vagin*l wall (4). By contracting the pelvic diaphragm, the urethra is compressed against the vagin* further augmenting urethral pressures.



In 1923, Victor Bonney (5) became the first person to measure urethral pressures. He used a manometer to determine the pressure required to retrograde infuse fluid into the urethra. Since *Current affiliation: University of California, Sacramento, California, U.S.A. 141


Wallach and Ostergard

that time, various methods to gauge urethral pressure have been devised. In 1940, Barnes (6) used a fluid-filled balloon connected to a pressure transducer to evaluate the urethra’s resistance to distension. In 1957, Lapides and colleagues (7) used a water manometer to quantify urethral wall pressure at specific segments along the urethra. A.

Perfusion Catheters

Brown and Wickham (8) perfected the fluid perfusion technique developed by Toews (9) to create an accurate and reproducible urethral pressure profile. A double- or triple-lumen catheter allowed simultaneous recording of bladder and urethral pressure. Multiple circumferential side holes minimized rotational error. A pump infused fluid at a constant rate of 2 mL/min while a mechanical puller withdrew the catheter 1 –2 mm every second. The transducer measured the pressure of the fluid required to lift the wall of the urethra off the side holes. Later on, other researchers tried carbon dioxide gas as a perfusion medium but this was found to be less accurate (10). (see Fig. 1). B.

Membrane Catheters

The accuracy of perfusion catheters depended on the ability of the urethra to create a seal around the catheter. This shortcoming was remedied with the introduction of membrane catheters in the 1970s. These catheters had a cylindrical balloon or membrane over the infusion holes thus preventing the loss of infusion media. They were more accurate but harder to use (11). All air bubbles needed to be eliminated for accurate readings. The catheter was calibrated to

Figure 1 Perfusion catheter. (A) Before perfusion; (B) during infusion. The catheter measures resistance to flow of the perfusion media. (From Ref. 66, p. 124.)

Urodynamic Assessment


atmospheric pressure prior to insertion. The urethral pressure measured represented the average pressure over the length of the membrane. C.

Microtransducer Catheters

All of the above methods were adequate for recording resting urethral pressure profiles but lacked the ability to accurately measure rapid changes in pressure such as what happens during a cough. In 1973, Millar and Baker (12) developed the microtip transducer. These catheters had a pressure-sensitive piezoelectric unit mounted at the catheter tip and one mounted 6 cm proximal. They were highly sensitive and very accurate and could record dynamic changes in intravesicular pressure and urethral pressure simultaneously. On the downside, they were expensive, extremely fragile, and prone to rotational error since the transducer was unidirectional. In reality, the microtransducer measures a unidirectional force (not pressure) from contact of the piezoelectric unit with the urethral wall (13). D.

Fiberoptic Catheters

Ten years after Millar and Baker (12) developed microtip transducers, Kyarstein and coworkers adapted fiberoptic catheters for urodynamics (14). Fiberoptic catheters were more durable than microtip catheters, did not require orientation, and, like microtip catheters, were able to record dynamic changes in pressure. These catheters were marketed as a reliable and inexpensive way for the average gynecologist/urologist to perform urodynamics. Fiberoptic catheters came in both disposable and reusable forms. However, they tended to record lower than microtip catheters, potentially leading to overdiagnosis of low-pressure urethras (15,16). Some fiberoptic catheters also lacked the ability to record bladder pressure and urethral pressure simultaneously, leaving them vulnerable to error should a bladder contraction occur during the urethral closure pressure profile.



The resting urethral pressure profile is performed with the patient in the sitting position with a full bladder, often immediately after the cystometrogram. As with the cystometrogram, the patient sits in a urodynamic chair. Surface electrodes are placed on either side of the anal sphincter to measure pelvic floor muscle activity. The catheters are calibrated prior to insertion. In the past, the transducers were zeroed at the level of the bladder, but this is no longer necessary with some of the newer catheters. Any prolapse is reduced, with care taken not to apply pressure on the urethra. The intra-abdominal catheter is inserted into the vagin* or rectum and secured. Then the urethral meatus is cleaned and the dual-tipped microtransducer catheter is inserted into the bladder. Before beginning the test, any residual urine is drained and the patient is filled with warm saline to maximum bladder capacity. By convention, the dual-tipped catheter is oriented with the transducer facing 9 o’clock and attached to the mechanical puller device. The mechanical puller is set to withdraw the catheter at a rate between 1 and 2 mm/sec. Orienting the catheter toward 12 o’clock will spuriously elevate urethral pressure, whereas orienting it toward 6 o’clock tends to record lower values (17,18). At the start of the procedure, both transducers on the dual-tipped catheter begin inside the bladder. Therefore, the pressure recorded in the bladder channel should equal the initial pressure recorded in the urethral channel.


Wallach and Ostergard

Once the patient is at maximum bladder capacity, the puller is turned on and the patient is asked to cough to ensure the catheters are recording equally. The catheter is slowly drawn through the urethra by the puller mechanism. The proximal transducer measuring intraurethral pressure will note a progressive increase in pressure from the bladder neck to the midurethra followed by a progressive decrease in pressure to zero as the transducer is pulled past the urethral meatus to outside atmospheric pressure (Fig. 2) This test is repeated to ensure reproducibility, and the results are averaged.

Figure 2 Technique of static urethral pressure profilometry. The study begins with both microtip transducers in the bladder (top), as the catheter is withdrawn through the urethra the proximal transducer records urethral pressure. The urethral pressure increases to maximal urethral pressure near the midurethra (middle), then decreases again (bottom) to zero as the proximal transducer is pulled out of the external meatus to atmospheric pressure. (From Ref. 67, p. 83.)

Urodynamic Assessment




Ideally, when performing a urethral closure pressure profile, six channels are recorded simultaneously—EMG, intravesical pressure, intraabdominal pressure, intraurethral pressure, true detrusor pressure, and urethral closure pressure (Fig. 3). Like true detrusor pressure, urethral closure pressure is a subtracted channel created by deducting intravesical pressure from intraurethral pressure. Thus, the urethral pressure profile differs from the urethral closure pressure profile in that the latter has bladder pressure already subtracted. Rarely, the withdrawal of the catheter through the urethra can cause a detrusor contraction. If bladder pressure is not measured simultaneously with urethral pressure, one may erroneously label the urethral closure pressure as inadequate. The urethral closure pressure profile (UCPP) graphically represents the pressure in the urethra throughout its anatomic length. The maximal urethral closure pressure (MUCP) is the highest amount of pressure attained in the urethra. Thus, the MUCP is the highest point on the urethral closure pressure profile curve (Fig. 4). Anatomically, this point correlates to the area of

Figure 3 The static urethral closure pressure profile in the normal female. Intravesical pressure, intraurethral pressure, and intrarectal pressure are measured simultaneously. The detrusor pressure channel and urethral closure pressure channel are subtracted channels. (From Ref. 66, p. 127.)


Wallach and Ostergard

Figure 4 The static urethral pressure profile with ICS recommended nomenclature in the normal female. (From Ref. 66, p. 646.)

the midurethra where the striated and smooth muscle sphincters overlap. Since the mechanical puller device withdraws the transducer at a set rate, various distances can be calculated. The length from the external urethral meatus to the point of maximum urethral pressure can be determined based on the amount of time it takes the catheter to move from the point of MUCP to the urethral meatus. Functional urethral length and total urethral length can also be measured. Functional urethral length is the length of the urethra along which urethral pressure exceeds bladder pressure. Total urethral length includes the additional length needed to reach atmospheric pressure, but this parameter has not been found to have clinical importance. Investigators have also looked at the area under the urethral closure pressure curve termed the continence area (Fig. 5). This area can be thought of as representing the intrinsic continence mechanism. The space between the urethral closure pressure curve and the zero axis represents the patient’s “margin to leakage,” or the pressure that must be overcome to cause equalization and urine loss. Both the amount of fluid in the bladder and the patient’s position during the test can alter the results of the urethral pressure profile (19 –21). The closure profile of a stress-incontinent patient with a half-full bladder may still show positive pressure with a cough; thus, the patient may not leak. This same person with stress at maximum bladder capacity may lose urine because bladder pressure overcomes urethral pressure. A more upright position creates a larger hydrostatic pressure, which leads to increased activation of urethral and pelvic floor skeletal muscle. This results in higher urethral closure pressures and longer functional urethral lengths. In the continent patient, there is a 25 –70% increase in the maximum urethral closure pressure with standing. This increase is seen primarily in the mid to distal urethra corresponding to the striated sphincter. The patient with genuine stress incontinence has a weakness in her compensatory ability to augment urethral closure pressures by increasing activity of the striated urethral sphincter. For this reason, urethral closure pressures decrease in the stress-incontinent patient as the patient assumes a more upright position (22,23). In addition, other factors may influence urethral closure pressures and functional urethral length. Incontinent patients have lower maximum urethral closure pressures and shorter

Urodynamic Assessment


Figure 5 The static urethral pressure profile in the normal female comparing urethral closure pressure to total urethral pressure. (From Ref. 66, p. 128.)

functional urethral lengths than continent controls, although there is considerable overlap (24,25). Maximum urethral closure pressure and functional urethral length decrease after menopause (26 –28). Both of these parameters increase with the administration of estrogen to postmenopausal women (29,30). Other medications, such as phenylpropanolamine and norephedrine, also increase maximal urethral closure pressure (31,32). On the other hand, various surgeries, e.g., radical hysterectomy, abdominalperineal resection, and internal urethrotomy, have been shown to decrease urethral closure pressure and urethral length (33 –36).


Low Pressure Urethra

In fact, researchers noted that patients who failed previous incontinence procedures were at a higher risk of a subsequent failure (37). McGuire was the first to document that these patients had maximum urethral closure pressures ,20 cmH2O (38,39). Later on, Sand et al. showed that patients with genuine stress incontinence (GSI) and low urethral closure pressures preoperatively were at a higher risk of failure (54% vs. 18% at 3-month follow-up) from a Burch procedure (40). Other researchers concurred with their findings (41,42). Thus, the low-pressure urethra is defined as one in which the maximal urethral closure pressure is 20 cmH2O. This low-pressure urethra is considered to be associated with intrinsic sphincter deficiency. Since patients with low-pressure urethras are at higher risk of surgical failure from traditional retropubic suspension procedures, it is important to diagnose these patients preoperatively. A suburethral sling is the current procedure of choice for these patients with lowpressure urethras. Certain clues in the patient’s history may suggest that further evaluation is necessary to rule out a low-pressure urethra. These include patients with previous failed


Wallach and Ostergard

Figure 6 The static urethral pressure profile superimposed onto a urethra with two diverticulum, one proximal and one distal to the point of maximal urethral pressure. (From Ref. 66, p. 365.)

incontinence procedures, supine urine loss with an empty bladder, urine loss with a change in position, presence of a meningomyelocele (43), previous pelvic radiation (44), history of extensive pelvic surgery such as a radical hysterectomy (33), low anterior resection or abdominalperineal resection (35), or age .50 (45). B.

Double-Peaked UCPPs

The urethral closure pressure profile may also help in detecting urethral kinking, a urethral stricture, diverticulum, or fistula. If a sudden rapid elevation in urethral pressure is visualized during the urethral closure pressure profile, the examiner should be on alert for urethral kinking from a large prolapse or a urethral stricture (46,47). The opposite holds true for a urethral diverticulum or fistula. As the catheter moves over the diverticular ostia or fistula opening, a sudden drop in pressure will occur owing to the absence of the urethral wall. The urethral pressure profile may have a double-peaked or biphasic appearance. Bhatia and coworkers used the urethral closure pressure profile to determine the location of the urethral diverticulum in relationship to the point of maximal urethral pressure (48) (Fig. 6). If the diverticular opening is distal to the peak closure pressure, a Spence procedure can be performed. However, when the diverticular ostia is proximal to the point of maximal closure pressure, a diverticulectomy should be performed since a Spence procedure may result in genuine stress incontinence.



The augmented urethral closure profile reflects the patient’s ability to contract her periurethral and levator ani muscles. This suggests an intact motor pathway from the brain down the spinal cord and out the efferent motor neurons. Patients with motor lesions above the level of the sacral

Urodynamic Assessment


spinal cord cannot control the striated sphincter. These patients lack the ability to relax their external sphincter during voiding, called detrusor sphincter dyssynergia (49). The study is performed in the same manner as the resting urethral closure pressure profile except that the patient is asked to contract the muscles around her urethra as if she is holding her urine while the catheter is withdrawn. Once this is accomplished, the same procedure is performed again with the patient squeezing her rectum while the catheter is withdrawn. With both of these procedures, the maximal urethral closure pressure and functional urethral length should increase if the patient is able to contract her muscles. These tests are analogous to performing a Kegel’s maneuver and are thus dependent on the patient’s understanding the actions requested. Augmented urethral profiles have not been shown to have prognostic value for women undergoing surgery (50).



The dynamic or stress urethral closure pressure profiles reflect the patient’s ability to maintain continence in the face of increases in intraabdominal pressure. In the continent patient, increases in intra-abdominal pressure should be transmitted to both the bladder and proximal/midurethra. (Pressure is not transmitted to the distal urethra because it is below the urogenital diaphragm.) In patients with genuine stress incontinence, the dynamic urethral closure pressure profile equalizes and urine loss occurs in the absence of a detrusor contraction. There are two types of dynamic urethral closure pressure profiles, the Valsalva profile and the cough profile. With the Valsalva profile, the patient is asked to give a maximal Valsalva effort as the catheter is withdrawn through the urethra. The cough profile is performed in the same manner except that the patient is asked to cough every 2 – 3 sec as the catheter is withdrawn (Fig. 7). In both of these tests, the urethral meatus is observed for urine loss. As with static urethral pressure profiles, dynamic urethral pressure profiles are performed at maximum bladder capacity in the sitting position, as patients may be continent at lower bladder volumes. In the continent patient, positive pressure is transmitted to the proximal urethra with each cough. This can be seen as small spikes along the top of the urethral closure pressure profile and represent a negative test. In patients with genuine stress incontinence, less pressure maybe transmitted to the urethra with coughing than the bladder. This represents a failure in the extrinsic continence mechanism, allowing bladder pressure to overcome urethral pressure and urine loss to occur. For the cough urethral pressure profile to be considered positive, the cough spikes must cross the zero axis. When this happens, the pressure in the urethra equalizes with bladder pressure. The functional urethral length is divided into four quarters. Investigators calculate pressure transmission ratios in each quartile by comparing the amount of pressure transmitted to the bladder to the amount of pressure transmitted to the urethra. The pressure transmission ratio is defined as the change in urethral pressure divided by the change in intravesical pressure multiplied by a hundred (Fig. 8). Thus, values .100% imply positive pressure transmission (the urethral pressure spike exceeds the bladder pressure spike), whereas values ,100% suggest that more pressure is transmitted to the bladder than the urethra. As a group, patients with genuine stress incontinence have lower pressure transmission ratios than continent controls (25,51). However, marked overlap exists between pressure transmission ratios in continent and incontinent women, making it difficult to set cutoff values (52,53). That said, most patients with genuine stress incontinence have pressure transmission ratios ,90% (51). Pressure transmission ratios may be useful in excluding genuine stress incontinence, but they lack the sensitivity to diagnose it (low sensitivity, high specificity) (54,55).


Wallach and Ostergard

Figure 7 The cough urethral pressure profile in the continent female (left) and incontinent female (right). The curve on the left shows good pressure transmission with the space under the curve representing this patient’s “margin to leakage.” The curve on the right equalizes with each cough and the patient leaks urine. (From Ref. 67, p. 84.)

Urodynamic Assessment


Figure 8 Calculation of pressure transmission ratios during a cough urethral pressure profile. (From Ref. 68.)


Wallach and Ostergard

No difference in pressure transmission ratios has been demonstrated between patients with genuine stress incontinence and those with low urethral closure pressures (56). Pressure transmission ratios increase after retropubic urethropexies and traditional slings (57 – 61). The improved pressure transmission is theorized to be due to prevention of rotational descent of the urethra (62,63). However, since pressure transmission ratios also increase after the tension-free vagin*l tape procedure, bladder neck support may not be the entire cause for improved transmission ratios (64). Constantinou and colleagues showed that the urethral pressure spike in continent patients precedes the intravesical pressure spike by several hundred milliseconds (65). This relationship is lost in stress-incontinent women even after surgical correction. Thus, there may be an active component to continence as well as the passive transmission of pressure. The urethra may contract closing the bladder neck prior to the increase in bladder pressure.



The micturition urethral closure pressure profile is used to detect outlet obstruction and its location. The catheter is slowly withdrawn through the urethra as the patient voids. This study is used primarily in men to look for obstruction at the bladder neck from a hypertrophied prostate. In the case of obstruction in women, the distal urethra is a more common site. Causes for obstruction in women vary from a urethral stricture, which can result from instrumentation, to urethral kinking from a large prolapse.


ANCILLARY TESTS Bulbocavernosus Reflex

The bulbocavernosus reflex is elicited by tapping the cl*tor*s with a cotton swab. This results in contraction of the bulbocavernosus and ischiocavernosus muscles. With a microtip transducer in the urethra, the bulbocavernosus reflex is detected as a brisk increase in urethral pressure. This reflex depends on the integrity of the pudendal nerve and the sacral spinal cord. B.

Anal Sphincter Reflex

The anal sphincter reflex can also be visualized with a pressure catheter in the urethra. The skin next to the anus is stroked with a Q-tip, eliciting the reflex. An intact reflex indicates normal function of L5 –S2.

REFERENCES 1. 2. 3. 4.

Kohli N, Karram MM. Urodynamic evaluation for female urinary incontinence. Clin Obstet Gynecol 1998; 41:672 –690. DeLancey JO. Anatomy of the female bladder and urethra. In: Ostergard DR, Bent AE, eds. Urogynecology and Urodynamics Theory and Practice. Baltimore: Williams & Wilkins, 1996:5. Rud T, Andersson KE, Asmussen M, Hunting A, Ulmsten U. Factors maintaining the intraurethral pressure in women. Invest Urol 1980; 17:343 – 347. DeLancey JOL. Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis. Am J Obstet Gynecol 1994; 170:1713– 1720.

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Bonney V. On diurnal incontinence of urine in women. J Obstet Gynaecol Br Emp 1923; 30:358– 365. Barnes AC. A method for evaluating the stress of urinary incontinence. Am J Obstet Gynecol 1940; 40:381– 390. Lapides J, Ajemian EP, Stewart BH. Further observations on the kinetics of the urethrovesical sphincter. J Urol 1960; 84:86 –94. Brown M, Wickham JEA. The urethral pressure profile. Br J Urol 1969; 41:211 – 217. Toews H. Intraurethral and intravesical pressure in normal and stress incontinent women. Obstet Gynecol 1967; 29:613 – 624. Gleason DM, Bottaccini MR, Reilly RJ. Comparison of cystourethrograms and urethral profiles with gas and water media. Urology 1977; 9:155– 160. Schmidt RR, Witherow R, Tanagho EA. Recording urethral pressure profile: comparison of methods and clinical implications. Urology 1977; 10:390 – 397. Millar HD, Baker LE. Stable ultraminiature catheter-tip pressure transducer. Med Biol Eng 1973; 11:86– 91. Schafer W. Regarding differences in urethral pressure recordings: contributions from stiffness and weight of the recording catheter. Neurourol Urodyn 1986; 5:119 – 120. Kvarstein B, Aase O, Hansen T, Dobloug P. A new method with fiberoptic transducers used for simultaneous recording of intravesical and urethral pressure during physiological filling and voiding phases. J Urol 1983; 130:504 – 506. Elser DM, London W, Fantl JA, McBride MA, Beck RP. A comparison of urethral profilometry using microtip and fiberoptic catheters. Int Urogynecol J Pelvic Floor Dysfunct 1999; 10:371– 374. Culligan PJ, Goldberg RP, Blackhurst DW, Sasso K, Koduri S, Sand PK. Comparison of microtransducer and fiberoptic catheters for urodynamic studies. Obstet Gynecol 2001; 98:253– 257. Anderson RS, Shepherd Am, Feneley RC. Microtransducer urethral profile methodology: variations caused by transducer orientation. J Urol 1983; 130:727– 728. Masuda H, Yamada T, Nagamatsu H, Nagahama K, Kawakami S, Watanabe T, Negishi T, Morita T. Study of directional differences on static and stress urethral pressure profiles of female urethra. Nippon Himyokika Gakkai Zasshi 1997; 88:40– 45. Jensen JK. Urodynamic evaluation. In: Ostergard DR, Bent AE, eds. Urogynecology and Urodynamics Theory and Practice. 4th ed. Baltimore: Williams and Wilkins, 1996:129 – 130. Abrams PH. Perfusion urethral profilometry. Urol Clin North Am 1979; 6:103– 110. Sorensen S. Urethral pressure variations in healthy and incontinent women. Neurourol Urodyn 1992; 11:549– 591. Tanagho EA, Stoller ML. Urodynamics: cystometry and urethral closure pressure profile. In: Ostergard DR, Bent AD, eds. Urogynecology and Urodynamics Theory and Practice. 3rd ed. Baltimore: Williams and Wilkins, 1991:134. Bhatia NN. Neurourology and urodynamics: sphincter electromyography and electrophysiological testing. In: Ostergard DR, Bent AD, eds. Urogynecology and Urodynamics Theory and Practice. 3rd ed. Baltimore: Williams and Wilkins, 1991:156– 157. Tanagho AE. Urodynamics of female urinary incontinence with emphasis on stress incontinence. J Urol 1979; 122:200– 203. Hilton P, Stanton SL. Urethral pressure measurements by microtransducer: the results in symptomfree women and in those with genuine stress incontinence. Br J Obstet Gynaecol 1983; 90:919– 933. Rud T. Urethral pressure profile in continent women from childhood to old age. Acta Obstet Gyneacol Scand 1980; 59:331 – 335. Tanagho AE, Miller ER. Functional considerations of urethral sphincteric dynamics. J Urol 1973; 109:2273– 2278. Asmussen M. Intraurethral pressure recordings. Scand J Urol Nephrol 1976; 10:1– 6. Rud T. The effects of estrogens and gestagens on the urethral pressure profile in urinary continent and stress incontinent women. Acta Obstet Gynaecol Scand 1980; 59:265 – 270. Hilton P, Stanton SL. The use of intravagin*l oestrogen cream in genuine stress incontinence. Br J Obstet Gynaecol 1983; 90:940 – 944.

154 31.

32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49.

50. 51.

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Wallach and Ostergard Beisland HO, Fossberg E, Moer A, Sander S. Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation. Urol Int 1984; 39:211– 216. Ek A, Andersson KE, Ulmsten U. The effects of norephedrine and bethanechol on the human urethral closure pressure profile. Scand J Urol Nephrol 1978; 12:97– 104. Sasaki H, Yoshida T, Noda K, Yachiku S, Minami K, Kaneko S. Urethral pressure profiles following radical hysterectomy. Obstet Gynecol 1982; 59:101– 104. Farquharson DI, Shingleton HM, Orr JW, Hatch KD, Hester S, Soong SJ. The short-term effect of radical hysterectomy on urethral and bladder function. Br J Obstet Gynaecol 1987; 94:351– 357. Zanolla R, Campo B, Ordesi G, Martino G. Bladder urethral dysfunction after abdominoperineal resection of the rectum for ano-rectal cancer. Tumori 1984; 70:555 – 559. Kessler R, Constantinou CE. Internal urethrotomy in girls and its impact on the urethral intrinsic and extrinsic continence mechanisms. J Urol 1986; 136:1248 – 1253. Stanton SL, Cardozo L, Williams JE, Ritchie D, Allan V. Clinical and urodynamic features of failed incontinence surgery in the female. Obstet Gynecol 1978; 51:515– 520. McGuire EJ, Lytton B, Pepe V, Kohorn EI. Stress urinary incontinence. Obstet Gynecol 1976; 47:255– 264. McGuire EJ. Urodynamic findings in patients after failure of stress incontinence operations. Prog Clin Biol Res 1981; 78:351 – 356. Sand PK, Bowen LW, Panganiban R, Ostergard DR. The low pressure urethra as a factor in failed retropubic urethropexy. Obstet Gynecol 1987; 69:399– 402. Bowen LW, Sand PK, Ostergard DR. Unsuccessful Burch retropubic urethropexy: a case controlled urodynamic study. Am J Obstet Gynecol 1989; 160:451 – 458. Koonings PP, Bergman A, Ballard CA. Low urethral pressure and stress urinary incontinence in women: risk factor for failed retropubic surgical procedure. Urology 1990; 16:245– 248. McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol 1981; 126:205 – 209. Parkin DE, Davis JA, Symonds RP. Urodynamic findings following radiotherapy for cervical carcinoma. Br J Urol 1988; 61:213 – 217. Horbach NS, Ostergard DR. Predicting intrinsic sphincter dysfunction in women with stress urinary incontinence. Obstet Gynecol 1994; 84:188 – 192. Richardson DA, Bent AE, Ostergard DR. The effect of uterovagin*l prolapse on urethrovesical pressure dynamics. Am J Obstet Gynecol 1982; 146:901– 905. Højsgaard A. The urethral pressure profile in female patients with meatal stenosis. Scand J Urol Nephrol 1976; 10:97 – 99. Bhatia NN, McCarthy TA, Ostergard DR. Urethral pressure profiles of women with diverticula. Obstet Gynecol 1981; 58:375 – 378. Steele GS, Sullivan MP, Yalla SV. Urethral pressure profilometry: vesicourethral pressure measurements under resting and voiding conditions. In: Nitti VW, ed. Practical Urodynamics. Philadelphia: W.B. Saunders, 1998:113. Sand PK, Bowen LW, Ostergard DR. The prognostic significance of augmentation of urethral closure pressure and functional urethral length. Int J Gynaecol Obstet 1990; 33:135 – 139. Bump RC, Copeland WE, Hurt WG, Fantl JA. Dynamic urethral pressure/profilometry pressure transmission ratio determinations in stress-incontinent and stress-continent subjects. Am J Obstet Gynecol 1988; 159:749 – 755. Rosenzweig BA, Bhatia NN, Nelson AL. Dynamic urethral pressure profilometry pressure transmission ratios: what do the numbers really mean? Obstet Gynecol 1991; 77:586 – 590. Lose G, Thind P, Colstrup H. The value of pressure transmission ratio in the diagnosis of stress incontinence. Neurourol Urodyn 1990; 9:323 – 324. Richardson DA. Value of the cough pressure profile in the evaluation of patients with stress incontinence. Am J Obstet Gynecol 1986; 155:808 – 811. Hanzal E, Berger E, Koelbl H. Reliability of the urethral closure pressure profile during stress in the diagnosis of genuine stress incontinence. Br J Urol 1991; 68:369 –371.

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58. 59.


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Summitt RL, Sipes DR, Bent AE, Ostergard DR. Evaluation of pressure transmission ratios in women with genuine stress incontinence and low urethral pressure: a comparative study. Obstet Gynecol 1994; 83:984 –988. Faysal MH, Constantinou CE, Rother LF, Govan DE. The impact of bladder neck suspension on the resting and stress urethral pressure profile: a prospective study comparing controls with incontinent patients preoperatively and postoperatively. J Urol 1981; 125:55 –60. Hilton P, Stanton SL. A clinical and urodynamic assessment of the Burch colposuspension for genuine stress incontinence. Br J Obstet Gynaecol 1983; 90:934 – 939. Weil A, Reyes H, Bischoff P, Rottenberg RD, Krauer F. Modifications of the urethral rest and stress profiles after different types of surgery for urinary stress incontinence. Br J Obstet Gynaecol 1984; 91:46– 55. Beck RP, McCormmick S, Nordstrom L. Intraurethral-intravesical cough-pressure spike differences in 267 patients surgically cured of genuine stress incontinence of urine. Obstet Gynecol 1988; 72:302– 306. Baker KR, Drutz HP. Retropubic colpourethropexy: clinical and urodynamic evaluation in 289 cases. Int Urogyncol J 1991; 2:196 – 200. Bunne G, Obrink A. Influence of pubococcygeal repair on urethral closure pressure at stress. Acta Obstet Gynaecol Scand 1978; 57:355– 359. Barbic M, Kralj B. Effect of intra-abdominal position of the bladder neck and stability of its supporting structures on pressure transmission ratio after colposuspension. Int Urogynecol J Pelvic Floor Dysfunct 2000; 11:97 – 102. Mutone N, Mastropietro M, Brizendine E, Hale D. Effect of tension-free vagin*l tape procedure on urodynamic continence indices. Obstet Gynecol 2001; 98:638 –645. Constantinou CE, Govan DE. Spatial distribution and timing of transmitted and reflexly generated urethral pressures in healthy women. J Urol 1982; 127:964 – 969. Ostergard DR, Bent AD, eds. Urogynecology and Urodynamics Theory and Practice, 4th ed. Baltimore: Williams & Wilkins, 1996. Walters MD, Karram MM, eds. Urogynecology and Reconstructive Pelvic Surgery, 2nd ed. St. Louis: Mosby, 1999. Karram MM. Urodynamics. In: Benson JT, ed. Female pelvic floor disorders: Investigation and management. New York: Norton Medical Books, 1992.

10 Leak Point Pressures Shahar Madjar Northern Michigan Urology at Bell, Bell Memorial Hospital, Marquette County, Michigan, U.S.A.

Rodney A. Appell Baylor College of Medicine, Houston, Texas, U.S.A.



The concept of leak point pressure (LPP) determination was introduced by McGuire et al. (1). The first LPP to be defined was the detrusor or bladder leak point pressure (DLPP) and was correlated with an increased risk of upper tract deterioration in children with meningomyelocele (1). The definition of abdominal LPP (ALPP) was to follow (2), and it was used to categorize patients into either anatomical or intrinsic sphincteric deficiency (ISD), the two types of stress urinary incontinence. ALPPs can be further divided to ALPP measured during Valsalva maneuver (VLPP) and ALPP measured during cough (CLPP). There is lack of standardization of how LPPs are measured. Different entities of LPP and a great variation in the techniques used to measure each of these entities have led to considerable confusion among professionals. The clinical applicability of these tests is therefore still controversial, and interpretation of results is difficult. The definitions of LPP, the techniques used for their measurement, and their clinical applicability are described and discussed.



The following definitions were made by the Standardization Committee of the International Continence Society (ICS) and approved at the 28th annual meeting of the society in Jerusalem (3). Detrusor leak point pressure is the lowest value of detrusor pressure at which leakage is observed in the absence of abdominal strain or a detrusor contraction. It is described as a static or passive test to assess the storage function and detrusor compliance, particularly in patients with neurogenic lower tract dysfunction. Abdominal leak point pressure is the lowest of the intentional or actively increased intravesical pressure that provokes urinary leakage in the absence of detrusor contraction. Increased abdominal pressure can be induced by coughing (CLPP) or by a Valsalva maneuver 157


Madjar and Appell

(VLPP). ALPP is a dynamic test used to assess the severity and the type (anatomical vs. ISD) of stress urinary incontinence. The pressure measured in the bladder (Pves) is equal to the abdominal pressure plus the pressure produced by the detrusor itself (Pves ¼ Pabd þ Pdet). ALPP is defined as an intravesical pressure measurement at a time where no detrusor contraction appears (change in Pdet ¼ 0). Therefore, the change in pressure measured at the bladder will be equal to that measured in the abdomen (Pves ¼ Pabd). ALPP can thus be determined with no pressure measurement probe in the bladder. This may allow for a true measurement of ALPP without interference of a urethral catheter partially obstructing the bladder outlet.





Various techniques have been described to measure LPPs. These variations affect the actual readings of LPP values. It is therefore recommended by the ICS that the location and access of pressure sensors, position of the patient, the method by which the bladder is filled (diuresis or catheter), and the volume at which the measurement is performed (both absolute and in relation to maximum cystometric capacity) be specified. The mode of leak detection (e.g., direct or fluoroscopic observation), the catheters used, and the measuring equipment for pressure measurement should also be reported. ALPP measurement is usually performed during urodynamic testing after cystometrography with an intraurethral catheter. Rectal or vagin*l pressure sensors can be alternatively used to prevent interference of the urethral catheter with urinary leakage. The bladder is filled to 200 mL, 250 mL, 50% of maximum cystometric capacity, or another predetermined fixed volume. The patient is then asked to gradually increase his/her intra-abdominal pressure (in the case of VLPP measurement) or to cough several times with increasing strength (CLPP). Some laboratories use CLPP only when Valsalva maneuver has failed to produce leakage. The lowest abdominal or vesical pressure at which leakage occurs is recorded and interpreted as ALPP. Leakage can be detected using visual recording (4 – 6), video or fluoroscopy (1,7,8), or electric conductance (9 – 11). B.

Study Conditions

Several factors have been described as influencing ALPP measurement and interpretation. The following are variations and modifications in the technique used to measure ALPP and their effect on ALPP values. 1. Catheter VLPP measured by a urethral catheter was found to be higher than that measured with a rectal catheter (12). This may result from the catheter’s partially occluding the bladder outlet. Catheter size also affects LPP results, with larger-diameter catheters correlating with higher VLPP measurement (4, 13). In a recent report by Bump et al., VLPP measurements were significantly higher when an 8Fr catheter was used compared with a 3Fr catheter (4). 2.

Bladder Volume

VLPP is correlated with bladder volume in the majority of clinical studies. Theofrastous (14) reported on 120 women with genuine stress urinary incontinence who underwent serial VLPP

Leak Point Pressures


determinations at bladder volumes of 100, 200, and 300 mL, and at maximum cystometric capacity. Thirty-three women had leakage starting at a vesical volume of 100 mL, 18 at 200 mL, 19 at 300 mL, and 17 had leakage only at maximum cystometric capacity. The mean first positive VLPPs were significantly higher than VLPPs at maximum capacity in all groups. It was concluded that VLPP in women with stress urinary incontinence decreases significantly with bladder filling. This was supported by the findings reported by Faerber and Vashi (15). Still others found no correlation between bladder volumes (150, 300, maximal cystometric capacity) and VLPP (16). 3. Cough Versus Valsalva Leak Point Pressures Both Valsalva maneuver and cough have been used to provoke leakage in the determination of ALPP. Peschers et al. (17) reported on their evaluation in 59 incontinent women: CLPP was found to be significantly higher than VLPP (112.5 + 46.9 cm water vs. 58.9 + 27.6, P , .0001). While CLPP was negative in two women only, VLPP was negative in 24 of 59 women evaluated (40.1%). If intrinsic sphincter deficiency (ISD) was defined as a leak point pressure of 65 cm water, 16.9% of women fulfilled this criterion using the CLPP compared to 35.6% when VLPP is used. Therefore, coughing and Valsalva maneuver result in a different classification of stress urinary incontinence into ISD and anatomical stress incontinence. A similar correlation between CLPP and VLPP values was reported by Bump et al. (4). 4.

Interpretation of Results

One of the debates concerning interpretation and the clinical applicability of VLPP measurements is how they should be read. Should only the increase in intravesical pressure (Pves) over baseline resting Pves (DVLPP) be accepted in the interpretation of the urodynamic tracing or should the total increase in Pves (VLPPtot), meaning the resting baseline Pves þ the increase in Pves during Valsalva, be accepted in the interpretation of urodynamic tracing? Madjar et al. (18) studied 264 female patients who had undergone an anti-incontinence procedure. Baseline Pabd varied between 10 and 55 cmH2O (mean ¼ 32.7 + 8.8) and was significantly correlated with patient’s weight (P , .001) and patient’s body mass index (P , .001). Higher VLPPtot significantly correlated with decreased age (P ¼ .004), less severe incontinence (P ¼ .004), higher peak Valsalva pressure (P , .0001), and the ability to increase abdominal pressure for a longer period of time (time to peak Pabd during Valsalva). VLPPtot and DVLPP had similar statistical correlation with all the clinical variables examined, and neither could predict the outcome of any anti-incontinence surgery. Using a VLPP of 60 cmH2O as a cutoff to differentiate severe ISD from anatomical incontinence, 211 (67.4%) of the patients would be categorized as having ISD according to their DVLPP, compared with only 106 (40.1%) using the VLPPtot. Looking at VLPPtot and DVLPP will therefore result in a different categorization of the type of incontinence in at least 25% of patients. 5.

Alternatives to ALPP Measurement

Supine stress tests at empty bladder and at 200 mL were suggested as alternatives to the VLPP measurement by McLennan (19) and Hsu et al. (20), respectively. McLennan reported on 179 patients with a history of genuine stress incontinence confirmed with urodynamic testing. All patients had a supine stress test performed after voiding. Residual urine determinations were all ,100 cc. A vesical Valsalva leak point pressure determination (cough and strain) was performed during multichannel urodynamics with 150 cc in the bladder. A statistically significant relationship between a low leak point pressure and a positive supine


Madjar and Appell

empty stress test (P , .000) was found. The supine empty stress test had a sensitivity of 79% and a specificity of 62.5% for the detection of a low leak point pressure. The negative predictive value was high at 90%. Hsu et al. (20) reported on their experience with a supine stress test performed at a bladder volume of 200 mL. Cough and Valsalva maneuvers were performed after bladder filling to 200 mL with sterile normal saline solution by gravity. Efflux of the bladder solution from the meatus coinciding with the cough or Valsalva maneuver was defined as a positive clinical test. ISD was defined as an ALPP of ,100 cmH2O, and the supine stress test had 93.5% sensitivity, 90.0% specificity, 96.7% positive predictive value, and 81.8% negative predictive value for detecting ISD. It was concluded that the supine stress test is easy, quick, and inexpensive, and a positive test is a reliable predictor of ISD.




Female Stress Urinary Incontinence

Urethral pressure measurements, such as maximal urethral closing pressure, have been frequently and extensively used to assess urethral sphincteric deficiency (21 – 23). Despite a great deal of evidence to the contrary, maximal urethral pressure measurements have been considered by many to be closely related to continence function. This theory was challenged by McGuire et al. (2), who in 1993 reported on results comparing MUCP with ALPP. One hundred twenty-five women were divided into three types of stress urinary incontinence according to their proximal urethral closing pressure and the degree of rotational descent of the urethra (no rotation, 458 rotation, and .458 rotation). Patients with low abdominal leak point pressure (,60 cmH2O) had more severe incontinence, with 75% of them having type 3 incontinence (low urethral pressure, no urethral hypermobility). Patients with high ALPP (.90 cmH2O) showed a lesser degree of incontinence and were classified as having only types 1 or 2 of incontinence (high urethral pressure and minimal or gross hypermobility, respectively). The middle group (ALPP 60– 89 cmH2O) had either type 2 or type 3 stress urinary incontinence. ALPPs were therefore correlated with the type of incontinence. However, abdominal pressures required to cause stress incontinence were unrelated to maximum urethral pressure, which indicates that maximum urethral pressure has little relationship with urethral resistance to abdominal pressure. This correlation between low ALPP values and ISD has been confirmed by others (24 – 26). The value of distinguishing between ISD and anatomical incontinence is based primarily on different treatment modalities allocated for different types of incontinence. Traditionally, sling procedures, injectable bulking agents, and artificial urinary sphincters have been used for the treatment of ISD, while other treatment modalities, such as suspension procedures, have been used for the treatment of anatomical incontinence. This concept has recently been challenged. A considerable overlap exists between these entities (27,28). Moreover, treatments such as sling procedures, which were traditionally used for the treatment for ISD, are reported to be as effective for anatomical incontinence (29). In light of these facts, the true value of ALPP determinations and the categorization of patients into anatomic and ISD types of incontinence are still to be determined. B.

Postprostatectomy Incontinence

VLPP has been extensively used as a research tool in studies on the pathophysiology of postprostatectomy incontinence. Desautel et al. (30) report their findings in 39 (35 radical, 4 TURP and radiation) patients referred for evaluation of incontinence after prostatectomy.

Leak Point Pressures


Sphincteric damage was found to be the sole cause of urinary incontinence in 23 patients (59%) and a major contributor in 14 others (36%). Twenty-seven patients (69%) had VLPP ,103 cmH2O (mean ¼ 55) with a urethral urodynamic catheter in place. An additional 10 (26%) had VLPP ,150 cmH2O (mean ¼ 63) upon removal of the catheter. VLPP is suggested as an indication of the severity of sphincteric damage. The importance of removing the urodynamic catheter during measurement of the VLPP was emphasized. Bladder dysfunction characterized by detrusor instability and/or decreased bladder compliance was seen in 15 patients (39%). Thus, in this group of patients, incontinence was mainly due to sphincteric damage. The severity of incontinence was correlated with VLPP values. Winters et al. (31) reported similar results in 92 patients with incontinence at least 1 year after prostatectomy (65 patients [71%] after radical prostatectomy [RP] and 27 patients [29%] after transurethral resection of the prostate or TURP). Valsalva leak point pressures (VLPP) were measured in the absence of a bladder contraction at a 150-mL volume and at 50-mL increments thereafter until maximum functional capacity was reached. The predominant urodynamic finding was sphincteric incompetence, as VLPPs were obtained in 85 patients (92%) and ranged from 12 to 120 cmH2O. Detrusor overactivity was a common finding and occurred in 34 patients (37%); however, it was found to be the sole cause of incontinence in only three patients (3.3%). There was no statistically significant difference in the incidence of sphincteric incompetence after RP or TURP; however, TURP patients had a higher incidence of detrusor overactivity, which was statistically significant (P ¼ .019). No correlation was found between the severity of incontinence (measured by preoperative pad usage) and VLPP. It was concluded that, although bladder dysfunction may be contributing problem in patients with postprostatectomy incontinence, it is rarely the only mechanism for this disorder. Since bladder dysfunction may coexist or be the sole cause of postprostatectomy incontinence, urodynamic studies are important to define the exact cause(s) of incontinence after prostatectomy. Gudziak et al. (32) examined the relationship between maximum urethral pressure, which was measured at the level of the membranous urethra, or extrinsic urethral sphincter function, and abdominal leak point pressure in 27 men with postprostatectomy incontinence. No correlation was found between maximum urethral and abdominal leak point pressures. Extrinsic urethral sphincter function was normal in all patients, while all patients but one had evidence of ISD. It is suggested that postprostatectomy stress incontinence is caused by sphincter dysfunction due to ISD and is not correlated with extrinsic sphincteric function, or maximal urethral pressure.


Urinary Diversion

Leak point pressure was used as part of the evaluation of bilateral hydroureteronephrosis following ileal conduit urinary diversion by Knapp et al. (33) A conduit urodynamic study was used to evaluate conduit function with a triple-lumen urodynamic catheter to simultaneously measure conduit pressure proximal and distal to the fascia during filling under fluoroscopy. In four control patients with normal upper tracts, conduit leak point pressures ranged from 5 to 20 cmH2O. Abnormalities were found in five of six patients with bilateral hydroureteronephrosis. These included functional stomal stenosis in two patients, an atonic loop in one patient, segmental obstruction in one patient, and a high-pressure, noncompliant distal segment in one patient. It is concluded that loop urodynamics can serve as a useful tool in the evaluation of postoperative bilateral hydronephrosis. Leak point pressures were also used to evaluate the postoperative continence status in women who had undergone modified nerve sparing radical cystectomy and creation of an ileal orthotopic neobladder (34).


Madjar and Appell

Intraoperative use of LPP measurements have been attempted to adjust the continence mechanism and thus insure adequate continence after cutaneous urinary diversion (35). Intraoperative LPP was measured before detubularization using a simple standing column manometer and arterial line tubing. Whenever leakage occurred at pressure ,75 –80 cmH2O, the continence mechanism was adjusted and LPP measurement was repeated to ensure adequate continence. Seventy-seven patients participated in the study. Adjustment of the continence mechanism was required in 32 of the 41 patients in whom the native appendicocolic junction was used and in all 36 patients in whom the tapered ileum and ileocecal valve were used. After adjustment, all patients attained leak pressures .80 cmH2O. With a follow-up period of 30– 100 months, all 77 patients were continent on an intermittent catheterization program and none has required revision of the continence mechanism. Leak point pressures have been also used to evaluate operative success of incontinent ileovesicostomies in tetraplegic patients (36). Postoperative urodynamics demonstrated subjects (n ¼ 7) to have a mean stomal leak point pressure of 7.7 cmH2O (range 5– 10). In follow-up of 12– 15 months, no patient demonstrated calculus formation, hydronephrosis, autonomic dysreflexia, or worsening renal function.





For DLPP determination, the bladder is first emptied. Bladder filling is performed at 60 mL/min in adults and at up to 20 mL/min in children. Bladder pressure is measured while the urethral meatus is observed for leakage. The study is completed once a Pdet of 40 cmH2O is reached, leakage is observed, a detrusor contraction occurs, or the maximum volume recovered at a few episodes of intermittent catheterization is reached (37). B.

Clinical Application

In 1981 McGuire et al. (1) reported the clinical progress of 42 myelodysplastic patients studied urodynamically and followed for a mean of 7.1 years. DLPP was 40 cmH2O or less in 20 patients and .40 cmH2O in 22 patients. No patient in the low-pressure group had vesicoureteral reflux, and only two patients showed ureteral dilatation on excretory urography. In contrast, of the patients in the higher-pressure group 15 (68%) showed vesicoureteral reflux, and 18 (81%) showed ureteral dilatation on excretory urography. Thus, a striking relationship between intravesical pressure at the time of urethral leakage and the clinical course in this group of myelodysplastic patients was demonstrated. A new modification of the technique used to measure detrusor leak point pressure in patients with myelodysplasia was later introduced by Combs and Horowitz (38). DLPP is measured during standard multichannel urodynamics. Once leakage occurs, DLPP is recorded and the catheter is removed. With the cessation of leakage, the catheter is reinserted and detrusor pressure is again noted. This cycle is repeated several times, and the average difference is noted. Fifty-four patients in whom leakage occurred were included in this study. Three groups of patients were identified: (a) (20 patients)—detrusor leak point pressure .40 and ,40 cmH2O with the catheter in and out, respectively; (b) (29 patients)—detrusor leak point pressure consistently ,40 cmH2O with the catheter in and out; and (c) (five patients)—detrusor leak point pressure consistently .40 cmH2O with the catheter in and out. All patients in group (b) had normal upper tracts. Although detrusor leak point pressure was .40 cmH2O using standard measurement techniques in both groups (a) and (c), upper-tract changes were demonstrated in

Leak Point Pressures


40% of patients in group (c) but only in 5% of patients in group (a). This modification is suggested as a more accurate measurement of DLPP and a better means of identifying patients at increased risk for renal deterioration. The main critique of this study is the low number of participants in group (c), making comparison between groups (a) and (c) difficult. Kim et al. (39) have demonstrated that DLPP of 40 cmH2O is also useful in the case of transurethral resection of the external sphincter in patients with spinal cord injury and detrusorexternal sphincter-dyssynergia (DSD). DLPP was retrospectively analyzed in 55 spinal cord injury patients who had undergone transurethral resection of the external sphincter. Patients with DLPP .40 cmH2O had a significantly higher incidence of upper-tract damage (P ¼ .021) and persistent DSD (P ¼ .00008). DLPP .40 cmH2O is therefore suggested as a valid indicator of failure of transurethral resection of the external sphincter procedure. DLPP has been widely used in other instances as a outcome measure of various operative procedures to treat neurogenic bladder such as external sphincterotomy (40), external sphincter dilatation (41), and combination therapy of intermittent catheterization and oral anticholinergic medications (42).



Both ALPP and DLPP have been extensively studied. DLPP is a valuable tool in identifying patients at increased risk for upper-tract deterioration. ALPP is used to determine the severity of stress urinary incontinence and to categorize patients with stress urinary incontinence into anatomical and ISD types of incontinence. The clinical value of ALPP will be determined by standardization of technique and interpretation. Future determination of the need to categorize patients into ISD and anatomical types of stress urinary incontinence will also have an impact on the clinical value of ALPP.



5. 6.



McGuire EJ, Woodside JR, Borden TA, Weiss RM. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol 1981; 126:205. McGuire EJ, Fitzpatrick CC, Wan J, Bloom D, Sanvordenker J, Ritchey M, Gormley EA. Clinical assessment of urethral sphincter function. J Urol 1993; 150:1452. Stohrer M, Goepel M, Kondo A, Kramer G, Madersbacher H, Millard R, Rossier A, Wyndaele JJ. The standardization of terminology in neurogenic lower urinary tract dysfunction: with suggestions for diagnostic procedures. International Continence Society Standardization Committee. Neurourol Urodyn 1999; 18:139. Bump RC, Elser DM, Theofrastous JP, McClish DK. Valsalva leak point pressures in women with genuine stress incontinence: reproducibility, effect of catheter caliber, and correlations with other measures of urethral resistance. Continence Program for Women Research Group. Am J Obstet Gynecol 1995; 173:551. Sultana CJ. Urethral closure pressure and leak-point pressure in incontinent women. Obstet Gynecol 1995; 86:839. Van Venrooij GE, Blok C, van Riel MP, Coolsaet BL. Relative urethral leakage pressure versus maximum urethral closure pressure. The reliability of the measurement of urethral competence with the new tube-foil sleeve catheter in patients. J Urol 1985; 134:592. Hernandez RD, Hurwitz RS, Foote JE, Zimmern PE, Leach GE. Nonsurgical management of threatened upper urinary tracts and incontinence in children with myelomeningocele. J Urol 1994; 152:1582. McGuire EJ. Urodynamic evaluation of stress incontinence. Urol Clin North Am 1995; 22:551.

164 9. 10. 11. 12. 13. 14. 15. 16. 17. 18.

19. 20. 21. 22. 23. 24.

25. 26. 27. 28.

29. 30. 31. 32. 33. 34.

Madjar and Appell Plevnik S, Vrtacnik P, Janez J. Detection of fluid entry into the urethra by electric impedance measurement: electric fluid bridge test. Clin Phys Physiol Meas 1983; 4:309. Plevnik S, Brown M, Sutherst JR, Vrtacnik P. Tracking of fluid in urethra by simultaneous electric impedance measurement at three sites. Urol Int 1983; 38:29. Sutherst J, Brown M. The fluid bridge test for urethral incompetence. A comparison of results in women with incontinence and women with normal urinary control. Acta Obstet Gynaecol Scand 1983; 62:271. Payne CK, Raz S, Babiarz JW. The Valsalva leak point pressure in evaluation of stress urinary incontinence. Technical aspects of measurements. J Urol 1994; 151:478 [Abstract]. Decter RM, Harpster L. Pitfalls in determination of leak point pressure. J Urol 1992; 148:588. Theofrastous JP, Cundiff GW, Harris RL, Bump RC. The effect of vesical volume on Valsalva leakpoint pressures in women with genuine stress urinary incontinence. Obstet Gynecol 1996; 87:711. Faerber GJ, Vashi AR. Variations in Valsalva leak point pressure with increasing vesical volume. J Urol 1998; 159:1909. Petrou SP, Kollmorgen TA. Valsalva leak point pressure and bladder volume. Neurourol Urodyn 1998; 17:3. Peschers UM, Jundt K, Dimpfl T. Differences between cough and Valsalva leak-point pressure in stress incontinent women. Neurourol Urodyn 2000; 19:677. Madjar S, Balzarro M, Appell RA, Tchetgen MB, Nelson D. Baseline abdominal pressure and Valsalva leak point pressures—correlation with clinical and urodynamic data. Neurourol Urodyn 2003; 22:2–6. McLennan MT, Bent AE. Supine empty stress test as a predictor of low Valsalva leak point pressure. Neurourol Urodyn 1998; 17:121. Hsu TH, Rackley RR, Appell RA. The supine stress test: a simple method to detect intrinsic urethral sphincter dysfunction. J Urol 1999; 162:460. Awad SA, Bryniak SR, Lowe PJ, Bruce AW, Twiddy DA. Urethral pressure profile in female stress incontinence. J Urol 1978; 120:475. Brown M, Wickham JE. The urethral pressure profile. Br J Urol 1969; 41:211. Hilton P, Stanton SL. Urethral pressure measurement by microtransducer: the results in symptom-free women and in those with genuine stress incontinence. Br J Obstet Gynaecol 1983; 90:919. Bump RC, Coates KW, Cundiff GW, Harris RL, Weidner AC. Diagnosing intrinsic sphincteric deficiency: comparing urethral closure pressure, urethral axis, and Valsalva leak point pressures. Am J Obstet Gynaecol 1997; 177:303. Haab F, Zimmern PE, Leach GE. Female stress urinary incontinence due to intrinsic sphincteric deficiency: recognition and management. J Urol 1996; 156:3. Nitti VW, Combs AJ. Correlation of Valsalva leak point pressure with subjective degree of stress urinary incontinence in women. J Urol 1996; 155:281. Dietz HP, Herbison P, Clarke B. The predictive value of hypermobility and urethral closure pressure in the diagnosis of female stress urinary incontinence. Neurourol Urodyn 2001; 20:490. Madjar S, Balzarro M, Appell RA. Urethral hypermobility and intrinsic sphincteric deficiency— separate entities or coexisting factors in women with stress urinary incontinence. J Urol 2002 [Abstract]. Zaragoza MR. Expanded indications for the pubovagin*l sling: treatment of type 2 or 3 stress incontinence. J Urol 1996; 156:1620. Desautel MG, Kapoor R, Badlani GH. Sphincteric incontinence: the primary cause of postprostatectomy incontinence in patients with prostate cancer. Neurourol Urodyn 1997; 16:153. Winters JC, Appell RA, Rackley RR. Urodynamic findings in postprostatectomy incontinence. Neurourol Urodyn 1998; 17:493. Gudziak MR, McGuire EJ, Gormley EA. Urodynamic assessment of urethral sphincter function in post-prostatectomy incontinence. J Urol 1996; 156:1131. Knapp PM Jr, Konnak JW, McGuire EJ, Savastano JA. Urodynamic evaluation of ileal conduit function. J Urol 1987; 137:929. Aboseif SR, Borirakchanyavat S, Lue TF, Carroll PR. Continence mechanism of the ileal neobladder in women: a urodynamics study. World J Urol 1998; 16:400.

Leak Point Pressures 35. 36. 37. 38. 39.

40. 41.



Bissada NK, Marshall I. Leak point pressure use for intraoperative adjustment of the continence mechanism in patients undergoing continent cutaneous urinary diversion. Urology 1998; 52:790. Mutchnik SE, Hinson JL, Nickell KG, Boone TB. Ileovesicostomy as an alternative form of bladder management in tetraplegic patients. Urology 1997; 49:353. McGuire EJ, Cespedes RD, O’Connell HE. Leak-point pressures. Urol Clin North Am 1996; 23:253. Combs AJ, Horowitz M. A new technique for assessing detrusor leak point pressure in patients with spina bifida. J Urol 1996; 156:757. Kim YH, Kattan MW, Boone TB. Bladder leak point pressure: the measure for sphincterotomy success in spinal cord injured patients with external detrusor-sphincter dyssynergia. J Urol 1998; 159:493. Juma S, Mostafavi M, Joseph A. Sphincterotomy: long-term complications and warning signs. Neurourol Urodyn 1995; 14:33. Park JM, McGuire EJ, Koo HP, Schwartz AC, Garwood CK, Bloom DA. External urethral sphincter dilation for the management of high risk myelomeningocele: 15-year experience. J Urol 2001; 165:2383. Pannek J, Diederichs W, Botel U. Urodynamically controlled management of spinal cord injury in children. Neurourol Urodyn 1997; 16:285.

11 Videourodynamics Jennifer Gruenenfelder and Edward J. McGuire University of Michigan, Ann Arbor, Michigan, U.S.A.



The patient with complaints of urinary incontinence or urinary retention cannot be diagnosed reliably on the basis of history and physical alone. Urodynamics is an attempt to measure bladder and urethral function objectively. Videourodynamics adds anatomic detail to these measurements with the addition of a fluoroscopy unit, which allows real time imaging of the bladder and urethra during filling and voiding. The information obtained is useful for both the diagnosis and prognosis of urologic disease. Urologic disease may result from a number of different etiologies. Neurologic diseases are associated with bladder and urethral dysfunction, and generalizations can be made about the type of dysfunction based upon the type of disease and the level of the lesion. These inferences are not reliable. For example, among patients with spinal cord injury, we assume the following: Cervical injury is associated with detrusor external sphincter dyssynergia (DESD); thoracic injury is associated with detrusor hyperreflexia (DH) and DESD; and lumbar and sacral injuries are associated with detrusor areflexia (DA). Kaplan et al. (1) showed that although these generalizations are largely true. There are statistically significant numbers of patients with cervical injury who have DA and patients with sacral injury with DESD. Patients with thoracic and lumbar lesions had even greater variation in their urodynamic findings in the same study. This study shows clearly why individual patients require urodynamic testing rather than making treatment plans based on assumptions about dysfunction from the level of the lesion. Chancellor et al. (2) showed that even patients with incomplete injuries to the thoracolumbar spine often have occult neurogenic bladder dysfunction, including 41% of patients with ASIA E impairment (otherwise completely neurologically intact). Similarly, one cannot infer bladder dysfunction based on MRI findings of the anatomical lesion of multiple sclerosis (3). The patterns of dysfunction in patients with neurogenic bladder dysfunction caused by MS change over time, which means that urodynamics has a role not only in initial diagnosis but also in managing patients with multiple sclerosis as it progresses (4). Clearly, urodynamic monitoring is also important for diagnosis and prognosis of the neurogenic bladder associated with myelodysplasia (5 – 7). It is from this patient population that we have drawn many of our assumptions about the long-term prognosis of patients with poorly managed neurogenic bladders. 167


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The use of urodynamics is not limited to investigating the urologic manifestations of neurologic disease. Its role has been delineated in the diagnosis of diseases of otherwise healthy patients such as stress incontinence (8,9), benign prostatic hyperplasia (10,11), diabetic cystopathy (12), vesicoureteral reflux (13,14), and incontinence resulting from surgical or radiation injury (15 – 18). Thus, videourodynamics is an important tool in the diagnosis and treatment of patients with a wide range of urological complaints. This chapter will describe the basics of videourodynamics with some clinical applications to demonstrate its utility.



The cystometrogram (CMG) is a measurement of bladder pressure during filling. A catheter with a pressure transducer in its tip is placed into the bladder. There are a number of catheters available. We prefer a triple-lumen catheter with pressure transducers placed to measure the bladder and urethral pressure simultaneously (19 – 21). A rectal balloon with a pressure transducer is also placed. The bladder is filled with saline, contrast dye, or carbon dioxide at variable fill rates. We prefer a liquid infusion because leakage is more obvious and because the gas can be irritating to the bladder wall (22). Pves is the measure of the bladder pressure during filling. Pabd is the abdominal pressure measured by the rectal catheter. Pdet is the difference, Pves –Pabd, and it is thought to be a measure of pure detrusor pressure. Although the subtracted difference may give a more accurate measurement of pure detrusor function, many investigators feel that Pves is sufficient clinical information, particularly in patients with high spinal cord lesions who are unlikely to generate high abdominal pressures (23,24). We fill at a flow rate of 50 cc/min. The rate of filling should be slower in patients with detrusor hyperactivity and in children. The patients are asked to note the first sensation and the point at which they would normally void. Sensation is thus a tool in measuring bladder function. First sensation, first desire to void, and strong desire to void are reproducible, and there is a normal pattern to them that likely corresponds with physiology (25). Delayed sensation can be seen in many disease processes (12,17,26,27). Early sensation may indicate sensory urgency or interstitial cystitis, although it often occurs simply as an artifact of filling the bladder with solution colder than body temperature. Capacity is the volume the patient is able to tolerate before he needs to void. This is partially a subjective measurement as it also reflects bladder sensation. Typically the awake bladder capacity is measured, although CMG can also be performed on patients receiving general anesthesia. Functional bladder capacity is more accurately measured with a careful voiding diary. Bladder capacity should be estimated prior to performing urodynamics, particularly in children (28). Compliance is a measure of the change in pressure as the volume changes, which is expressed by the equation C ¼ DV/DPdet. Normal bladders have a high compliance; in other words, they allow storage of a large volume of fluid with minimal changes in pressure. Lowcompliance bladders, in contrast, register large changes in Pdet over small changes in volume. The expression of a ratio does not give an accurate picture of the change over time, and other methods such as calculating the slope of the compliance curve or integrating the area under the curve have been proposed as more methodical means of making the calculation (29). In practice, most clinicians look at the slope of the detrusor pressure curve during filling (flat vs. steep) without making formal calculations. Figure 1 demonstrates a study of a patient with low bladder compliance which was improved with treatment. Low compliance is a marker of disease, and it prognosticates deterioration of upper tract morphology and diminished renal function (30,31).



Figure 1 This study demonstrates changes in compliance. A 60-year-old female with a history of a radical hysterectomy and radiation for cervical cancer presented to the hospital with bilateral hydronephrosis and elevated creatinine. A Foley catheter was placed. Her creatinine returned to baseline values, and the hydronephrosis resolved. (A) Abnormal compliance. She was placed on ditropan, imipramine, and intermittent self-catheterization. (B) The study done 2 months later; the abnormal compliance has resolved.

Leak point pressures are another important variable in the CMG. There are two leak point pressures of clinical significance: detrusor leak point pressure (DLPP), and abdominal leak point pressure (ALPP). DLPP is the measure of Pdet required to induce leakage across the urethra when the bladder is the main expulsive force, and it is an important measurement in patients with neurogenic bladders. ALPP, in contrast, measures the resistance of the urethra to short increases in Pabd induced by cough or Valsalva maneuvers. DLPP is an important prognosticator of kidney function. Studies conducted on myelodysplastic children correlated DLPP with the probability of upper tract damage. It was shown that patients with DLPP . 40 cmH2O will develop upper tract damage (5,7,31). Thus, compliance is an important factor, but outlet resistance also contributes to safe bladder function.


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An abnormally compliant bladder that leaks at low pressures is not a dangerous bladder. Conversely, in patients with poor compliance but high outlet resistance, damage will occur (5,32). Figure 2 illustrates two examples of patients with neurogenic bladders and different detrusor leak point pressures. Children who are maintained at low bladder pressures do not develop upper tract damage, but they may not be continent. Efforts to lower outlet resistance will

Figure 2 These examples compare patients with abnormal compliance and different outlet resistance. (A, B) A 61-year-old male with a T4 spinal cord injury (SCI) who underwent an ileal loop 38 years prior to this imaging who sought an undiversion. (A) The image obtained on fluoroscopy. Note the small bladder size and the open bladder neck. (B) Shows the tracing, which demonstrates a low capacity bladder and markedly abnormal compliance. His DLPP is 43 cmH2O. In contrast, (C) shows a 46-year-old with a T12 SCI (Asia D) who presented to a urologist complaining of leakage of urine. Initial urodynamics revealed ISD felt to be of neurological origin. The patient was treated with an artificial urinary sphincter (AUS), and the reservoir is visible. He subsequently complained of persistent leakage, and this urodynamics study shows a low volume, poorly compliant bladder with a high DLPP. (D) The tracing.



Figure 2 Continued.

result in an improvement in compliance in this neurogenic population (33). These clinical discoveries are corroborated by laboratory investigations documenting the effects of hydrostatic pressure in bladder smooth muscle cells (34). Treatments in the neurogenic population should be aimed at lowering DLPP by increasing capacity, improving compliance, and lowering outlet resistance. ALPP is the leak point pressure that measures resistance of the urethra to short increases in abdominal pressure induced by cough or Valsalva maneuvers. This is the more important variable in the patient complaining of leakage who does not have underlying neurological disease. The standardized measurement is obtained by filling the bladder at a medium fill rate to 200 cc. The transducer is placed at a level even with the symphysis, and the patient is asked to


Gruenenfelder and McGuire

strain or cough repetitively until leakage is induced (33). ALPPs ,65 cmH2O are indicative of intrinsic sphincter deficiency. Leakage at pressures 100– 150 cmH2O is more characteristic of urethral hypermobility, although it helps to verify this with videourodynamics (33). Figure 3 demonstrates each of these conditions. These variables are less helpful in the presence of genital prolapse, which tends to dissipate the pressure (35). ALPP is also useful to determine the etiology of postprostatectomy incontinence (16). Figure 4 shows patients with incontinence following treatment for prostate cancer. During the course of filling short increases in Pves that may or may not be associated with leakage are evidence of detrusor instability, also called detrusor hyperreflexia in patients with known neurological diagnoses. Figure 5 illustrates this condition. Detrusor instability is the urodynamic manifestation of urge incontinence, although many patients with urge incontinence will not have urodynamic evidence of detrusor instability (36 – 38). Urge and stress incontinence cannot be reliably distinguished by history and physical alone (8,39). Patients with a history of urge incontinence with demonstrable detrusor instability are said to have motor urge incontinence. If patients are symptomatic but have no evidence of bladder contraction on the CMG, they are said to have sensory urgency (36). The patient is asked to void when he feels full. Voiding pressure is measured, and the flow is recorded in cc/sec. Qmax denotes the highest flow rate recorded in the study. The normal values for men and women are 20 –25 cc/sec and 25 –30 cc/sec, respectively. Because bladder pressure and abdominal pressure can be measured simultaneously, it is

Figure 3 These are two examples of the uses of ALPP. (A) Study of a 47-year-old female who complains of incontinence. The photograph depicts urethral hypermobility and a cystocele. (B) The tracing, and she does not leak until she reaches a pressure of 144 cmH2O during a cough. In contrast, (C) shows the videourodynamics of a 55-year-old female who had a bladder suspension 6 years prior subsequently treated with collagen and carbon particle injections. This photograph illustrates intrinsic sphincter deficiency. She has an open bladder neck at rest. The carbon particles can still be seen lateral to the urethra. (D) The tracing; and Pves is 39 cmH2O when she leaks.



Figure 3 Continued.

possible to differentiate patients with poor flow caused by bladder outlet obstruction from patients with poor flow caused by poorly contracting bladders. Free flow studies and symptomatology are not as reliable measures of BOO. Figure 6 illustrates the urodynamics of a patient with bladder outlet obstruction (BOO). The most widely used measurement of BOO is the Abrams-Griffiths nomogram, which plots maximal flow rate against detrusor pressure at the time of flow. The resulting plot can divide patients into obstructed, nonobstructed, and equivocal (40). Nomograms for obstruction in women have been published but are not as widely used or as well validated (41). This discrepancy reflects that women have fewer


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Figure 3 Continued.

pathological conditions that cause obstruction, and indeed prior anti-incontinence surgery is now the leading cause (42). The electromyogram (EMG) is recorded during the filling and voiding phases of the urodynamics procedure. This is a measurement of depolarization of the sphincter muscle membrane. It can be recorded using either needle electrodes or surface electrodes (anal plug, vagin*l, catheter mounted, or skin patch). The needle electrode perhaps gives more accurate measurements as it can measure individual motor units; however, needle electrodes are considerably more uncomfortable for the patient. A baseline measurement of spontaneous potentials should be recorded. The patient should then be asked to contract the perineal muscles to record maximal firing potential. EMGs can be used to measure integrity of perineal innervation, but they are more commonly used to measure the coordination of voiding (43). The first phase of voiding should be cessation of the electrical activity of the sphincter. If the EMG shows an increase in perineal muscle activity at the onset of voiding, the patient is diagnosed with DESD. These patients are at an increased risk of upper-tract damage from high voiding pressures (44). Figure 7 illustrates the typical videourodynamics appearance of DESD. Learned voiding dysfunction (nonneurogenic neurogenic bladder, or Hinman’s syndrome) is diagnosed when this pattern is seen in a patient with no other neurological findings (45 –47). DESD patients historically were treated with sphincterotomy, but it has been shown that they have similar outcomes when treated with intermittent selfcatheterization (ISC) for management of their bladder dysfunction (44). More recently, urodynamic data following sphincterotomy revealed that these patients often have incomplete surgeries resulting in persistently elevated bladder pressures, and these elevations can cause upper-tract damage (48). Patients with learned voiding dysfunction can be treated with ISC or bladder retraining combined with medications (49).



Videourodynamics improves upon the information obtained from a CMG with the addition of fluoroscopy. The bladder is filled with contrast dye during the CMG, and thus information about



Figure 4 These are two examples of incontinence following a radical prostatectomy. (A) The first has the typical open bladder neck of postprostatectomy incontinence, and his leak point pressure is 39 cmH2O. (B) The second patient has the typical open bladder neck, but a much higher pressure was reached before he leaked. The image shows that he had a urethral stricture that needed to be treated prior to treatment of his incontinence from the prostatectomy.


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Figure 5 This is the study of a 37-year-old female recently diagnosed with multiple sclerosis who complains of urge incontinence and difficulty voiding. (A) Her bladder during filling. The wire above her bladder in this photograph is a nerve stimulator. The bladder neck opens slightly with each contraction. (B) The typical tracing of detrusor hyperreflexia.

structure and function can be gleaned during the test. It is important prior to the initiation of the study, which is more expensive than conventional CMG, to determine if this imaging will yield additional information. It does have the advantage of minimizing some of the artifacts of conventional CMG. Anatomic images can be captured on videotape and correlated specifically with the CMG during filling and voiding. The addition of video is most useful for the assessment of incontinence, neurogenic bladder, and bladder outlet obstruction. It can also be used in preparation for reconstructive procedures and to assess reservoirs or augmented bladders. We



Figure 6 This 60-year-old male with atrial fibrillation and diabetes presented in urinary retention. Physical exam revealed a large prostate estimated at 110 g by subsequent ultrasound. Because of the possibility of diabetic cystopathy causing his retention, urodynamics was performed. (A) A trabeculated bladder with several diverticula. (B) A maximum pressure of 191 cmH2O when the patient attempted to void, although no urine flowed from his bladder. He was subsequently treated with an open prostatectomy, and he now voids to completion.


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Figure 7 This 57-year-old male with multiple sclerosis presented with an inability to void. In this photograph of the voiding phase, his bladder neck is open, but the contraction of the external sphincter keeps the urine from passing through the urethra. He has a trabeculated bladder. Voiding pressure is high.

further use videourodynamics to assess ureters prior to reconstruction. What follows is a description of the methods and uses of videourodynamics.


Equipment and Technique

The typical videourodynamics unit consists of a fluoroscopic unit, a television monitor with videotape capabilities, a multichannel recorder, a system for filling the bladder, and transducers. Almost any type of fluoroscopy unit can be used, and generally the patient is exposed to less than a minute of fluoroscopy. Although we have a dedicated fluoroscopic unit in our clinic, the same information could be obtained from bringing standard CMG equipment to the fluoroscopy suite of any hospital. We favor a triple lumen 10F catheter. The most distal port is the largest, and it is used for infusion of contrast. The next most distal port measures the intravesical pressure, and the third port measures the pressure at the uretha. The catheter position is checked by fluoroscopy and verified when the port measuring urethral pressure gives a pressure tracing that is not identical to the bladder pressure measurements. We then infuse at a fill rate of 50 cc/min. We do not routinely use a rectal balloon to monitor rectal pressure. We feel that the addition of this measurement is not helpful. It adds to the stress of the overall test. Rectal pressure measurements have been advocated as a way of separating increases in abdominal pressure from detrusor instability, but we feel that the same information can be obtained from watching the urethral pressure measurements, which are continuous, and from noting if the bladder neck opens or remains closed and if there is leakage during increases in vesical pressure. It has also been argued that the use of a rectal catheter allows the clinician to distinguish between obstructed and unobstructed flow. We feel that the combination of flow rate, the appearance of



the bladder neck on video, and the measurement of total pressure is sufficient to make that diagnosis, as flow characteristics are determined more by urethral resistance than by the source of pressure, whether it is abdominal straining or elevated detrusor pressure. Similarly, we do not perform EMG during videourodynamics. It is most useful in the diagnosis of DESD, but we feel that the appearance of DESD on video combined with the expected elevations of vesical pressure are sufficient to make this diagnosis. B.

Stress Incontinence

Stress incontinence is a diagnosis clearly aided by the use of videourodynamics. The classification of incontinence historically relied upon radiographic findings (50,51). Stress urinary incontinence is currently defined as type 1, 2, or 3, depending on the presence or absence and degree of urethral and bladder descent (52). Figures 8 –11 illustrate each of these types of incontinence. Figure 12 illustrates how videourodynamics may help clarify the type of leakage in an incontinent patient. Fluoroscopy allows for better visualization of a hypermobile urethra during strain compared to physical exam alone. Patients with significant cystocele and uterine descensus may have falsely elevated ALPP, which makes a diagnosis of the type of incontinence by CMG alone more difficult. Reduction of the prolapse manually or with a pessary is helpful to obtain a more accurate diagnosis, and this is helpful in planning treatment (35). Lack of stress incontinence symptoms in patients with cystoceles is an unreliable indicator of what their voiding may be like after surgical repair of the cystocele. It is therefore helpful to characterize their anatomy with videourodynamics (53). At this point it is unclear what percentage of patients with no symptoms of stress incontinence will be symptomatic following a repair of the prolapse, and it is also unclear if performing the videourodynamics with a pessary helps predict that population. The CARE study is addressing that question, and it is hoped that they will have some early data by 2004. C.

Vesicoureteral Reflux

Videourodynamics is useful for the determination of vesicoureteral reflux. This has several implications. The first is in the treatment of children with vesicoureteral reflux and no underlying neuropathy. Dysfunctional voiding has been implicated both as a cause of vesicoureteral reflux and a reason that surgery fails to correct it (54). Prospective videourodynamic studies have shown that patients with bladder instability and reflux managed nonoperatively with anticholinergics do as well as patients who are treated surgically (14). Thus, determination of the cause of reflux is important in deciding upon a course of therapy. The second use is in patients with neurogenic bladders. The presence of reflux has been shown to alter the reliability of the CMG in examining compliance and capacity (13), which clearly influences treatment decisions. Figure 13 shows an example of a patient with a neurogenic bladder and reflux. The elimination of reflux in patients being treated to alter their capacity and compliance has been shown to be a reliable marker of improvement (55,56). D.

Ureteral Obstruction

Videourodynamics can also be helpful in the measurement of ureteral obstruction. When a patient presents with hydronephrosis, it must be ascertained if the collecting system is merely dilated or truly obstructed. Diuresis scintigraphy and the Whitaker test are the two commonest methods of answering this question. The Whitaker test is performed by through a percutaneous nephrostomy tube. A pressure transducer is placed in the percutaneous nephrostomy tube and in


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Figure 8 This is an example of type 1 incontinence. (A) The vesical neck closed at rest. (B) The descent, not more than 2 cm, during stress. She had an ALPP of 125 cmH2O.

the bladder. The renal pelvis is then infused at a rate of 10 cc/min. The difference in pressure between the bladder and the renal pelvis is calculated. If the difference in pressure is ,13 cmH2O, the system is considered normal. Higher values are consistent with obstruction, and some investigators differentiate mild, moderate, and severe obstruction based on those values (57). Although diuresis scintigraphy has the advantage of being less invasive and is thus



Figure 9 This figure demonstrates type 2A stress incontinence. (A) The bladder at rest, with the vesical neck closed and above the inferior margin of the pubic symphysis. (B) During stress the vesical neck and proximal urethra open and descend .2 cm.


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Figure 10 This patient illustrates type 2B incontinence. (A) A vesical neck closed at rest but located below the margin of the pubic symphysis. (B) When she coughs or Valsalvas, there is significant descent, although there does not have to be any descent be classified as type 2B. Pves was 91 cmH2O when she leaked.



Figure 11 This is an examples of type 3 incontinence or intrinsic sphincter deficiency. (A) The bladder neck open at rest. (B) Leakage during at a leak point pressure ,45 cmH2O.

the preferred first test (58 –61), the Whitaker test offers the advantage of imaging the anatomic point of obstruction when done with fluoroscopy in addition to giving functional information about the kidney. Figure 14 illustrates the use of the test. It has also been observed that positional changes can influence the results of the Whitaker test. Because such positional variations may be relevant clinically, it is important to consider the Whitaker test in diagnosis for patients with abnormal anatomy or intermittent symptoms (62).


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Figure 12 A 49-year-old female underwent a total vagin*l hysterectomy 2 months prior to this study. She complained of incontinence. Fluoroscopy revealed extravasation of contrast into the vagin* consistent with a vesicovagin*l fistula. The patient had normal compliance and no evidence of urethral hypermobility or leakage.

Figure 13 This is the bladder of a 22-year-old patient with myelodysplasia who had a small capacity, trabeculated bladder with poor compliance, reflux, and an open bladder neck at rest. Although the initiation of anticholinergic therapy corrected the compliance and the reflux, she subsequently required a pubovagin*l sling for her intrinsic sphincter deficiency.



Figure 14 (A) The Whitaker test of a 17-year-old male who presented initially with a ureteropelvic junction obstruction diagnosed after a CT was done for abdominal trauma. He was treated with a ureterocalicostomy. His hydronephrosis did not improve. Contrast 50 cc was instilled through his percutaneous nephrostomy tube. Neither the bladder pressure nor the renal pelvis pressure exceeded 10 cmH2O. (B) The Whitaker test of a 34-year-old female patient with myelodysplasia treated initially with a vesicostomy at birth, followed by an ileal loop at puberty. She subsequently had an undiversion with a neobladder and an AUS. She was referred because of bilateral hydronephrosis, and her renal scan was inconclusive. Whitaker test showed rapid appearance of contrast in the bladder; the highest pressure difference between the bladder and the renal pelvis was 2 cmH2O.


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Figure 15 (A) Study of a 68-year-old female who complained of leakage from her stoma following a cystectomy with Indiana pouch. Fluoroscopic urodynamics showed that her compliance is normal, but she has phasic contraction of the bowel segments, during which time she leaked. (B, C) Fluoroscopy images of a 57-year-old male with a neobladder who presented in urinary retention. Videourodynamics revealed bilateral reflux, high voiding pressures, and a stricture at the anastamotic ring.


Figure 15




Urinary Diversions

Videourodynamics is useful in the evaluation of patients who have had urinary diversions for malignancy and for neurogenic bladders. Ileal conduits are the most common incontinent urinary diversions. It is not unusual to have bilateral hydronephrosis following this procedure, but the etiology of the dilatation needs to be elucidated. Patients with refluxing ureteral anastamoses may get chronic dilatation of the urinary tract, but hydronephrosis may also arise from stomal stenosis, ureteroileal anastamosis, or a poorly compliant loop. Knapp et al. used urodynamics to study patients with ileal loops and bilateral hydronephrosis compared to patients with normal upper tracts and ileal loops, and they found significant differences in these patient groups (63). Urodynamics is also helpful in patients with neobladders performed for diversions in patients with bladder cancer or neurogenic bladder. It has been used as an investigative tool to compare the methods of bladder substitution. Lin et al. (64) compared patients with gastric neobladders to patients with small-bowel or ileocecal substitution. They found greater incontinence with lower capacity and worse compliance in the gastric neobladders. Thus, we see that the use of videourodynamics offers a means of comparing new procedures to accepted standards of care for urinary diversion. Santucci (59) compared orthotopic neobladders to stomal urinary reservoirs with urodynamics, and this type of comparative analysis is certainly useful in the preoperative counseling of patients. Videourodynamics also allows for the post operative assessment of patients who complain of incontinence or enuresis following diversion, as illustrated in Figure 15. Ordorica (60) investigated patients with continent colonic urinary reservoirs. Urodynamics allowed the diagnosis of incompetent outlet or high-pressure intestinal contraction of the reservoir as treatable causes of intractable incontinence and showed the causes of difficult catheterization (66,67). El Bahnasawy (62) showed that enuretic patient with orthotopic neobladders had higher


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pressure and postvoid residuals and lower maximum flow and compliance in patients with incontinence (68). Porru and Usai similarly used urodynamics to evaluate incontinence in their neobladder patients (69,70). Similarly, videourodynamics enables monitoring of patients with ileovesicostomy to show that the reservoirs continue to leak at low pressures that are safe for the upper tracts (71 –73). These studies show that videourodynamics is essential in the diagnosis of the incontinent or enuretic patient following urinary diversion.



Videourodynamics combines the functional information obtained with the CMG and flow studies with the anatomical information that can only be obtained using fluoroscopy. The use of urodynamics is clearly essential in the diagnosis and long-term follow-up of patients who have neurogenic bladders. It is also important in the treatment of patients who present with incontinence either initially or as the consequence of another surgical procedure. A primer of urodynamics is beyond the scope of this chapter, but we have attempted to show some of the uses of this valuable tool.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Kaplan SA, Chancellor MB, Blaivas JG. Bladder and sphincter behavior in patients with spinal cord lesions. J Urol 1991; 146(1):113 –117. Watanabe T. High incidence of occult neurogenic bladder dysfunction in neurologically intact patients with thoracolumbar spinal injuries. J Urol 1998; 159(3):965– 968. Kim YH. The correlation of urodynamic findings with cranial magnetic resonance imaging findings in multiple sclerosis. J Urol 1998; 159(3):972– 976. Ciancio SJ. Urodynamic pattern changes in multiple sclerosis. Urology 2001; 57(2):239– 245. McGuire EJ. Prognostic value of urodynamic testing in myelodysplastic patients. J Urol 1981; 126(2):205– 209. Amundsen C. Do urinary symptoms correlate with urodynamic findings? J Urol 1999; 161(6):1871– 1874. McGuire EJ, Cespedes RD. Proper diagnosis: a must before surgery for stress incontinence. J Endourol 1996; 10(3):201 –205. McGuire EJ. The role of urodynamic investigation in the assessment of benign prostatic hypertrophy. J Urol 1992; 148(4):1133– 1136. Abrams P. Objective evaluation of bladder outlet obstruction. Br J Urol 1995; 76(suppl 1):11– 15. Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol 1995; 153(2):342– 344. Bomalaski MD, Bloom DA. Urodynamics and massive vesicoureteral reflux. J Urol 1997; 158(3 Pt 2):1236– 1238. Willemsen J, Nijman RJ. Vesicoureteral reflux and videourodynamic studies: results of a prospective study. Urology 2000; 55(6):939– 943. Morgan JL, O’Connell HE, McGuire EJ. Is intrinsic sphincter deficiency a complication of simple hysterectomy? J Urol 2000; 164(3 Pt 1):767 – 769. Gudziak MR, McGuire EJ, Gormley EA. Urodynamic assessment of urethral sphincter function in post-prostatectomy incontinence. J Urol 1996; 156(3):1131– 1134; discussion 1134– 1135. McGuire EJ. Urodynamic evaluation after abdominal-perineal resection and lumbar intervertebral disk herniation. Urology 1975; 6(1):63 – 70. Cespedes RD. Long-term followup of incontinence and obstruction after salvage cryosurgical ablation of the prostate: results in 143 patients. J Urol 1997; 157(1):237 –240.

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Belville WD. Fiberoptic microtransducer pressure technology: urodynamic implications. Neurourol Urodyn 1993; 12(2):171– 178. Woodside JR, McGuire EJ. A simple inexpensive urodynamic catheter. J Urol 1979; 122(6):788– 789. Woodside JR, McGuire EJ. Clinical evaluation of new urodynamic catheter. Urology 1985; 26(1):95 – 96. Watanabe T, Rivas DA, Chancellor MB. Urodynamics of spinal cord injury. Urol Clin North Am 1996; 23(3):459– 473. Chancellor MB, Blaivas JG. Diagnostic evaluation of incontinence in patients with neurological disorders. Comp Ther 1991; 17(2):37 – 43. Chancellor MB, Kiilholma P. Urodynamic evaluation of patients following spinal cord injury. Semin Urol 1992; 10(2):83 – 94. Wyndaele JJ. The normal pattern of perception of bladder filling during cystometry studied in 38 young healthy volunteers. J Urol 1998; 160(2):479– 481. Wyndaele JJ. Studies of bladder sensitivity in patients with myelodysplasia. Paraplegia 1992; 30(5):333– 335. Zoubek J. The late occurrence of urinary tract damage in patients successfully treated by radiotherapy for cervical carcinoma. J Urol 1989; 141(6):1347– 1349. Kaefer M. Estimating normal bladder capacity in children. J Urol 1997; 158(6):2261 – 2264. Dmochowski R. Cystometry. Urol Clin North Am 1996; 23(2):243– 252. Ghoniem GM. Bladder compliance in meningomyelocele children. J Urol 1989; 141(6):1404– 1406. Ghoniem GM. The value of leak pressure and bladder compliance in the urodynamic evaluation of meningomyelocele patients. J Urol 1990; 144(6):1440– 1442. McGuire EJ, Woodside JR, Borden TA. Upper urinary tract deterioration in patients with myelodysplasia and detrusor hypertonia: a followup study. J Urol 1983; 129(4):823– 826. McGuire EJ, Cespedes RD, O’Connell HE. Leak-point pressures. Urol Clin North Am 1996; 23(2):253– 262. Haberstroh KM. The effects of sustained hydrostatic pressure on select bladder smooth muscle cell functions. J Urol 1999; 162(6):2114 –2118. Romanzi LJ, Chaikin DC, Blaivas JG. The effect of genital prolapse on voiding. J Urol 1999; 161(2):581– 586. Swami SK, Abrams P. Urge incontinence. Urol Clin North Am 1996; 23(3):417 –425. James M. Pure stress leakage symptomatology: is it safe to discount detrusor instability? Br J Obstet Gynaecol 1999; 106(12):1255– 1258. Lim CS, Abrams P. The Abrams-Griffiths nomogram. World J Urol 1995; 13(1):34 – 39. Blaivas JG, Groutz A. Bladder outlet obstruction nomogram for women with lower urinary tract symptomatology. Neurourol Urodyn 2000; 19(5):553– 564. Groutz A, Blaivas JG, Chaikin DC. Bladder outlet obstruction in women: definition and characteristics. Neurourol Urodyn 2000; 19(3):213– 220. Siroky MB. Electromyography of the perineal floor. Urol Clin North Am 1996; 23(2):299– 307. Groutz A. Learned voiding dysfunction (non-neurogenic, neurogenic bladder) among adults. Neurourol Urodyn 2001; 20(3):259– 268. Phillips E, Uehling DT. Hinman syndrome: a vicious cycle. Urology 1993; 42(3):317– 319; discussion 319– 320. Hinman F Jr. Nonneurogenic neurogenic bladder (the Hinman syndrome)—15 years later. J Urol 1986; 136(4):769– 777. McGuire EJ, Brady S. Detrusor-sphincter dyssynergia. J Urol 1979; 121(6):774– 777. Kim YH, Kattan MW, Boone TB. Bladder leak point ressure: the measure for sphincterotomy success in spinal cord injured patients with external detrusor-sphincter dyssynergia. J Urol 1998; 159(2):493– 496; discussion 496– 497. Allen TD. The non-neurogenic neurogenic bladder. J Urol 1977; 117(2):232– 238. Blaivas JG, Olsson CA. Stress incontinence: classification and surgical approach. J Urol 1988; 139(4):727– 731.

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Gruenenfelder and McGuire Gardy M. Stress incontinence and cystoceles. J Urol 1991; 145(6):1211– 1213. Greenfield SP, Wan J. The relationship between dysfunctional voiding and congenital vesicoureteral reflux. Curr Opin Urol 2000; 10(6):607– 610. Agarwal SK. Urodynamic correlates of resolution of reflux in meningomyelocele patients. J Urol 1997; 158(2):580– 582. Flood HD. Outcome of reflux in children with myelodysplasia managed by bladder pressure monitoring. J Urol 1994; 152(5 Pt 1):1574 –1577. Pfister RC, Papanicolaou N, Yoder IC. Diagnostic morphologic and urodynamic antegrade pyelography. Radiol Clin North Am 1986; 24(4):561– 571. Lupton EW. A comparison of diuresis renography, the Whitaker test and renal pelvic morphology in idiopathic hydronephrosis. Br J Urol 1985; 57(2):119– 123. Hay AM. A comparison between diuresis renography and the Whitaker test in 64 kidneys. Br J Urol 1984; 56(6):561– 564. Senac MO Jr, Miller JH, Stanley P. Evaluation of obstructive uropathy in children: radionuclide renography vs. the Whitaker test. AJR 1984; 143(1):11– 15. Jakobsen H. Sensitivity of 131I-hippuran diuresis renography and pressure flow study (Whitaker test) in upper urinary tract obstruction. Urol Int 1988; 43(2):89 – 92. Ellis JH. Positional variation in the Whitaker test. Radiology 1995; 197(1):253– 255. Knapp PM Jr. Urodynamic evaluation of ileal conduit function. J Urol 1987; 137(5):929 –932. Lin DW. Urodynamic evaluation and long-term results of the orthotopic gastric neobladder in men. J Urol 2000; 164(2):356– 359. Santucci RA. Continence and urodynamic parameters of continent urinary reservoirs: comparison of gastric, ileal, ileocolic, right colon, and sigmoid segments. Urology 1999; 54(2):252– 257. Ordorica RC. Evaluation and management of mechanical dysfunction in continent colonic urinary reservoirs. J Urol 2000; 163(6):1679– 1684. Masel JL. Evaluation of flap valve as an alternative continence mechanism in the Florida pouch. Urology 1999; 53(3):506 –509. El Bahnasawy MS. Nocturnal enuresis in men with an orthotopic ileal reservoir: urodynamic evaluation. J Urol 2000; 164(1):10– 13. Porru D. Behaviour and urodynamic properties of orthotopic ileal bladder substitute after radical cystectomy. Urol Int 1994; 53(1):30 – 33. Porru D, Usai E. Orthotopic ileal bladder substitute after radical cystectomy: urodynamic features. Neurourol Urodyn 1994; 13(3):255– 260. Rivas DA, Karasick S, Chancellor MB. Cutaneous ileocystostomy (a bladder chimney) for the treatment of severe neurogenic vesical dysfunction. Paraplegia 1995; 33(9):530– 535. Mutchnik SE. Ileovesicostomy as an alternative form of bladder management in tetraplegic patients. Urology 1997; 49(3):353 –357. Leng WW. Long-term outcome of incontinent ileovesicostomy management of severe lower urinary tract dysfunction. J Urol 1999; 161(6):1803– 1806.

12 Pharmacologic and Surgical Management of Detrusor Instability H. Henry Lai, Michael Gross, Timothy B. Boone, and Rodney A. Appell Baylor College of Medicine, Houston, Texas, U.S.A.



Overactive bladder (OAB) is characterized by the urinary symptoms of frequency, urgency, and urge incontinence as a result of involuntary detrusor contractions during bladder filling. Such contractions are predominantly under the control of the parasympathetic nervous system. Acetylcholine released from the parasympathetic nerve endings activates the M3 muscarinic receptors on the detrusor smooth muscles and modulates bladder contractility. Antimuscarinic agents inhibit the binding of acetylcholine to the muscarinic receptors and suppress involuntary detrusor contraction (1). Immediate-release oxybutynin was the gold standard in pharmacologic treatment of OAB for almost three decades. Its antimuscarinic (M3) activity is nonselective for the urinary bladder, resulting in significant systemic side effects, particularly dry mouth, that limit its clinical utility (2,3). Even though alternative routes of administration of oxybutynin, such as intravesical instillation (4 – 6), intravesical implant (7), and rectal suppository (8), are available, oral agents remain the mainstay in treatment of OAB. Newer pharmacologic agents, e.g., tolterodine, and modified drug delivery mechanisms for oxybutynin (e.g., extended-release oxybutynin) have revolutionized the treatment of OAB (4,5). New drugs are always compared not only to placebo but also to immediate-release oxybutynin, because of its long history and established efficacy (6). Originally identified in the 1960s as a potential treatment for gastrointestinal hypermobility, oxybutynin was found to be effective in inhibiting involuntary bladder contractions. It is a receptor subtype – specific antagonist that binds with higher affinity to the M3 muscarinic receptors than to the other receptor subtypes (M1, M2, M4, and M5). Oxybutynin also has direct spasmolytic (musculotropic) and local anesthetic effects on the detrusor. Even though the clinical efficacy of immediate-release oxybutynin is well documented, dose-related antimuscarinic side effects are frequent. Dry mouth is the most common and bothersome complaint, followed by constipation, blurred vision, dry eyes, urinary retention, and drowsiness. These systemic side effects occur because oxybutynin is not targeted specifically to the lower urinary tract. It also inhibits M3 receptors in the salivary glands, which mediate salivary secretion, and M3 receptors in the intestines, which regulate bowel peristalsis. Clinically, immediate-release oxybutynin appears more potent in causing dry mouth than in inhibiting detrusor instability. This adverse effect is often severe enough to cause poor patient 191


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compliance, suboptimal dosing, and even drug discontinuation. Only 18 –22% of patients treated with immediate-release oxybutynin remained on the medication after 6 months due to intolerable side effects (9,10). Since OAB is a chronic debilitating condition requiring long-term treatment, it is important that pharmacologic therapy be not only effective but also well tolerated. The challenge has been to develop antimuscarinic agents that are as effective as immediate-release oxybutynin but without the side effect loads.



Tolterodine (Detrol) was the first drug developed specifically for the treatment of OAB. It is a competitive muscarinic antagonist that exhibits similar affinities for muscarinic receptor subtypes M1 –M5. Unlike immediate-release oxybutynin, which is a receptor subtype – specific agent (for M3), tolterodine may be a more target-specific drug that possesses stronger selectivity for the urinary bladder than for the salivary glands. In an anesthetized cat model (but only six cats), tolterodine appeared more potent in inhibiting detrusor instability than salivation. This is in contrast to immediate-release oxybutynin, which exhibited the opposite tissue-selective profile (11,12). In a pilot study with healthy volunteers, tolterodine was well tolerated and exhibited greater objective and subjective antimuscarinic effects on detrusor function than on salivation (13). However, in another study on the effects on salivary volume, at 2 h following tolterodine (2 mg) or immediate-release oxybutynin in healthy volunteers, there was less suppression of salivary volume with immediate-release oxybutynin. However, there was a complete return to normal by 10 h in the volunteers taking tolterodine, and those taking immediate-release oxybutynin took longer to regain their respective salivary volume. In addition, another group taking extended-release oxybutynin (10 mg) had a constant salivary volume that was only slightly below that of those who were given placebo (14). The precise mechanism responsible for any bladder-selective property of tolterodine remains to be elucidated. Whether this is related to the differential affinities of the muscarinic receptors in salivary glands and those in detrusor muscles for tolterodine and for immediate-release oxybutynin or its metabolites remains to be confirmed in the human (4). The recommended dosage of tolterodine is 2 mg BID based on Phase II dose-ranging studies. No dose adjustment is necessary on the basis of metabolic phenotype (cytochrome P450 “extensive” vs. “poor” metabolizers) (15). Obviously, as the dosage of tolterodine increases, clinical response improves, but tolerability declines. At a dosage of 2 mg BID, the incidence of adverse effects, including dry mouth, is similar to that found with placebo, but clinical efficacy is comparable to that of immediate-release oxybutynin. A lower dose (1 mg BID) results in less favorable improvements in maximum cystometric capacity and volume at first contraction in urodynamic tests. A higher dose (4 mg BID) quadruples postvoid residual volume (from 48 mL to 163 mL) and may increase the risk of urinary retention (15,16). The rate of dry mouth also approaches 56% at the higher dose (12). Ultimately, the recommended dosage of tolterodine was set at 2 mg BID with the aim of achieving efficacy similar to that of immediate-release oxybutynin but without the same side-effect burden. The half-life of tolterodine is 4 h. Progression to peak therapeutic action is rapid. In Phase I clinical trials with healthy volunteers, tolterodine exerted a marked inhibitory effect on bladder function within 2 h after a single oral dose (13,17). However, clinically noticeable decreases in voiding frequency and incontinence episodes do not occur immediately when behavioral aspects of patients are taken into account. Modification of voiding habits is a gradual process, and it takes a period of time for the patient to trust the enhanced control that he or she begins to experience from the medication. Patients achieve 70% of the maximum effects within 2 weeks of treatment initiation (18,19). Optimal

Management of Detrusor Instability


relief of OAB symptoms is achieved after 8 weeks of treatment (6,18,20). Clinical response is sustained for at least a year in patients who are compliant and continue to take the medication (8). A.

Tolerability of Tolterodine over Immediate-Release Oxybutynin

The tolerability of tolterodine over immediate-release oxybutynin has been demonstrated by numerous Phase III clinical trials. Most of these were prospective, randomized, multicenter, placebo-controlled, parallel-group, double-blind studies that directly compared tolterodine to immediate-release oxybutynin and placebo in patients who had urodynamically confirmed and/ or clinically significant bladder overactivity (18,21,22). Many of these trials were 12 weeks in duration and virtually identical in study design, a feature that permitted data pooling and metaanalysis to include over 1000 patients, increasing statistical power (23,24). Phase III randomized trials have consistently demonstrated comparable objective and subjective efficacy between tolterodine and immediate-release oxybutynin. Tolterodine reduced the micturition frequency by 17 –21%, reduced urge incontinence episodes by 47%, and increased mean volume per micturition (which is a surrogate measurement of bladder capacity) by 21– 27% (18,21). Improvements in voiding diary variables were comparable between patients who were randomized to receive 2 mg BID of tolterodine and those receiving 5 mg TID a day of immediate-release oxybutynin (see Table 1), with the exception that immediaterelease oxybutynin appeared to more effective in relieving urge urinary incontinence than tolterodine in one study 71% vs. 47%, respectively (18). These objective improvements in voiding diary parameters were clinically relevant to the patient, as they translated into subjective improvements in the patient’s perception of bladder symptoms. When asked to rate their symptoms on an analog scale, 52% of tolterodine patients reported an improvement in symptom scores after 12 weeks of treatment, compared with 50% and 39% of patients taking oxybutynin and placebo, respectively (23). Despite comparable efficacy at their recommended doses, tolterodine was better tolerated than immediate-release oxybutynin. Dry mouth was still the most common adverse effect (18,21,23). However, with tolterodine, there was a lower incidence of dry mouth, and, as assessed by patients on an analog scale, there was a lower intensity of dry mouth when it occurred. Half as many patients experienced dry mouth in the tolterodine arm (30 – 50%) as in the oxybutynin group (69 – 87%). Most patients with dry mouth in the tolterodine arm reported it to be mild, whereas most patients in the immediate-release oxybutynin group reported it as moderate or severe (see Table 1). In studies that permitted dose reduction to prevent drug discontinuation, the frequency and intensity of dry mouth remained higher among patients who reduced their oxybutynin dosage from 5 mg TID to 2.5 mg TID (due to adverse effects), compared with those who remained on the regular dose of tolterodine (2 mg BID) (18). Fewer patients in the tolterodine arm withdrew from the study (6 – 8% vs. 17– 21% in the oxybutynin arm) or reduced their dosage (7 – 8% vs. 23 –32% in oxybutynin) as a result of adverse effects (18,21,23). The equivalent clinical efficacy and superior tolerability of tolterodine compared to immediate-release oxybutynin translate into higher patient compliance and fewer treatment withdrawals or dosage reductions. Tolterodine overcomes the current limitations of immediate-release oxybutynin and offers a therapeutic advantage in terms of improved tolerability. There are suggestions that tolterodine improves overall quality of life (QOL) as measured by the Medical Outcomes Study 36 (MOS-36) 36-item short-form (SF-36) instrument of OAB patients to a greater extent than oxybutynin or placebo, even though at this time, no disease-specific QOL tool has been developed for patients with OAB (25). In clinical practice, immediate-release oxybutynin is commonly started at a lower initial dose of 2.5 mg TID and then titrated up to 5 mg TID to achieve a balance between efficacy and


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Table 1 Tolterodine (Detrol) Versus Immediate-Release Oxybutynin Outcome Frequency of micturition Number of urge incontinence episodes Volume per micturition Percent of patients with side effects Percent of patients with dry mouth Percent of patients with moderate to severe dry mouth Percent of patients who withdrew due to side effects Percent of patients who reduced dosage due to side effects



Abrams et al. (18) Drutz et al. (21) Abrams et al. Drutz et al.

221% 217% 247% 246%

219.5% 217% 271% 252%

Abrams et al. Drutz et al.

þ27% þ21%

þ31% þ34%

89% 78% 75% 50% 30% 40% 14% 9% 17%

97% 90% 93% 86% 69% 78% 51% 44% 60%

Abrams et al. Drutz et al. Appell et al.

8% 6% 8%

17% 21% 20%

12% 7% 5%

Abrams et al. Drutz et al. Appell et al.

8% 7% 9%

32% 23% 32%

2% 4% 4%

Abrams et al. Drutz et al. Appell et al. (23) Abrams et al. Drutz et al. Appell et al. Abrams et al. Drutz et al. Appell et al.


Placebo 210.5% 29% 219% 227% þ7% þ8%

Comments Tolterodine and immediaterelease oxybutynin demonstrated comparable efficacy.

81% Tolterodine 75% exhibited 78% tolerability 21% superior to that 15% of immediate40% release (not reported) oxybutynin. (not reported) 6%

tolerability (26 – 28). A study was therefore performed to compare tolterodine with immediaterelease oxybutynin using an upward titration protocol (started at 2.5 mg, then increased to 5 mg TID after 2 weeks) in patients .50 years of age to determine whether tolterodine was better tolerated than immediate-release oxybutynin in that clinical scenario. Not surprisingly, despite the upward titration strategy, tolterodine still exhibited comparable efficacy and superior tolerability to those of immediate-release oxybutynin (20). The long-term tolerability of tolterodine was demonstrated by open-label studies, even though randomized trials that directly compare long-term adverse effects of tolterodine to those of immediate-release oxybutynin are lacking. Only 9% and 15% of tolterodine patients withdrew from open-label studies owing to side effects at 9 months and 12 months, respectively. Another 13% and 23% opted for dose reduction at the end of 9 months and 12 months, respectively (29,30). This is in contrast to immediate-release oxybutynin; only 18% of OAB patients remained on this therapy after 6 months owing to intolerable side effects (2,10). Retrospective analysis of a filled prescription pharmacy database also confirmed that more OAB patients remained on tolterodine therapy than on immediate-release oxybutynin after 6 months of treatment (9). A poor response to oxybutynin in the past does not preclude patients from being able to tolerate long-term treatment with tolterodine. In fact, tolterodine was well tolerated in

Management of Detrusor Instability


89% of patients who had previously found oxybutynin to be unacceptable. There is no evidence that antimuscarinic side effects worsened over time with long-term use (29). B.


When clinical trials of tolterodine first began, there was concern over the cardiac safety of the medication, since it is closely related to terodiline, a drug that was removed from the market in the 1980s because of concerns over arrhythmias and acute cardiac events. In almost every tolterodine study, patients were very closely monitored and evaluated with respect to EKG changes and potential adverse cardiac events. Other than a slight dose-dependent increase in heart rate (3 –12 beats per minute) (15,31,32), and a corresponding shortening in uncorrected QT interval, which one would expect from the antimuscarinic activity of tolterodine, no clinically relevant changes in corrected QT intervals or EKG morphology were apparent (32). No serious adverse cardiac event attributed directly to tolterodine use has been documented in any of more than a few dozen well-conducted clinical trials. Overall, CNS side effects are rare (19,33). Unlike immediate-release oxybutynin and its major metabolite (N-desethyloxybutynin), which cross the blood-brain barrier and theoretically may cause CNS adverse effects such as somnolence and cognitive impairment (34), tolterodine has lower lipophilicity and therefore probably less penetration into the CNS (35,36), but it must be remembered that tertiary amines all pass through the blood-brain barrier and both oxybutynin and tolterodine are tertiary amines. Although tolterodine caused fewer disturbances on quantitative-topographic EEG than oxybutynin in healthy volunteers (37) and the reported incidence of somnolence in patients treated with immediate-release oxybutynin was 11.9%, in patients on tolterodine, it was 3.0% (38). This must be taken in the context that clinical problems have not been demonstrated in patients on extended-release oxybutynin, which may, again, mean that CNS problems, if any, on oxybutynin may relate to metabolites of oxybutynin and not the parent compound. Tolterodine has no deleterious effects on blood pressure or on hematologic or biochemical laboratory values during long-term treatment (29). It is safe and well tolerated in the elderly over 65 years of age (20,39). No cardiac arrhythmias were noted in a study that exclusively recruited patients over 65 years of age (39). Although based on limited numbers of subjects, with short follow-ups, another study found that tolterodine (0.1 mg/kg/d in two divided doses) appeared to be safe in pediatric meningomyelocele patients with detrusor hyperreflexia (40).



An extended-release formulation of oxybutynin (Ditropan XL) was released in 1999 (38). This once-a-day formulation uses a patented oral osmotic (OROS) drug delivery system to slowly release a controlled amount of oxybutynin into the gastrointestinal tract over a 24-h period. Physically, extended-release oxybutynin resembles a conventional tablet, but it consists of two core compartments: a drug layer containing the active ingredient (oxybutynin), and a push layer containing osmotically active compounds. Both are wholly surrounded by a semipermeable membrane with a laser-drilled hole on the drug side. Water in the gastrointestinal tract enters the tablet and mixes with the oxybutynin to form a suspension. Water also enters the push layer through the semipermeable membrane via osmosis. The push layer expands and pushes the suspended drug out of the orifice into the gastrointestinal tract for absorption. Aside from the convenience of once-daily administration, extended-release oxybutynin eliminates the three times daily peak-to-trough serum concentration fluctuation associated with


Lai et al.

immediate-release oxybutynin. Such marked variation in oxybutynin level is thought to contribute to the intolerable dose-dependent side effects of the drug. Studies with adult volunteers have shown a smoother peak-to-trough fluctuation of plasma concentration with each dosing of extendedrelease oxybutynin. Plasma level rises slowly over 4–6 h and remains fairly constant over the 24-h dosing interval (41,42). Steady-state concentration is reached by day 3 of administration. In addition, the peak serum concentration of oxybutynin in the extended-release formulation is 2.5 times lower than that of the conventional formulation (41). Lower peak value and more stable serum concentration are the pharmaco*kinetic hallmarks of extended-release oxybutynin. Oxybutynin is metabolized by the cytochrome P450 enzyme system in the liver and the small intestinal wall (“first-pass” metabolism). The primary metabolite, N-desethyloxybutynin, is largely responsible for systemic side effects, particularly dry mouth and CNS effects (41 –43). There is evidence that although oxybutynin and N-desethyloxybutynin have similar effects on the detrusor, N-desethyloxybutynin is more potent in the salivary glands and causes more severe dry mouth than the parent compound. Immediate-release oxybutynin, like most other oral medications, is absorbed primarily in the small intestine and drains into the portal system. It undergoes extensive first-pass metabolism in the upper gastrointestinal tract, producing high serum levels of N-desethyloxybutynin, which causes intolerable side effects. In contrast, extended-release oxybutynin is protected inside a nondisintegrating OROS capsule. It is released at a steady rate for 24 h, spending only 3 –5 h in the upper gastrointestinal tract. Most of it is released in the colon, where first-pass metabolism is much less extensive than in the small bowel (44,45). As a result, first-pass metabolism is proportionally reduced, the serum ratio of N-desethyloxybutynin to oxybutynin is reduced, and less severe dry mouth may be experienced (42). This hypothesis is supported by a pilot study that showed that mean bioavailability was higher for oxybutynin (153%) and lower for N-desethyloxybutynin (69%) in extended-release oxybutynin than with immediate-release oxybutynin (41). A.

Improved Tolerability over Immediate-Release Oxybutynin

More stable serum concentration together with less first-pass metabolism may explain the improved tolerability of extended-release oxybutynin over immediate-release oxybutynin. Extended-release oxybutynin caused less suppression of saliva output and less severe dry mouth than immediate-release oxybutynin in healthy adult volunteers (41,42). Whereas patients taking extended-release oxybutynin and immediate-release oxybutynin had similar reductions in urge incontinence (83% and 76– 87%, respectively) and total incontinence episodes (80 –81% and 75 –86%, respectively), indicating equivalent clinical efficacy (43,46), the incidence and severity of dry mouth were lower in the extended-release oxybutynin group (see Table 2). Dry mouth of any severity was reported by 68% and 87% of patients in the extended-release oxybutynin and immediate-release oxybutynin groups, respectively (P ¼ .04) (43). Moderate or severe dry mouth occurred in 25% and 46%, respectively (P ¼ .03). Dry mouth was still the most common side effect of the extended-release formulation (68%), followed by somnolence (38%), constipation (30%), and blurred vision (28%). With the exception of dry mouth, extended-release oxybutynin and immediate-release oxybutynin were comparable in terms of the rates of systemic side effects. In one open-label study, 7.8% of OAB patients discontinued extended-release oxybutynin at the end of 12 weeks because of adverse effects (47). Notably, neither the comparative (43,46) nor the open-label studies (47) had a placebo arm, so the extent of placebo effects cannot be ascertained. Whether the more favorable side-effect profile of extended-release oxybutynin translates into higher patient compliance and fewer treatment withdrawals or dosage reductions remains to be studied in placebo-controlled trials. For patients whose bladder symptoms have

Management of Detrusor Instability


Table 2 Extended-Release Oxybutynin Versus Immediate-Release Oxybutynin Outcome


Extended-release oxybutynin

Immediate-release oxybutynin

Number of urge incontinence episodes Percent of patients achieving total continence

Anderson et al.(43)a Versi et al.(46)

284% 283%

288% 276%

Anderson et al.



Anderson et al.



Percent of patients with side effects Percent of patients with dry mouth Percent of patients with moderate to severe dry mouth

Percent of patients who withdrew due to side effects

Anderson et al. Versi et al. Anderson et al. Versi et al.

Anderson et al. Versi et al.

4% 9% 19% 40%

68% 48% 25% (at 5 mg/d) (at 10 mg/d) (at 15 mg/d) (at 20 mg/d) 15% 3%

7% (at 26% (at 39% (at 45% (at

87% 59% 46% 5 mg/d) 10 mg/d) 15 mg/d) 20 mg/d) 13% 6%

Comments Extended-release and immediaterelease oxybutynin demonstrated equivalent efficacy. Extended-release oxybutynin is better tolerated than immediaterelease oxybutynin.


Dosage up to 30 mg/d was allowed in the extended-release randomized arm.

been stabilized on immediate-release oxybutynin, switching to extended-release oxybutynin reduces the side effects without compromising clinical efficacy (48). Maximum clinical benefit is achieved by week 4 and is sustained through 12 weeks of maintenance therapy. The optimal dosage appears to be between 5 and 15 mg daily. In one trial, 70.8% of participants chose a maintenance dose of 5–15 mg, while 17% used a dose of 25–30 mg daily. Although the latter doses are higher than the maximum recommended dose, only 5.4% of these patients discontinued treatment owing to antimuscarinic side effects (47). Up to 30 mg/d of extended-release oxybutynin has been used safely in controlled studies (43). Extended-release oxybutynin may provide important therapeutic options for motivated patients who require a higher dose to achieve optimal relief of OAB symptoms without experiencing excessive side effects (e.g., neurogenic bladder).


Safety and Efficacy in the Elderly

Extended-release oxybutynin appears to be safe in the elderly. In a long-term, open-label, community-based study, there was a very low incidence of CNS side effects, including changes in mental acuity and memory (49). Over 50% of patients in that community-based study were over 65 years of age. The drug demonstrated comparable efficacy across all age groups. In a different open-label study evaluating urge incontinence, nearly equal numbers of patients older and younger than 65 years achieved complete urinary continence (46). In addition, the rates of dry mouth were similar. These results are important, since urge urinary incontinence is not only prevalent among the elderly (affecting 12 –38% over age 60)(50) but is also the second leading cause of patient admissions to nursing homes (51).



Lai et al.

Long-Term Tolerability and Compliance

Historically, only 18 – 22% of patients remained on long-term (.6 months) treatment with immediate-release oxybutynin (9,10), in contrast to the case with extended-release oxybutynin; 60% of patients remained on the latter drug at 12 months, at doses of 15 mg or less (49). Overall QOL is improved with long-term treatment of extended-release oxybutynin, as sleep disturbance is reduced and incontinence impact questionnaire scores are lowered. Of patients taking extended-release oxybutynin, 80% reported that the medication worked well or very well, and 88% were pleased or extremely pleased with the results. Only 16% of patients discontinued therapy owing to adverse effects over the 12-month study period; the majority of these did so by 3 months. One prospective, randomized, double-blind, parallel-controlled study directly compared extended-release oxybutynin (10 mg/d) to tolterodine (2 mg BID) (52). Extended-release oxybutynin appeared to be more effective than tolterodine in reducing voiding frequency (26.9% vs. 21.9%), urge incontinence episodes (76.2% vs. 67.6%), and total incontinence episodes (75.2% vs. 65.6%). The incidence of dry mouth (28.1% with extended-release oxybutynin vs. 33.2% with tolterodine), the severity of dry mouth (moderate to severe: 10.2% vs. 10.9%), and rates of treatment discontinuation due to side effects (7.6% vs. 7.8%) showed no statistically significant difference.



An extended-release, once-daily formulation of tolterodine (Detrol LA) is now available (53). It uses a different extended-release technology from the OROS system. It has been found that gastric pH may affect the bioavailability of the drug and that if extended-release tolterodine is taken with antacids, the drug is released too soon, and the effective time of the medication may be shortened and the tolerability reduced (6). In contrast, the drug metabolism and bioavailability of extended-release oxybutynin are not affected by dietary intake of antacids. Pharmaco*kinetic studies in healthy volunteers suggested that the extended-release formulation of tolterodine has a smoother peak-to-trough concentration profile than immediate-release tolterodine (54). In the largest placebo-controlled study ever conducted in patients with OAB (more than 1500 patients), extended-release tolterodine (4 mg/d) demonstrated efficacy and tolerability superior to those of immediate-release tolterodine (2 mg BID). Both extended-release and immediate-release tolterodine significantly reduced number of incontinence episodes, voiding frequency, and pad use compared to placebo (55). Notably, the extended-release formulation was reported to be 18% more effective than regular tolterodine in reducing the median number of incontinence episodes (P , .05). The physiological explanation for improved efficacy is not clear; the difference may be related to statistical variations induced in the performance of the analysis. For example, when the same statistics are based on the means rather than the median reduction of overactive bladder symptoms, there is no statistical difference between extendedrelease tolterodine (4 mg/d) and immediate-release tolterodine (2 mg BID). The most common adverse effect was dry mouth. Aside from this, all other systemic side effects were seen with similar frequency in the treatment groups and the placebo group. In the extended-release arm, 23% of patients experienced dry mouth, of whom 1.8% reported severity that interfered significantly with patient’s usual functioning (55). Patients taking extendedrelease tolterodine had a 23% lower incidence of dry mouth than those taking regular tolterodine (P , .02), even though the rates of drug withdrawal (5%) were similar between the two groups

Management of Detrusor Instability


at the end of 12 weeks. Extended-release tolterodine was reported to be more effective in reducing urge incontinence and better tolerated than the immediate-release formulation. Head-to-head comparative studies between extended-release tolterodine and extendedrelease oxybutynin are under way but have yet to be published. Both extended-release tolterodine and extended-release oxybutynin offer therapeutic advantages over immediaterelease forms of these drugs, but it remains uncertain if either drug is better than the other in terms of efficacy, tolerability, and compliance.



When medical therapy fails, surgical intervention from electrical stimulation done as an office procedure to extensive procedures like augmentation or urinary diversion may be needed. Any surgical intervention should be tailored to the patient with consideration of the degree of his/her discomfort, underlying pathology, general health, and, obviously, the patient’s own motivation. A.


Hydrodistension for irritative bladder symptoms was introduced in 1930 and was shown to reduce pain, urgency, frequency, and to increase bladder capacity (56,57). The mechanism of action is unclear. It has been suggested that hydrodistension leads to ischemic or mechanical damage to submucosal nerve plexuses and stretch receptors thus leading to attenuation of pain, frequency, and increase in bladder volume (58). This theory has been supported by axonal degeneration seen in animal bladders after hydrodistension (59). Other suggested theories are reduced proliferation rate of urothelial cells, reduced epidermal growth factors, and increased urinary antiproliferative growth factor (59,60). A defect in bladder surface mucin may exist in patients with interstitial cystitis in comparison to controls (61). In vitro and in vivo studies have demonstrated that hydrodistension leads to increased urothelial excretion of substances such as heparin-binding epidermal growth factor and glycoprotein-51 component of bladder surface mucin and decreased excretion of antiproliferative growth factors (62). Even though hydrodistension is a commonly used procedure, the best regimen and the optimal frequency of treatments are still unknown. Two techniques that are used are the simple hydraulic filling and the Helmstein intravesical balloon hydrodistension (63). In most cases hydrodistension is done under regional or general anesthesia. In the simple hydraulic procedure the bladder is filled with either sterile water or saline at 80 cmH2O until filling stops or until there is leakage around the cystoscope. The bladder is drained after a few minutes. Some physicians drain the bladder and refill it two or three times (62). For the Helmstein intravesical balloon hydrodistension, the patient is under regional anesthesia. A catheter with a pressure transducer is inserted into the bladder and the patient is taken to the recovery room. The intravesical pressure is monitored for 3 h, and whenever the pressure goes below the midsystolic diastolic pressure, more saline is applied to the catheter’s balloon. This procedure is especially useful for lowcapacity bladders. Most patients will require repeated procedures. The method of treatment and the definitions of response are not standardized, and the therapeutic efficacy of hydrodistension is therefore difficult to evaluate, but the reported success rates range from 18% to 77%. Complications range from 5% to 10% with hematuria, dysuria, urinary retention, and bladder perforation being the most common (62,64 –66). The degree and duration of relief that will be obtained in a given patient are unpredictable, but in most cases the procedure offers only a temporary relief.



Lai et al.

Ingelman-Sundberg Bladder Denervation Technique

Ingelman-Sunderg reported his transvagin*l peripheral bladder denervation in 1959 (67). In his preliminary series he studied 32 women with detrusor instability, and reported an 88% success rate and a 70% cure rate. The procedure is considered to be most efficacious for patients with detrusor instability. Patients with neurogenic bladders, poor compliance, and interstitial cystitis gain less from the procedure. The assumption is that the procedure causes partial sensory denervation of the trigonal area. The original procedure required extensive dissection of the cervix and the bladder pedicals bilaterally with dissection of terminal pelvic nerve branches. Since then the procedure has been modified with dissection limited to the bladder neck and the subtrigonal area. Use of transvagin*l local anesthesia in order to predict therapeutic outcome has achieved favorable results (68). Transvagin*l local anesthesia may be achieved with 5– 15 cc of 0.25% bupivacaine injected in the undersurface of the trigone. Resolution of symptoms for several hours indicates that the patient may benefit from the procedure. The procedure is performed under local or regional anesthesia. The patient is put in lithotomy position, and a Foley catheter is inserted. The subtrigonal area is infiltrated with normal saline, and an inverted U-shaped incision is made over the anterior vagin*l wall with the apex slightly proximal to the bladder neck. The vagin*l mucosa and the pubocervical fascia are transected off the underlying surface of the bladder. The transection at this level causes partial denervation of the bladder. The vagin*l flap is closed, and a vagin*l pack is left for a few hours. The operation can be performed in 15– 30 min and may be done in an outpatient setting. Other studies that employed the Ingelman-Sundberg technique showed long-term success rates of 50 –72% (69,70). Cespedes et al., selecting patients according to their response to transvagin*l local anesthesia, demonstrated a cure rate of 64% (68). Cure was regarded as complete resolution of urge incontinence (UI). About 70% of these women still required some medications after the procedure. In 34% there was only temporary or no response. The most frequent complication after the procedure was urinary retention that was self-limited.


Transvesical Phenol Injections

Subtrigonal injections of 6% phenol for the treatment of bladder instability were reported in 1969 (71). Injection of these materials causes neurolysis of terminal pelvic nerve branches as they enter the trigone. Approximately 10 – 20 cc of the material is injected through a cystoscope in the submucosal level, bilaterally half-way between the bladder neck and each ureteral orifice. The procedure requires either general or regional anesthesia. This treatment modality has yielded mixed results, with some investigators reporting success rates as high as 82 –90% (72,73) while others report poor success rates of 14 – 19% (74 – 76). Some studies attempted to identify subcategories of patients who were most likely to benefit from this procedure. Blackford et al. reported a success rate of 82% in women over the age of 55 years and ,14% in women younger than that (72). In other studies patients with multiple sclerosis appeared to benefit most from this procedure (72,77). To improve patient selection Madjar et al. used a transvagin*l bupivacaine injection (0.25%) on the assumption that patients who respond to the local anesthetic will later respond to the subtrigonal phenol injection. In their study 23 of 42 patients (54.7%) responded to the bupivacaine injection. Of all the patients who responded to the phenol injections, 26% had symptomatic relief that lasted .3 months. In most cases relief of symptoms is temporary and lasts from a few weeks to several months. Severe complications, such as vesicovagin*l fistulas, excoriation of the vagin*l wall, and even the need for urinary diversion, were reported in 25– 40% in two series (73,78). However, in these patients the phenol was mixed in a nonaqueous, glycerol solution which retained the phenol in the perivesical fat for a longer

Management of Detrusor Instability


period of time. Because of the high complication rate, many physicians consider previous pelvic surgery or pelvic irradiation to be contraindications for this treatment. The high risk for impotence in males is also a relative contraindication for injection. D.


The theory underlying cystolysis is that adverse effects can be avoided by affecting only the terminal nerve fibers entering the bladder. The technique of cystolysis is to divide the superior vesical vessels and the ascending branches of the inferior vesical vessels in the posterior aspect of the bladder. The dissection is made down to the level of the trigone. Hunner in 1918 described a procedure of freeing the bladder from its surrounding tissue in order to alleviate irritative symptoms. He reported long-term success of 73% in 19 patients who underwent the procedure. These results were not reproduced in other studies that followed. Worth et al. reported that of 10 patients who had cystolysis, three were cured while the other seven had partial or no improvement (79). A 7-year follow-up showed that the three patients who were cured had no further symptoms (80). The procedure has been performed laparoscopically with similar results (81). Albers et al. reported long-term follow-up in 11 patients of whom one was cured, four had a partial response, and seven did not respond at all (82). Because there is disruption of sensory and motor fibers during the procedure, most patients lose some of their detrusor contraction ability, and in the Freiha report all patients augmented their detrusor contraction by straining after the procedure (83). Because of the inconsistent results, cystolysis is rarely employed at this time. E.

Percutaneous Neuromodulation

Electrical stimulation (ES) for the treatment of urinary incontinence has evolved over the past 40 years. In 1963 Caldwell experimented with implantation of an electrode in the periurethral area with the result that 50% of patients were cured or improved of their incontinence (84,85). Since then, various techniques have emerged but the response rate has not changed significantly. Although the mechanism of action of ES has been investigated in animal models, the mechanism of action remains unclear in humans. Several theories have been proposed to explain the effect of ES. 1. More than 100 years ago Griffith demonstrated relaxation of detrusor muscle in response to activation of the pudendal nerve (86). In humans it was shown that sensory input through the pudendal nerve inhibits detrusor activity (87). Thus, pudendal nerve stimulation and enhancement of external sphincter tone may serve to control bladder overactivity and facilitate urine storage. 2. Stimulation of afferent sacral nerves in either the pelvis or lower extremities increases the inhibitory stimuli to the efferent pelvic nerve and reduces detrusor contractility (88). The assumption is that at low bladder volumes there is stimulation of the hypogastric nerve through activation of sympathetic fibers, and at maximal bladder volume direct stimulation of the pudendal nerve nuclei in the spinal cord. Another theory is that there is supraspinal inhibition of the detrusor (89 –91). 3. The bladder responds to neural stimulation initially with rapid contraction followed by slow, longer-lasting relaxation. With recurrent, repetitive stimuli there are decay and downregulation of the bladder’s response, thus reducing the detrusor’s over activity. F.

The Stoller Afferent Nerve Stimulator

The Stoller afferent nerve stimulator (SANS; UroSurge, Coralville, IA) utilizes the peroneal nerve for transcutaneous access to the S3 spinal cord region. Originally, McGuire reported the


Lai et al.

first study with ES of the posterior tibial nerve on 1983 (92). Of 22 patients with UI, 55% were cured and 32% improved. Peripheral nerve stimulation is performed by insertion of a 34-gauge needle three fingerbreadths (4 cm) cephalad to the medial malleolus. The needle is advanced at a 308 angle toward the ankle. A ground electrogram pad is placed on the same side, and the needle is connected to the SANS device, a 9-V AC monopolar generator. Pudendal nerve reflex stimulation at the frequency of 35– 40 Hz improves reinnervation and conversion of fast-twitch into slow-twitch fibers. Stimulation of the detrusor muscle by 2 –10 Hz leads to reflex inhibition. The SANS device is programmed to utilize both of these effects by generating a stimulus at the frequency of 20 Hz. The stimulation is 0.5 –10 mA with a fixed pulse length of 200 msec. Proper stimulation is recognized by great toe flexion or by fanning or flexion of the other digits. In most cases the stimulation is applied for 30 min with repeated sessions that vary in different protocols. Klingler et al. (93) with a protocol of treatments four times a week for 12 weeks in a group of 15 patients (11 women, four men) with a mean follow-up of 10.9 months demonstrated reduction in pelvic discomfort in all patients. On the basis of patient complaints of urgency and frequency, 46.7% of patients were defined as cured, 20% as improved, and 33.3% as nonresponders. Urodynamic evidence of bladder instability was eliminated in 76.9%. In all patients maximal capacity of the bladder was increased, and there was an increase in the volume associated with first sensation and first desire to void. There was a statistically significant difference in the daytime and nighttime frequencies before and after the treatment (P ¼ .002). Patients with prolonged a history of interstitial cystitis and those with a structural abnormality in the bladder wall did not seem to benefit from the treatment. No side effects or complications were observed except transient hematomas at the puncture site. Govier et al. (94) used the same SANS device on a group of 53 patients. More than 90% of the patients were women. Needle placement, amperage, stimulus frequency, and stimulus duration were the same as in the previous study. The treatment protocol was for 12 weekly sessions of 30 min duration each. Eighty-nine percent of participants completed the 12-week study. Of the 53 patients, 71% were either cured or improved and were started on a long-term treatment. The patients had on average a 25% reduction in mean daytime and 21% reduction of mean nighttime frequency, with a 35% reduction of average UI events. There was a statistically significant improvement in the QOL and pain measurement indexes. Three adverse events were noted: throbbing pain in the puncture site, right foot pain, and stomach discomfort. During the study one patient was found to have cardiomyopathy, but it was not believed to be related to the percutaneous procedure. The effect of the SANS device lasted after cessation of the initial stimulation session. Proper selection of the stimulation site is very simple, and some suggest that the patients themselves can perform future stimulations. The SANS was approved by the FDA in February 2001. G.

Sacral Neuromodulation

Sacral nerve stimulation stemmed from research focusing on the effect of the voiding reflex, the influence of sacral nerves on the voiding pattern, and central inhibitory control on micturition (95,96). It is thought that sacral nerve stimulation induces a reflex inhibitory effect on the detrusor through afferent and efferent fibers in the sacral nerves (97). As previously stated the first attempt of neuromodulation through sacral ES was carried out in the 1960s by Caldwell (95). About two decades later the technique has gained popularity for various lower urinary tract dysfunctions, and especially for uninhibited bladder contractions (98–101). All candidates are evaluated for response to sacral nerve stimulation. The goal of the first stage is to identify a percutaneous localization of the sacral nerve, which provides the best neuroanatomical response.

Management of Detrusor Instability


To localize the S3 foramen the sacral area needs to be sterilely prepared and draped. The sciatic notches can be palpated either uni- or bilaterally. The S3 foramen can be found one finger off the midline at the level of the sciatic notch. Local anesthetic is injected into the skin and the subcutaneous fat with a 2-inch 22-gauge needle all the way down to the sacrum. Injection of the local anesthetic to the foramina canal does not cause loss of motor response. Probing the relevant area with a 21-gauge needle identifies the foramen. Once the foramen is identified, the margins of the opening needs to be outlined. The nerve passes at the superior medial aspect of the foramen (97). The response is indicated by flexion of the ipsilateral great toe and contraction of the levator ani muscles. To facilitate the recognition of the stimulatory effect, two electrodes can be positioned in the urethra and the anal canal. These electrodes record excitation of the external urethral sphincter and the pelvic floor, respectively. Later, the electrode is firmly secured and a trial of continuous stimulation is undertaken for a period of 3– 7 days. During this time the stimuli are 210 msec, frequency 10 Hz, and amplitude ranging from 0.5 to 10 V, self-managed and adjusted by the patient. Patients who respond favorably and demonstrate a 50% reduction in their incontinent episodes are candidates for surgical implantation of the stimulator. A prospective multicenter randomized study was carried out from December 1993 to September 1999 utilizing the InterStim System (Medtronic Inc., Minneapolis, MN) (102). A group of 96 patients (85 females, 11 males) were evaluated with an average follow-up time of 30.8 months. Baseline assessment included (a) medical and urological history, (b) urodynamic testing, and (c) a 3-day voiding diary. Patients’ voiding diaries served as the primary outcome measure. Seventeen of the 96 patients did not benefit from the device, and in 11 of them the device was explanted. Twenty-six patients were defined as cured and had no episodes of UI. Thirty-six had a significant improvement. With the average follow-up of 30.8 months, there were a statistically significant reduction of leaking episodes, a decrease in the severity of the leaking episodes, and a decrease in use of diapers or other absorbent pads (P , .0001). Concomitantly, statistically significant effects were an increase in average volume per void, an increase in maximal voided volume, improved urine stream, improved sensation of “emptying” postvoid, decreased number of voids per day, and reduced pelvic discomfort. The majority of patients who had a successful clinical outcome at 6 months demonstrated a sustained beneficial effect later on. Adverse effects were pain at the pulse generator site that in most cases was because of interference with a bony structure or belt line, infection, pain at lead site, and lead migration. Baseline demographic parameters including age and gender were not predictive of clinical outcome. While these results are encouraging, it should be emphasized that 50% of patients do not respond to the test stimulation. Seventeen percent to 20% of those who initially have a favorable response will proceed with implantation later, but will not benefit from the device, and some of them will require an additional procedure to remove the stimulator. All in all, about one-third of patients will have a long-term response to the treatment. H.

Detrusor Myectomy

Spontaneously formed bladder diverticuli are seen frequently in patients with neurogenic bladders and in patients with long standing bladder outlet obstruction. The observation of this phenomenon led Cartwright and Snow in 1989 to suggest deliberate removal of the detrusor muscle in order to create a wide-mouthed iatrogenic diverticulum (103,104). The goal of the procedure is to increase bladder capacity, reduce bladder storage pressure, attenuate the amplitude of the uninhibited bladder contractions, and thus reduce episodes of urinary urgency, urge incontinence, and frequency. The procedure was termed “autoaugmentation” in contrast to “augmentation,” which applied to use of gastrointestinal tissue to augment the bladder. Autoaugmentation was designed to avoid the inherent problems encountered when applying small or large bowel to the genitourinary


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tract. The procedure is performed under general or regional anesthesia, and the bladder is exposed extraperitoneally after filling by gravity via a transurethral catheter. Indigo Carmine or Methylene Blue mixed with saline may improve the view and aid in defining the dissection level. The peritoneum is displaced cephalad, and 25% of the detrusor muscle at the bladder’s dome is removed by blunt and sharp dissection, exposing the underlying bulging urothelium. Cartwright recommends doing this part of the dissection with a two-channel urodynamic catheter to ensure a 30–50% increase in the bladder’s volume under 20–40 cmH2O. Mucosal tears may be repaired by figure of eight 6/0 absorbable sutures. The raised detrusor flaps may be anchored to the psoas muscle, although they are more often than not resected (105–108). Swami et al. (107) recommended making a small peritoneal incision so that the great omentum may be pulled over and attached to the bladder’s anterior wall to prevent inflammatory reaction and fibrosis. In their experience, patients who had an omental flap had less perivesical fibrosis if another intervention was required, whereas patients who had no omental flap were found to have the mucosa firmly adherent to the retropubic area when undergoing a subsequent procedure. Other techniques employ demucosalized, colonic, gastric, and sigmoid tissue to cover the urothelial diverticulum (109–111). Some physicians prefer not to cover the myectomized area, assuming the procedure will reduce overall compliance (106). After the procedure a catheter is left in place for 2–7 days. Before removal of the catheter a cystogram is performed. Cartwright (103) recommends periodically distending the bladder 1 week after the procedure in order to prevent contraction. However, most recent studies have not employed this technique. After removal of the catheter the patient is instructed to do timed voiding, and postvoid residuals are checked. If the patient is unable to void, he or she is instructed to perform clean intermittent catheterization (CIC) q3h during the day and q4h at night. Although satisfactory results have been achieved with laparoscopic autoaugmentation, only a limited number of patients have undergone the procedure (112–114). Autoaugmentation may be appropriate for patients with moderately reduced bladder capacity in need of a bladder augmentation no more than 50% of their original volume. The reported success rates of the procedure reach 80% (105,107,115). Swami et al. (107) reported an overall success rate of 63%, with a 70% success rate for patients with idiopathic instability and a 50% success rate for those with neuropathic instability. These results are inferior to the results obtained by enterocystoplasty; however, the morbidity and complication rates are lower. Leng et al. (108) compared the outcomes of two groups, 32 who had enterocystoplasty and 37 who had detrusor myectomy, and concluded that these two techniques offered comparable results. However, the enterocystoplasty group had a better outcome and needed fewer revisions than the myectomy group. The complications rate in the enterocystoplasty group and the detrusor myectomy group were 20% and 3%, respectively. Leng et al. (108) emphasized that detrusor myectomy had minimal morbidity and did not preclude subsequent bowel augmentation if subsequently required. Complications reported after autoaugmentation are urinary retention and bladder perforation. Urinary retention requiring CIC is observed in ,15% of patients with no underlying urological deficit (107). The risk for bladder perforation is higher in patients who are required to perform CIC, especially in the early postoperative period. I.


The favorite, and still most commonly used technique for increasing bladder capacity and compliance is the enterocystoplasty. Goodwin introduced enterocystoplasty in 1958 (116). The goal of enterocystoplasty is to create a reservoir that will maintain low pressure and thus prevent upper urinary tract deterioration. The low-pressure compliant system buffers the increase in intravesical pressure secondary to uninhibited contractions and ameliorates the sensation of urgency. Comorbidities such as vesicoureteral reflux and bladder outlet incompetence may be

Management of Detrusor Instability


treated concomitantly. The augmented bladder should hold sufficient volume to be comfortable for at least 4 h. On the other hand, the augmentation should be to a volume that will enable adequate drainage of the bladder. The augmentation creates a spherical shape, so the bladder’s volume is determined by its radius according to the formula V ¼ 4/3R3. This formula can be employed when calculating the additional volume that is needed for augmenting the bladder and the length of bowel that is required (117). Various segments of bowel may be used for enterocystoplasty. Each segment of bowel has its own advantages and disadvantages. No matter which segment of bowel is chosen for the enterocystoplasty, several key points need to be remembered: 1. 2. 3.



The chosen segment of bowel needs to be detubularized. No nonabsorbable sutures should be applied to the intraluminal surface of the augment. The segment of bowel chosen needs to have a sufficient mesentery to reach the true pelvis and be sewn to the bladder which has been divided either sagitally or transversely (118,119). When the procedure is concluded, a cystostomy tube should be left through the wall of the native bladder and a drain should be left near the anastomotic site.

Choice of Bowel Segments

a. Ileum. When ileum is chosen, a segment 15 cm proximal to the ileocecal valve is isolated. The total segment needs to be 20– 40 cm long and may be formed into a U-shaped patch after it is detubularized. If a larger augmentation is needed the patch can be formed into an “S” or W-shaped patch. The configuration of the ileum to the desired shape may be achieved by a running 3-0 absorbable suture or by using absorbable staples. The patch is anastamosed to the bladder with a 3-0 running absorbable suture. b. Cecum. Cecocystoplasties have been performed since the early 1950s. In the last decade they were replaced by either ileocystoplasty or ileocecocystoplasty. In ileocecocystoplasty a segment of ileum and cecum of equivalent length are mobilized and transected. After detubularization through the ileocecal valve, the bowel is anastamosed to itself and then as a patch on the bivalved bladder. In the Mainz ileocecocystoplasty a segment of ileum twice the length of the cecum is isolated and anastamosed to itself in a U-shape and later to the cecum to create a bigger patch. If needed, a tubularized segment of ileum may be kept as a chimney serving for reanastomosis of the ureters. c. Sigmoid. Sigmoidcystoplasty is employed most often in cases in which the mesentery of the small bowel is too short and makes the anastomosis to the bivalved bladder impossible. A 15 to 20-cm length of sigmoid colon is mobilized and resected. The sigmoid is opened on its antimesenteric side and is formed to either a U-shape or an S-shape. Another technique is to close the two ends of the resected sigmoid and to open the antimesenteric side and then anastomose it to the bivalved bladder (120). d. Stomach. Two techniques are available for performing gastrocystoplasty. The first is to use the antrum with the blood supply of the left gastroepiploic artery. The gastric pedicle is passed through a window in the transverse mesocolon and mesentery of the distal ileum. The stomach is reanstomosed by a Billroth I gastroduodenostomy. The second technique is to use the gastric body which is mobilized on either the right or left gastroepiploic vessels. A segment of 10 –20 cm of the greater curvature is mobilized and transected in a wedge shape that should not reach the lesser curvature in order to avoid injury to the vagus nerve. Because of the abundance of acid-secreting cells in the stomach, patients who undergo a gastrocystoplasty are more likely to suffer later with dysuria and other irritative symptoms. In most cases the bowel patch can be anastamosed to a bivalved bladder. In certain instances, when the major complaint is pelvic pain associated with interstitial cystitis, some


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physicians perform a supratrigonal cystectomy. It has been reported that leaving the trigone results in persistent complaints of pelvic discomfort (121). It should be noted, however, that in some patients, complaints persisted even after complete cystectomy (122). Success rates of enterocystoplasty vary considerably and range from 25% to 95% (118,119,122– 127). The wide range reflects the fact in many series a number of the patients who were treated had interstitial cystitis. These patients, as a rule, gained less from the procedure. Another reason for the wide discrepancy is the inconsistency in defining and measuring success. In some of the studies success rates vary considerably depending on the authors’ definitions of success and the patients’ view of the outcome (126). The complication rate after enterocystoplasty may be considerable. Flood et al. (127) report of 116 patients with early and late complication rates of 22% and 44%, respectively, and found the following: 2.

Early Complications

Bowel obstruction—prolonged ileus after entercystoplasty—is infrequent and occurs in 3% of patients. In other reports in which prolonged ileus was regarded as .5 days, 10% of the patients had prolonged ileus. However, at least some of these patients had some neurologic deficiency (128). The segment of bowel that is used does not impact the duration of the ileus. Fistula—may occur in 15% of patients. The most common site for leakage is the anastomotic suture line between the bladder and the augment. Other possible sites may be the suprapubic tube puncture site and the urethra in cases of concomitant sphincteric weakness. In most cases the leakage ceases by itself with proper drainage. Only 1– 2% require an additional procedure to obliterate the fistula (127). Wound infection—as with other clean contaminated procedures, the wound infection rate is 3 –5%. 3.

Late Complications

Diarrhea and bowel dysfunction may develop in 10– 16% of patients after enterocystoplasty. Patients may complain of increased bowel frequency and fecal incontinence. The removal of the ileocecal valve is likely to cause diarrhea and may decrease transit time along the gastrointestinal tract and cause bacterial backflow into the ileum and malabsorbtion of fat, B12, and bile salts (129,130). Because vitamin B12 is absorbed exclusively in the ileum, resection of the distal ileum may result in B12 deficiency, and subsequent megaloblastic anemia and neurologic impairment. Therefore, the use of the distal 10– 20 cm of the ileum should be avoided, if possible. Because body stores of B12 are significant, deficiency may not be apparent for as long as 5 years. B12 levels should be monitored, and supplements should be given to ileocystoplasty patients if levels decline. Bladder compliance following augmentation should be monitored because even detubularized segments of colon and ileum may cause peristaltic contractions and raise the bladder pressure to .40 cmH2O (131). Colonic segments are more prone than small bowel to cause significant contractions (132). Other metabolic alterations may also occur. In patients who undergo enterocystoplasty, acid is reabsorbed from the urine by the intestinal segments, which results in increased chloride and decreased bicarbonate in the serum (133). In patients with normal renal function, frank acidosis does not occur, but a continuous loss of bony buffers may lead to bone demineralization (134). Bicarbonate supplementions may be required. Use of gastric segments may cause hypokalemic hypochloremic metabolic alkalosis but may be the only option for patients with renal deficiency (135). Another unique side effect associated with use of gastric mucosa is the hematuria dysuria syndrome. The syndrome may affect up to 35% of the patients. H2 blockers and hydrogen ion pump blockers may attenuate such symptoms.

Management of Detrusor Instability


Increased risk of adenocarcinoma in the urinary tract was observed in ureterosigmoidostomies. The teratogenic compound is thought to be made up of nitrosocompounds that result from the mixture of feces and urine. Nitrosocompounds are also observed in bladder substitutions and bladder augmentations. Another factor that can increase production of nitrosocompounds is the inflammatory reaction at the anastomotic site that produces cellular proliferation and increased formation of free radicals. Tumor development occurs regardless of the segment of bowel utilized (136 –138). There is a latency period until bladder neoplasms develop; therefore annual surveillance with cytology and/or cystoscopy should start 5– 10 years after formation of the augmentation. Bladder and kidney calculi formation of bladder stones occurs in 8–50% (137,138). Most stones are struvite and are the result of inadequate bladder drainage, retention of mucus, and infection associated with urea-splitting organisms. Struvite stones have not been noted in gastrocystoplasties. Formation of stones may be decreased by proper bladder emptying, adequate bladder irrigation, and eradication of urea-splitting bacteria. About 6% of the patients form kidney stones as result of reflux of contaminated urine and mucus to the upper collecting system. Bacteruria is a common phenomenon after bladder augmentation, especially if there is a need for CIC. Treatment of the isolated bacteria should be applied only if the patient is symptomatic or when positive cultures show urea splitting organisms that may predispose the patient to bladder calculi. The incidence of post augmentation UTIs is 4–13% (127,139). The gastrointestinal segment used for augmentation continues to produce mucus, which may impede the bladder’s drainage and may be a nidus for stone formation. Colonic segments produce the largest amount of mucus, and gastric segments produce the least. Inflammatory responses to UTI in the augmented bladder increase mucus formation. To prevent mucus buildup, routine bladder irrigation is recommended. Instillation of N-acetylcysteine into the bladder may help dissolve the mucus (140). N-acetylcysteine is not approved for this purpose by the Food and Drug Administration. Bladder perforations have been reported in numerous studies with an incidence of 3–9% (127,139,141). Some of the perforations were attributed to improper technique or noncompliance with CIC. However, some of the perforations were regarded as “spontaneous” in patients who were not catheterizing at all. Spontaneous perforations may be the result of a chronic inflammatory process in the bladder, intestinal ischemia, or uncontrolled increased intravesical pressure. Any patient with an enterocystoplasty who exhibits signs of peritonitis should be suspected to have a bladder perforation. Urinary retention that necessitates CIC occurs in as many as 50% of patients (123,127,142). The rate of retention correlates with the underlying pathology and the ratio of the bowel’s surface area to the entire augmented bladder. All patients need to be informed that they might need to do CIC after the operation and to learn how to perform it prior to the operation. J.

Urinary Diversion

There is almost no indication for performing urinary diversion in patients with OAB, in the absence of a neurogenic cause. In case of unremitting pain such as in IC or irradiated bladders a supratrigonal cystectomy should suffice. Diversion may be justified in a subcategory of patients with “end-stage” bladders combined with severe sphincteric damage or pelvic pain. Description of the various diversion options is beyond the scope of this chapter.


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Lai et al. twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin. BJU Int 2000; 85(7):793– 798. Appell RA, Diokno A, Antoci J. One-year, prospective, open-label trial of controlled-release oxybutynin for overactive bladder in a community-based population [abstract]. Neurourol Urodyn 2000; 19:526. Abstract 117. Thomas TM, Plymat KR, Blannun J, Meade TW. Prevalence of urinary incontinence. BMJ 1980; 281(6250):1243– 1245. Chamberlain TM, Stephenson DW, Appell RA. Urinary incontinence in the long-term care patient. Consul Pharm 1990; 5:173. Appell RA, Sand P, Domchowski R, Anderson R, Zinner N, Lama D, Roach M, Miklos J, Saltzstein D, Boone T, Staskin DR, Albrecht D. Overactive Bladder: Judging Effective Control and Treatment Study Group. Prospective randomized controlled trial of extended-release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder: results of the OBJECT study. Mayo Clin Proc 2001; 76(4):358– 363. Detrol LA physician package insert. Available at: http://www.pharmacia.com. Accessed 4/3/2002. Olsson B, Szamosi J. Multiple dose pharmaco*kinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine. Clin Pharmaco*kinet 2001; 40(3):227–235. Van Kerrebroeck P, Kreder K, Jonas U, Zinner N, Wein A; Tolterodine Study Group. Tolterodine once-daily: superior efficacy and tolerability in the treatment of overactive bladder. Urology 2001; 57(3):414– 421 Bumpus H. Interstitial cystitis: its treatment by overdistention of the bladder. Med Clin North Am 1930, 1495. Hanno PM, Wein AJ. Interstitial cystitis. J Urol 1987; 138: 595–596. Hanno PM, Wein AJ. Conservative therapy of interstitial cystitis. Semin Urol 1991; 9:143 – 147. Sehn J. The ultrastructural effect of prolonged distension on the neuromuscular apparatus of the bladder (MSc thesis). Oxford: University of Oxford, 1976. Keay S, Zhang C, Marvel R, Chai T. Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor: sensitive and specific urine markers for interstitial cystitis. Urology 2001; 57:104. Rofeim O, Shupp-Byrne D, Mulholland GS, Moldwin RM. The effects of hydrodistention on bladder surface mucin. Urology 2001; 57:130. Chai TC, Zhang CO, Shoenfelt JL, Johnson HW Jr, Warren JW, Keay S. Bladder stretch alters urinary heparin-binding epidermal growth factor and antiproliferative factor in patients with interstitial cystitis. J Urol 2000; 163:1440– 1444. Dunn M, Ramsden PD, Roberts JB, Smith JC, Smith PJ. Interstitial cystitis, treated by prolonged bladder distension. Br J Urol 1977; 49:641 – 645. Ramsden PD, Smith JC, Dunn M, Ardran GM. Distension therapy for the unstable bladder: later results including an assessment of repeat distensions. Br J Urol 1976; 48:623 – 629. Jorgensen L, Mortensen SO, Colstrup H, Andersen JT. Bladder distension in the management of detrusor instability. Scand J Urol Nephrol 1985; 19:101– 104. Pengelly AW, Stephenson TP, Milroy EJ, Whiteside CG, Turner-Warwick R. Results of prolonged bladder distension as treatment for detrusor instability. Br J Urol 1978; 50:243– 245. Ingelman-Sundberg A. Partial denervation of the bladder. A new operation for the treatment of urge incontinence and similar conditions in women. Acta Obstet Gynaecol Scand 1959; 38:487. Cespedes RD, Cross CA, McGuire EJ. Modified Ingelman – Sundberg bladder denervation procedure for intractable urge incontinence. J Urol 1996; 156:1744 – 1747. Warrell DW. vagin*l denervation of the bladder nerve supply. Urol Int 1977; 32: 114– 116. Hodgkinson CP, Drukker BH. Infravesical nerve resection for detrusor dyssynergia. The Ingelman– Sundberg operation. Acta Obstet Gynaecol Scand 1977; 56:401 – 408. Susset JG, Pinheiro J, Otton P, Brindle F, Bertrand G. Selective phenolization and neurotomy in the treatment of neurogenic bladder dysfunction due to an incomplete central lesion. J Urol Nephrol (Paris) 1969; 75:12(suppl):502 (In French).

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Blackford HN, Murray K, Stephenson TP, Mundy AR. Results of transvesical infiltration of the pelvic plexuses with phenol in 116 patients. Br J Urol 1984; 56:647 –649. Harris RG, Constantinou CE, Stamey TA. Extravesical subtrigonal injection of 50 per cent ethanol for detrusor instability. J Urol 1988; 140:116. Ramsay IN, Clancy S, Hilton P. Subtrigonal phenol injections in the treatment of idiopathic detrusor instability in the female—a long-term urodynamic follow-up, Br J Urol 1992; 69:363– 365. McInerney PD, Vanner TF, Matenhelia S, Stephenson TP. Assessment of the long-term results of subtrigonal phenolisation. Br J Urol 1991; 67:586– 587. Chapple CR, Hampson SJ, Turner-Warwick RT, Worth PH. Subtrigonal phenol injection. How safe and effective is it?. Br J Urol 1991; 68:483– 486. Madjar S, Smith ND, Balzarro M, Appell A. Bupivacaine injections prior to subtrigonal phenolization: preliminary results. Presented at the 22nd Annual Meeting of the Society for Urodynamics and Female Urology, Annaheim, CA, 2001. Bennani S. Evaluation of sub-trigonal injections in the treatment of the hyperactive bladder. Ann Urol 1994; 28:13 – 19. Worth PH, Turner-Warwick R. The treatment of interstitial cystitis by cystolysis with observations on cystoplasty. Br J Urol 1973; 45:65 –71. Worth PH. The treatment of interstitial cystitis by cystolysis with observations on cystoplasty. A review after 7 years. Br J Urol 1980; 52:232. Lucas MG, Thomas DG. Endoscopic bladder transection for detrusor instability. Br J Urol 1987; 59:526– 528. Albers DD, Geyer JR. Long-term results of cystolysis (supratrigonal denervation) of the bladder for intractable interstitial cystitis. J Urol 1988; 139:1205 – 1206. Freiha FS, Stamey TA. Cystolysis: a procedure for the selective denervation of the bladder. J Urol 1980; 123:360 – 363. Caldwell K. The electrical control of sphincter incompetence. Lancet 1963; ii:174– 175. Caldwell KP. The Treatment of Incontinence by Electronic Implants. London: Royal College of Surgeons of England, 1967. Griffiths J. Observation on the urinary bladder and urethra. Part 2. The nerves. Part 3. Physiological. J Anat Physiol 1895; 29/61:254– 261. Vodusek DB, Libby J. Detrusor inhibition induced by stimulation of pudendal nerve afferents. Neurourol Urodyn 1986; 5:381 – 384. Zvara P, Sahi S, Hassouna M. An animal model for the neuromodulation of neurogenic bladder dysfunction. Br J Urol 1988; 82:267 – 271. Lindstrom S, Fall M, Carlsson CA, Erlandson BE. The neurophysiological basis of bladder inhibition in response to intravagin*l electrical stimulation. J Urol 1983; 129:405– 410. Fall M, Lindstrom S. Electrical stimulation. A physiologic approach to the treatment of urinary incontinence. Urol Clin North Am 1991; 18:393 – 407. Janez J, Plevnik S, Suhel P. Urethral and bladder responses to anal electrical stimulation. J Urol 1979; 122:192 – 194. McGuire EJ, Zhang SC, Horwinski ER, Lytton B. Treatment of motor and sensory detrusor instability by electrical stimulation. J Urol 1983; 129:78– 79. Klingler HC, Pycha A, Schmidbauer J, Marberger M. Use of peripheral neuromodulation of the S3 region for treatment of detrusor overactivity: a urodynamic-based study. Urology 2000; 56:766–771. Govier FE, Litwiller S, Nitti V, Kreder KJ Jr, Rosenblatt P. Percutaneous afferent neuromodulation for the refractory overactive bladder: results of a multicenter study. J Urol 2001; 165:1193–1198. Bradley WE, Timm GW, Chou SN. A decade of experience with electronic simulation of the micturition reflex. Urol Int 1971; 26:283– 302. Juenemann KP, Lue TF, Schmidt RA, Tanagho EA. Clinical significance of sacral and pudendal nerve anatomy. J Urol 1988; 139:74 – 80. Schmidt RA, Senn E, Tanagho EA. Functional evaluation of sacral nerve root integrity. Report of a technique. Urology 1990; 35:388 – 392. Schmidt RA. Treatment of unstable bladder. Urology 1991; 37:28– 32.

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Lai et al. Koldewijn EL, Rosier PF, Meuleman EJ, Koster AM, Debruyne FM, Van Kerrebroeck PE. Predictors of success with neuromodulation in lower urinary tract dysfunction: results of trial stimulation in 100 patients. J Urol 1994; 152:2071 –2075. Bosch JL, Groen, J. Sacral (S3) segmental nerve stimulation as a treatment for urge incontinence in patients with detrusor instability: results of chronic electrical stimulation using an implantable neural prosthesis. J Urol 1995; 154:504– 507. Chartier-Kastler E, Richard F, Denys P, Perrigot M, Bussel B, Chatelain C. S3 sacral neuromodulation in patients with chronic refractory miction disorders. Presse Med 1997; 26:466– 467 (In French). Janknegt RA, Hassouna MM, Siegel SW, Schmidt RA, Gajewski JB, Rivas DA, Elhilali MM, Milam DC, van Kerrebroeck PE, Dijkema HE, Lycklama a Nyeholt AA, Fall M, Jonas U, Catanzaro F, Fowler CJ, Oleson KA. Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence. Eur Urol 2001; 39:101– 106. Cartwright PC, Snow BW. Bladder autoaugmentation: partial detrusor excision to augment the bladder without use of bowel. J Urol 1989; 142:1050 – 1053. Cartwright PC, Snow BW. Bladder autoaugmentation: early clinical experience. J Urol 1989; 142:505– 508. Stohrer M, Kramer G, Goepel M, Lochner-Ernst D, Kruse D, Rubben H. Bladder autoaugmentation in adult patients with neurogenic voiding dysfunction. Spinal Cord 1997; 35:456 – 462. Stohrer M, Goepel M, Kramer G, Lochner-Ernst D, Rubben H. Detrusor myectomy (autoaugmentation) in the treatment of hyper- reflexive low compliance bladder. Urologe A 1999; 38:30–37 (In German). Swami KS, Feneley RC, Hammonds JC, Abrams P. Detrusor myectomy for detrusor overactivity: a minimum 1-year follow-up. Br J Urol 1998; 81:68 – 72. Leng WW, Blalock HJ, Fredriksson WH, English SF, McGuire EJ. Enterocystoplasty or detrusor myectomy? Comparison of indications and outcomes for bladder augmentation. J Urol 1999; 161:758– 763. Dewan PA, Stefanek W. Autoaugmentation gastrocystoplasty: early clinical results. Br J Urol 1994; 74:460– 464. Lima SV, Araujo LA, Vilar FO, Kummer CL, Lima EC. Nonsecretory sigmoid cystoplasty: experimental and clinical results. J Urol 1995; 153:651 – 654. Gonzalez R, Buson H, Reid C, Reinberg Y. Seromuscular colocystoplasty lined with urothelium: experience with 16 patients. Urology 1995; 45:124 – 129. Ehrlich RM, Gershman A. Laparoscopic seromyotomy (auto-augmentation) for non-neurogenic neurogenic bladder in a child: initial case report. Urology 1993; 42:175 –178. McDougall EM, Clayman RV, Figenshau RS, Pearle MS. Laparoscopic retropubic autoaugmentation of the bladder. J Urol 1995; 153:123 – 126. Siracusano S, Trombetta C, Liguori G, De Giorgi G, D’ Aloia G, Di Benedetto P, Belgrano E. Laparoscopic bladder auto-augmentation in an incomplete traumatic spinal cord injury. Spinal Cord 2000; 38:59– 61. Kennelly MJ, Gormley EA, McGuire EJ. Early clinical experience with adult bladder autoaugmentation. J Urol 1994; 152:303 – 306. Goodwin WE, Winter CC. Results of ileocystoplasty. J Urol 1958; 80:461– 466. Koff SA. The shape of intestinal segments used for reconstruction. J Urol 1988; 94:201 –203. Kockelbergh RC, Tan JB, Bates CP, Bishop MC, Dunn M, Lemberger RJ. Clam enterocystoplasty in general urological practice. Br J Urol 1991; 68:38 –41. Kay R, Straffon R. Augmentation cystoplasty. Urol Clin North Am 1986; 13:295– 305. Mitchell ME, Rink RC. Urinary diversion and undiversion. Urol Clin North Am 1985; 12:111– 122. Christmas TJ, Holmes SA, Hendry WF. Bladder replacement by ileocystoplasty: the final treatment for interstitial cystitis. Br J Urol 1996; 78:69 –73. Baskin LS, Tanagho EA. Pelvic pain without pelvic organs. J Urol 1992; 147:683– 686. Mundy AR, Stephenson TP. “Clam” ileocystoplasty for the treatment of refractory urge incontinence. Br J Urol 1985; 57:641 – 646.

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Goldwasser B, Webster GD. Augmentation and substitution enterocystoplasty. J Urol 1986; 135:215– 224. Luangkhot R, Peng BC, Blaivas JG. Ileocecocystoplasty for the management of refractory neurogenic bladder: surgical technique and urodynamic findings. J Urol 1991; 146:1340–1344. Awad SA, Al-Zahrani HM, Gajewski JB, Bourque-Kehoe AA. Long-term results and complications of augmentation ileocystoplasty for idiopathic urge incontinence in women. Br J Urol 1998; 81:569– 573. Flood HD, Malhotra SJ, O’Connell HE, Ritchey MJ, Bloom DA, McGuire EJ. Long-term results and complications using augmentation cystoplasty in reconstructive urology. Neurourol Urodyn 1995; 14:297– 309. Rink RC, Adams MC. Complications of augmentation in children and comparison of gastrointestinal segments. AUA Update Ser 1995; 14:122– 128. King L. Cystoplasty in children. In: King LR, Webster GD, eds. Bladder Reconstruction and Continent Urinary Diversion. 2nd ed. St. Louis: Mosby Year Book, 1991:115 – 125. Wood GA, Heathcote PS, Nicol DL. Bowel motility after enterocystoplasty. Br J Urol 1998; 81:565– 568. Sidi AA, Reinberg Y, Gonzalez R. Influence of intestinal segment and configuration on the outcome of augmentation enterocystoplasty. J Urol 1986; 136:1201 – 1204. Goldwasser B, Barrett DM, Webster GD, Kramer SA. Cystometric properties of ileum and right colon after bladder augmentation, substitution or replacement. J Urol 1987; 138:1007– 1008. Mitchell ME, Piser JA. Intestinocystoplasty and total bladder replacement in children and young adults: followup in 129 cases. J Urol 1987; 138:579 – 584. Koch MO, McDougal WS, Hall MC, Hill DE, Braren HV, Donofrio MN. Long-term metabolic effects of urinary diversion: a comparison of myelomeningocele patients managed by clean intermittent catheterization and urinary diversion. J Urol 1992; 147:1343 – 1347. Ganesan GS, Adams MC. Use of stomach for the reconstructionof the lower urinary tract in patientswith compromised renal function. In: American Academy of Pediatrics, Urology Section Meeting, New Orleans, 1991. Filmer RB, Spencer JR. Malignancies in bladder augmentations and intestinal conduits. J Urol 1990; 143:671– 678. Golomb J, Klutke CG, Lewin KJ, Goodwin WE, deKernion JB, Raz S. Bladder neoplasms associated with augmentation cystoplasty: report of 2 cases and literature review. J Urol 1989; 142:377– 380. Spencer JR, Filmer RB. Malignancy associated with urinary tract reconstruction using enteric segments. Cancer Treat Res 1992; 59:75– 87. Hollensbe DW, Rink RC. Comparison of different gastrointestinal segments for bladder augmentation. In: American Urological Association Meeting, Washington DC, 1992. Gillon G, Mundy AR. The dissolution of urinary mucus after cystoplasty. Br J Urol 1989; 63:372– 374. Elder JS, Snyder HM, Hulbert WC, Duckett JW. Perforation of the augmented bladder in patients undergoing clean intermittent catheterisation. J Urol 1988; 140:1159– 1162. Nurse DE, McCrae P, Stephenson TP, Mundy AR. The problems of substitution cystoplasty. Br J Urol 1988; 61:423 – 426.

13 Pharmacologic Management of Urinary Incontinence Alan J. Wein and Eric S. Rovner University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, U.S.A.



There are multiple mechanisms, some proven in concept but others more theoretical, through which a pharmacologic effect could facilitate bladder filling/urine storage. These include peripheral and central motor (efferent) and sensory (afferent) sites of action. Clinical uropharmacology of the lower urinary tract is based primarily on an appreciation of the innervation and receptor content of the bladder, the bladder outlet, and their related anatomic structures. The drugs or classes of drugs used for therapy of lower urinary dysfunctions were, in general, developed originally for their actions on other organ systems whose functions are controlled or affected by innervation or drug receptor interaction. The targets of pharmacologic intervention in the bladder body, base, or outlet include specific nerve terminals that alter the release a variety of neurotransmitters, receptors and receptor subtypes, cellular second-messenger systems, and ion channels. Peripheral nerves and ganglia, spinal cord, and supraspinal areas are also sites of action of some agents to be discussed. Despite disagreements on various details of neurophysiology, neuropharmacology, and neuromorphology, all “experts” undoubtedly would agree that, for the purposes of explanation and teaching, normal bladder filling and urine storage can be categorized as requiring the following: (a) accommodation of increasing volumes of urine at a low intravesical pressure and with appropriate sensation; (b) a bladder outlet that is closed at rest and remains so during increases in intraabdominal pressure; and (c) absence of involuntary bladder contractions. All types of therapy for storage disorders, regardless of whether the etiology is neurogenic or nonneurogenic, can be classified within a functional scheme derived from this simple concept. Using this classification, this presentation will summarize current thought regarding the efficacy of various types of drug therapy for incontinence in the female, borrowing liberally from similar prior presentations (1 – 8). As an apology to others in the field whose works are not specifically cited, it should be noted that references have generally been chosen because of their informational or review content and not because of originality or initial publication on a particular subject. 215



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Because autonomic innervation and receptor content are ubiquitous throughout the human body’s organ systems, there are no agents in clinical use that are purely selective for action on the lower urinary tract. Thus, the majority of side effects attributed to drugs facilitating bladder storage or emptying are the collateral effects on organ systems that share some of the same neurophysiologic or neuropharmacologic characteristics as the lower urinary tract. In general, drug therapy for all lower urinary tract dysfunction is hindered by a lack of uroselectivity (9). This concept describes a lack of selectivity of a drug for the lower urinary tract and is responsible for a given agent’s systemic side effects. Many of the drugs described in this chapter are highly effective agents in treating voiding dysfunction provided that the drug is administered in sufficient quantity. However, dose dependent systemic adverse effects can often limit the physician’s ability to maximally exploit a given drug’s therapeutic effects. Escalating dosages often lead to increasing collateral effects on other organ systems. This often impairs reaching the optimal dosage of the agent with resultant implications for an individual patient’s quality of life. Nevertheless, improvements in uroselectivity can be approached in a number of ways: receptor selectivity; organ selectivity; and alterations in drug delivery, metabolism, and distribution. Receptor selectivity may be of little use unless the receptor is not expressed or operative in other organs or pathways or unless a receptor subtype exists that is specific for the organ being treated or its neurologic connections. Organ specificity, however, is indeed the Holy Grail of drug therapy. The ideal organ-selective drug for the lower urinary tract would exert its desirable effects only on the bladder and/or urethra, thus eliminating collateral effects elsewhere in the body. Theoretically, the concept of organ specificity is very attractive but practically and clinically it is very difficult to achieve. Alternate drug delivery systems may be helpful by increasing the target concentration of an agent (intravesical therapy, e.g.) or by changing the metabolism of a drug to lower the concentration of a metabolite particularly productive of side effects. Certain drugs or their metabolites may be prevented from gaining access to a potentially troublesome site of activity (through the blood brain barrier, e.g.) either by virtue of their innate characteristics or by alteration. Given our current state of imperfection in this area, it is important to distinguish potential laboratory from real clinical effects, both beneficial and adverse, and it would be especially useful to construct a “therapeutic index” for each agent in clinical use, one that integrates its therapeutic and undesirable effects and requirements.




Relatively Pure Anticholinergic Agents

Most of the neurohumoral stimulus for physiologic bladder contraction is from acetylcholine (ACh)-induced stimulation of postganglionic parasympathetic muscarinic cholinergic receptor sites on bladder smooth muscle. Atropine and atropinelike agents inhibit normal and involuntary bladder contractions (IVC) of any etiology (10,11). Generally, volume to the first IVC increases, the amplitude of the IVC decreases, and the total bladder capacity increases (12). However, although the volume and pressure thresholds at which IVC is elicited may increase, the “warning time” (the time between the perception that an IVC is about to occur and its occurrence) and the ability to suppress the IVC do not increase. Therefore, to optimally suppress urgency and incontinence, pharmacologic therapy must be combined with behavioral modification. Anticholinergic agents do not significantly alter bladder compliance in normal individuals or in those with detrusor overactivity in whom the initial slope of the filling curve on cystometry is normal

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prior to the IVC (5). The effect of pure antimuscarinics in patients who exhibit only decreased compliance has not been well studied. Andersson points out that, while it is widely accepted that there is no sacral parasympathetic outflow to the bladder during filling, antimuscarinic drugs increase and anticholinesterase inhibitors decrease bladder capacity (13). Antimuscarinic drugs seem to affect the sensation of urgency during filling, suggesting ongoing ACh-mediated stimulation of detrusor tone. If this is the case, agents that inhibit ACh release or activity should contribute to bladder relaxation or maintenance of low bladder tone during filling, with a consequent decrease in filling and storage symptomatology unrelated to the occurrence of an IVC. Outlet resistance does not seem to be clinically affected by anticholinergic agents. The designations M1 through M5 are used to describe the pharmacologic and molecular subtypes of muscarinic ACh receptors (14). Human urinary bladder smooth muscle contains a mixed population of M2 and M3 subtypes, with a predominance of M2 receptors (80% of the total muscarinic receptor population) (15). While the minor population of M3 receptors is believed to be primarily responsible for mediating bladder contraction, experimental evidence suggests that M2 receptors are also involved in bladder contractility in some species and in certain types of LUT dysfunction (7,15 – 17). As alluded to earlier, the clinical utility of available antimuscarinic agents is limited by a lack of selectivity that is responsible for the classic peripheral anticholinergic side effects. Although M3-selective agents have the potential to eliminate some of these side effects, the M3 receptors in lower urinary tract tissues appear identical to those elsewhere in the body (14). There may, however, be some heterogeneity among M3 receptors, prompting many pharmaceutical companies to search for the “ideal” antimuscarinic that would be relatively specific for the muscarinic receptors that regulate bladder contractility. The potential side effects of all antimuscarinic agents include inhibition of salivary secretions, blockade of the sphincter muscles of the iris and the ciliary muscle of the lens to cholinergic stimulation, tachycardia, drowsiness, cognitive dysfunction, inhibition of gut motility, and inhibition of sweat gland activity. Agents that possess ganglionic blocking activity may also cause orthostatic hypotension and erectile dysfunction at the high doses generally required for manifestation of nicotinic activity. In general, antimuscarinic agents are contraindicated in patients with narrow-angle glaucoma and should be used with caution in patients with significant bladder outlet obstruction. Detailed efficacy and tolerability data for several antimuscarinics are reviewed below. 1.

Atropine sulfate (DL-hyoscyamine)

This agent is rarely used to treat OAB because of its adverse systemic effects (7). The pharmacologically active portion of the racemic mixture of atropine is L-hyoscyamine. This agent and hyoscyamine sulfate are reported to produce anticholinergic actions and side effects similar to other belladonna alkaloids. Hyoscyamine sulfate is also available in a sublingual formulation. The formulation offers a theoretical advantage, but controlled studies of its effects on bladder hyperactivity are lacking (7). 2. Propantheline Bromide This is a nonselective antimuscarinic that, as a quaternary ammonium compound, has a low and varying biological availability (11). The usual adult dose is 15 –30 mg every 4 –6 h, but often titration is necessary and higher doses are required. Few evaluable data on the drug’s effectiveness in treating bladder overactivity are available. The Agency for Health Care Policy and Research (AHCPR) Urinary Incontinence Guideline Panel reviewed five randomized controlled trials (RCTs) of propantheline (18). Of the total number of patients enrolled, 82%


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were female. Reports of cure ranged from 0% to 5% (all figures refer to percent effect on drug minus percent effect on placebo), reductions in urge incontinence ranged from 0% to 53%, side effects ranged from 0% to 50%, and dropouts ranged from 0% to 9%. Controlled randomized trials were also reviewed by Thu¨roff et al. (19) who reported a positive but variable response. 3. Tolterodine Tartrate This agent was developed specifically for treatment of overactive bladder. It is not receptor specific, but it and its primary metabolite have selectivity for the bladder over salivary gland selectivity in some experimental models (20,21). Clinically it seems to have a favorable side effect-profile not only with respect to dry mouth but with bowel and CNS effects as well (15). A number of clinical trials have evaluated the efficacy and tolerability of tolterodine. Stahl and colleagues first studied the effect of a single 6.4-mg dose on bladder and salivary function and found that its inhibitory effect on bladder function persisted up to 5 h (22). Stimulated salivation, however, was inhibited only near the time of peak serum levels. At 5 h after administration, the effects on the bladder were maintained, but no significant effects on salivation were detected. Appell reported on a pooled analysis of 1120 patients in whom tolterodine (1 or 2 mg BID) was compared with immediate release oxybutynin (5 mg 3 TID) or placebo (23). Compared with placebo, both active drugs significantly decreased the number of incontinent episodes and micturitions occurring in 24 h and increased the volume voided per micturition. Mean episodes of urge urinary incontinence decreased from 40% to 60% compared to baseline, and frequency of urination decreased by 20%. The 2-mg dose of tolterodine and the 5 mg (TID) dose of oxybutynin were equally efficacious, but tolerance was significantly better with tolterodine when adverse events such as dry mouth (frequency and intensity), dose reductions, and patient withdrawals were considered. Chancellor and associates conducted a large double-blind study comparing tolterodine (2 mg BID) with placebo (24). Tolterodine reduced urge incontinence episodes and also produced significant reductions in micturition frequency and pad use compared with placebo. Of tolterodine treated patients, 2% reported severe dry mouth and 10% reported moderate dry mouth compared with 0% and 2%, respectively, of placebo patients. Mild dry mouth was reported by 18% of drug-treated patients and by 6% of placebo-treated patients. Constipation was reported by 7% of tolterodine recipients and 4% of placebo recipients. The profile and frequency of other adverse events in the two treatment groups were similar. CNS adverse events were not significantly different between the tolterodine and placebo groups. Several other studies have reported similar findings with respect to tolterodine’s efficacy and tolerability (25,26). Tolterodine is now available in a once-daily formulation. The approval of this formulation was based on a large-scale trial that compared the effects of this agent with placebo and the twice-daily formulation (27). In this study, the median number of urge incontinence episodes in patients receiving the once-daily formulation, the twice-daily formulation, and placebo were reduced by 71%, 60%, and 33% respectively. Both preparations were statistically superior to placebo, and the once-daily was statistically more effective than the twice-daily using this outcome indicator. Statistically significant improvement in all other micturition diary variables was recorded for both formulations over placebo. The incidence of dry mouth was 23% for oncedaily tolterodine, 30% for twice-daily tolterodine, and 8% for placebo. 4.

Trospium Chloride

This is a quaternary ammonium non-receptor-selective antimuscarinic with low biologic availability (19) and with minimal CNS penetration (28). In one study, trospium was as effective

Pharmacologic Management of Incontinence


as oxybutynin in patients with hyperreflexia due to spinal cord injury, but had fewer adverse effects (29). Summarized data from published and unpublished RCTs showed an average of 43% (range 33 –54%) of 113 patients reported systemic anticholinergic side effects, described as “generally mild” (29). This agent is currently undergoing trials in the United States. 5.


Darifenacin is a highly selective M3 receptor antagonist with selectivity in some animal models for the urinary bladder over the salivary gland (30), but the clinical importance of this finding has not been established (7). In a small placebo-controlled study, published only in abstract form, a single 10-mg dose showed improvement in urodynamic parameters in patients with overactive bladder, although significant reductions in salivary flow were also apparent (31). No effects on salivation occurred at a dose of 2.5 mg, but this dose was no more effective than placebo as measured by urodynamic parameters. In a randomized, double-blind trial of 25 patients with detrusor instability, the effects of darifenacin 15 mg and 30 mg OD and oxybutynin 5 mg TID on ambulatory urodynamic monitoring and salivary flow were compared (32). The two drugs had similar urodynamic efficacy, but oxybutynin reduced salivary flow significantly more than darifenacin. Darifenacin is currently in Phase III evaluation in the United States and elsewhere. B.

Anticholinergic Agents with “Mixed” Actions

In addition to their antimuscarinic properties, this group of drugs induce multiple in vitro actions, including an independent “musculotropic” or “antispasmodic” action directly on smooth muscle. This effect occurs at a site that is metabolically distal to the cholinergic or other contractile receptor mechanism and is possibly related to calcium channel blockade. These drugs may also possess some local anesthetic properties, which, like the direct musculotropic relaxant effects, may only be relevant when given intravesically. When administered orally, the clinical relevance of these actions as compared to their well-recognized antimuscarinic properties is unclear, as these other effects only become apparent at much higher concentrations than their antimuscarinic actions (11,15). Thus their clinical effects when administered orally, likely occur solely through muscarinic blockade. If, however, any of these agents exerted a clinically significant direct inhibitory effect independent of their antimuscarinic action, there would be a therapeutic rationale for combination therapy with a relatively pure anticholinergic agent. 1. Oxybutynin Chloride This agent is a potent muscarinic receptor antagonist, with some degree of selectivity for M3 and M1 receptors. In human tissues, it has a higher affinity for muscarinic receptors in the parotid gland than it does for those in the bladder (15). Oxybutynin was originally developed to treat gastrointestinal hypermotility disorders. In vitro, its direct, smooth muscle relaxant effects are 500 times weaker than its antimuscarinic effects (11). This agent is a well-absorbed tertiary amine that undergoes an extensive first-pass (liver) metabolism (19). The pharmacologic properties of its active metabolite (N-desethyl oxybutynin) are similar to those of the parent compound, but the active metabolite occurs at concentrations six times higher. The major metabolite is also thought to cause the majority of adverse effects seen with this agent. Reducing the extent of first-pass metabolism by intravesical administration, GI absorption outside the portal system, transdermal, or rectal administration are potential avenues to improve tolerability. Initial reports documented the agent’s success in depressing detrusor overactivity in patients with neurogenic bladder dysfunction; subsequent reports have documented its success


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in inhibiting other types of bladder hyperactivity as well (10). Oxybutynin’s side effects are antimuscarinic and are dose related. An additional theoretical consideration is its physiochemical composition that might permit relatively greater penetration into the CNS through the blood-brain barrier. This may account for some of the reports of adverse CNS effects seen with this agent, especially in the geriatric population (33,34). The recommended oral adult dose of the immediate release formulation is 5 mg three or four times daily. The AHCPR Urinary Incontinence Guideline Panel reviewed six randomized clinical trials (RCTs); 90% of the patients were female (18). Reports of cure ranged from 28% to 44%, reductions in urge incontinence from 9% to 56%, side effects from 2% to 66%, and dropouts from 3% to 45%. In a review of 15 RCTs of 476 patients treated with oxybutynin, Thu¨roff et al. (19) reported a mean decrease in incontinence of 52% and a mean reduction in frequency of micturitions for 24 hours of 33%. The overall “subjective improvement” rate was 74% (range 61 –100%). Side effects were reported by a mean of 70% (range 17 –93%) of patients. Once-daily formulations of oxybutynin have been developed. Oxybutynin ER or XL uses an innovative osmotic drug delivery system to release the drug at a controlled rate over 24 h. This formulation overcomes the marked peak-to-trough fluctuations in plasma levels of both the drug and its major metabolite, which occurs with immediate-release oxybutynin (35). A trend toward a lower incidence of dry mouth with XL was attributed to reduced first pass metabolism and to the maintenance of lower and less-fluctuating plasma levels of drugs. Clinical trials on XL have concentrated primarily on comparing this drug with immediate-release oxybutynin. Anderson et al. reported on a multicenter, randomized, double-blind study on 105 patients with urge incontinence, or mixed incontinence with a clinically significant urge component. All had been prior positive responders to IR oxybutynin (36). Urge urinary incontinence episodes were the primary efficacy parameter. The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after XL and from 23.4 to 3.1 after IR oxybutynin, and total incontinence episodes decreased from a mean of 29.3 to 6 and from 26.3 to 3.8, respectively. Since only patients who had previously responded to treatment with oxybutynin were selected for treatment, these figures are not likely representative of what can be expected in clinical practice in an untreated, naive patient population. Dry mouth of any severity was reported by 68% and 87% of the controlled and immediate-release groups, respectively, and moderate or severe dry mouth occurred in 25% and 46%, respectively. Curiously, as voiding frequency was measured in both groups, a statistically greater percent increase was seen in the XL patients (54%) than in the IR patients (17%). The reason for the increase in urinary frequency seen in this study is unclear and is at odds with nearly all other antimuscarinic studies in which urinary frequency was measured as an outcome parameter. Another controlled study comparing efficacy and safety of controlled-release oxybutynin with conventional immediate-release oxybutynin included 226 patients with urge incontinence (37). They were known to respond to anticholinergic therapy and had seven or more urge incontinence episodes per week. Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the XL and IR oxybutynin groups (difference nonsignificant), respectively. The incidence of dry mouth increased with dose in both groups, but there was no statistically significant difference in dry mouth rates between the groups: 47.7% and 59.1% for the XL and IR, respectively. However, a significantly lower proportion of patients taking XL had moderate to severe dry mouth or any dry mouth compared with those taking IR oxybutynin. Other administration forms of oxybutynin have been introduced. Rectal administration (38,39) was reported to have fewer adverse effects than the conventional tablets, as was a transdermal preparation (40). Intravesical administration has also been successful in reducing systemic adverse effects while maintaining clinical improvement (41,42).

Pharmacologic Management of Incontinence



Comparing Oxybutynin and Tolterodine

A comparison of the efficacy and tolerability profiles of the two once-daily preparations would be of interest. To date, however, there have been no reported head-to-head studies, and inferences from existing studies are complicated by differences in enrolled patient populations and methodologies. Both tolterodine IR and oxybutynin XL have been compared to oxybutynin IR. Oxybutynin XL was shown to have equivalent efficacy to IR. Tolterodine IR and oxybutynin IR have also demonstrated equivalent efficacy. Tolterodine LA has not yet been directly compared to any of the oxybutynin formulations in a clinical study, but has been shown to be 18% more effective than tolterodine IR using median episodes of urge incontinence as an outcome indicator (27). One study has been completed that compared oxybutynin XL with tolterodine IR (43). Of 378 patients enrolled, 332 completed the 12-week study. Compared to baseline, weekly urge incontinence episodes per week were reduced (25.6 to 6.1 vs. 24.1 to 7.8, oxybutynin XL and tolterodine IR groups, respectively) as was urinary frequency (91.8 to 67.1 vs. 91.6 to 71.5 episodes per week). Although there was a statistically significant difference between the two drugs favoring oxybutynin in both of these outcome parameters, the overall clinical significance of these differences (e.g., a difference of 1.7 urge incontinent episodes per week) is unclear. Furthermore, like other oxybutynin XL controlled studies (36,37,43,44), there are some potential issues regarding the study design. Results were analyzed on a completer basis, which assesses the response rate in only those patients who completed the study. Secondly, statistical methods employed for analysis of the final data employed parametric analysis when the assumption of a normal distribution was unclear. Notably, however, adverse events including overall dry mouth (28.1% vs. 33.2% for oxybutynin XL vs. tolterodine IR, respectively) and constipation (7% vs. 6.2%, respectively) were not significantly different between the two groups. One small pharmacological study has been conducted which compared once daily tolterodine and oxybutynin (45). A double-blind, randomized, four-way crossover study compared oxybutynin XL 15 and 25 mg versus tolterodine LA 6 mg. XL treatment resulted in a linear dose-dependent increase in bladder capacity and a linear dose-dependent decrease in salivation. By extrapolation, LA 6 mg had the same effect on bladder capacity as a 20-mg dose of XL and the same effect on salivation as a 10-mg dosage. 3.

Dicyclomine Hydrochloride

This agent is reported to possess a direct relaxant effect on smooth muscle in addition to an antimuscarinic action. However, it is not widely used to treat OAB. The International Consultation on Incontinence (Committee on Pharmacology) (7) rated this drug as effective based on pharmacologic and physiologic evidence, but clinical evidence from good-quality randomized control trials was lacking (15). The ICI failed to recommend dicyclomine for use. 4.

Flavoxate Hydrochloride

This compound was originally thought to be a weak anticholinergic agent but, in addition, to possess a direct inhibitory action. Andersson and colleagues (7) cite references showing it has no anticholinergic effect but does have moderate calcium antagonist activity, local anesthetic properties, and the ability to inhibit phosphodiesterase (15). Overall, favorable clinical effects have been reported in some series of patients with frequency, urgency, and incontinence and in patients with urodynamically documented detrusor hyperreflexia (46). However, Briggs and colleagues reported essentially no effect on neurogenic detrusor overactivity in an elderly population (47). A similar conclusion was reached by Chapple and associates in a double-blind,


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placebo controlled, crossover study of idiopathic detrusor overactivity (48). Reported side effects are few. The drug failed to achieve a “recommended” assessment by the ICI, which noted that cogent evidence of pharmacologic or physiologic efficacy (or both) was lacking for this agent as well as evidence for its efficacy from good quality randomized controlled trials (48).


Potassium Channel Openers

These agents efficiently relax various types of smooth muscle (including detrusor smooth muscle) by increasing potassium efflux, which results in membrane hyperpolarization. This hyperpolarization reduces the probability that ion channels (primarily calcium) involved in membrane depolarization will open, with subsequent relaxation or inhibition of contraction (7,49). Potassium channel openers reduce spontaneous contractions as well as contractions induced by carbachol and electrical stimulation. Pinacidil and cromakalim, first-generation adenosine triphosphate (ATP)-sensitive potassium channel openers, have been used clinically. Evidence from preliminary trials did not support further efforts to pursue these drugs as treatment for detrusor overactivity (50,51), perhaps because they were found to be up to 200 times more potent as inhibitors of vascular smooth muscle preparations than detrusor muscle (7). However, attempts continue to develop a bladder-selective potassium channel opener.


Calcium Antagonists

The role of calcium as a messenger in linking extracellular stimuli to the intracellular environment is well established, including its involvement in excitation-contraction coupling in striated, cardiac, and smooth muscle (7,49,52). The dependence of contractile activity on changes in cytosolic calcium varies from tissue to tissue, as do the characteristics of the calcium channels involved. However, interference with calcium inflow or intracellular release is potentially a very potent mechanism for inducing bladder smooth muscle relaxation. These results have prompted support for the view that combined muscarinic receptor and calcium channel blockade might offer a more effective way to treat bladder overactivity than using either type of agent alone. Andersson conclude that available information does not currently support the use of oral calcium antagonists as an effective treatment for detrusor overactivity (49). A bladder-specific membrane calcium channel is not known to exist, and no agent blocks intracellular calcium release only in bladder smooth muscle cells. Intravesical therapy could theoretically prove useful, however.


Prostaglandin Antagonists

Prostaglandins are ubiquitous compounds that may potentially have a role in excitatory neurotransmission to the bladder, in the development of bladder contractility or tension occurring during filling, in the emptying contractile response of bladder smooth muscle to neural stimulation, and even in the maintenance of urethral tone during the storage phase of micturition, as well as in the release of this tone during the emptying phase (52 –54). Multiple mechanisms exist whereby prostaglandin synthesis inhibitors might decrease bladder contractility in response to various stimuli. However, no compelling clinical evidence supports their use in the treatment of detrusor overactivity (52).

Pharmacologic Management of Incontinence



b-Adrenergic Agonists

Because b-adrenergic receptors are present in human bladder muscle, researchers have attempted to increase bladder capacity with b-adrenergic stimulation. Such stimulation can cause significant increases in the capacity of animal bladders, which contain a moderate density of b-adrenergic receptors (54,55). However, the International Consultation on Incontinence Committee on Pharmacology did not recommend this group of agents because there was no evidence of clinical effectiveness (54). Recently, a b3-adrenergic receptor was identified and was shown to exist in human detrusor smooth muscle (56,57). The presence of this receptor may explain the b-adrenergic responses of detrusor muscle heretofore labeled atypical. Work is ongoing in this area.


a-Adrenergic Antagonists

At first glance, there seems to be no role for a-adrenergic antagonists to decrease detrusor contractility or increase bladder capacity since these have minimal, of any, contractile effects on human detrusor smooth muscle from normal individuals (7). However, the peripheral contribution of such receptors to bladder overactivity can change in neurologic disease or injury and as a result of bladder outlet obstruction or other causes. It is also possible that certain excitatory aspects of the micturition reflex may involve central a1-adrenergic receptors (49). a-Adrenergic blocking agents have been used to treat bladder and outlet abnormalities in patients with so-called autonomous bladders (58). These include voiding dysfunction resulting from myelodysplasia, sacral spinal cord or infrasacral neural injury, and radical pelvic surgery. Decreased bladder compliance is often a clinical problem in such patients, and this, along with a fixed urethral sphincter tone, results in the paradoxical occurrence of both storage and emptying failure. Norlen summarized the evidence for the success of a-adrenolytic treatment in these patients (58). Most would agree that the success has been moderate at best. Whether the effects on detrusor overactivity are central or peripheral (or both) have yet to be definitively to be definitively settled.


Tricyclic Antidepressants

Many clinicians believe that tricyclic antidepressants (particularly imipramine hydrochloride) are useful agents for facilitating urine storage because they decrease bladder contractility and increase outlet resistance (59). These agents have been the subject of numerous pharmacologic investigations to determine the mechanisms of action responsible for their varied effects (60,61). Most data are from attempts to explain the antidepressant properties of these agents and therefore are primarily from CNS tissue. The results, conclusions, and speculations inferred from the data are extremely interesting, but it is unknown whether they have relevance for the lower urinary tract. All of these agents possess varying degrees of at least three major pharmacologic actions: they have central and peripheral anticholinergic effects at some, but not all, sites; they block the active transport system in the presynaptic nerve ending, which is responsible for the reuptake of the released amine neurotransmitters norepinephrine and serotonin; and they are sedatives, an action that occurs presumably on a central basis, but may be related to antihistaminic properties. Imipramine and doxepin are the most commonly prescribed tricyclics for detrusor overactivity; data on their efficacy and tolerability for this indication are reviewed below.



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While this agent has prominent systemic anticholinergic effects, it has only A weak antimuscarinic effect on bladder smooth muscle (62). It does, however, exert a strong direct inhibitory effect—which is neither anticholinergic nor adrenergic—on bladder smooth muscle (63,64). The exact mechanism by which imipramine inhibits bladder activity is unknown. Recently, it has been postulated that these effects may be due to increased serotonin activity (due to reuptake blockade) in the central nervous system. This may involve a direct inhibition of normal excitatory pathways or a depression of afferent ascending neural activity (49,65). Clinically, imipramine has been shown to be effective in decreasing bladder contractility and in increasing outlet resistance (66,67). The AHCPR combined results for imipramine and doxepin, citing only three randomized clinical trials and an unknown percentage of female patients (18). Percent cures were listed as 31%, percent reduction in urge incontinence as 20– 77%, and percent side effects as 0 –70%. Our usual daily adult dosage for voiding dysfunction is 25 –75 mg once daily (possible because of the drug’s long half-life). We begin with the lowest dose and increase it by 25-mg increments every 7– 10 days if necessary, exercising extra caution in the elderly with respect to any dose .50 mg. In our own experience, the effects of imipramine on the lower urinary tract are often additive to those of the atropinelike agents. Consequently, combining imipramine with an antimuscarinic or an antispasmodic is sometimes especially useful for decreasing bladder contractility. When imipramine is used in conjunction with an atropinelike agent, the anticholinergic side effects of the drugs may also be additive. When used in the larger doses employed for antidepressant effect, the most frequent side effects of imipramine are anticholinergic. However, though uncommon, serious other side effects can occur, including CNS effects, postural hypotension, cardiac toxicity, weakness, and fatigue (60,61). Consultation with the internist or cardiologist is always helpful in questionable situations. Use is definitely contraindicated in patients receiving monamine oxidase inhibitors. All those contemplating the use of imipramine or other tricyclics (doxepin, e.g.) should be thoroughly familiar with the potential side effects and relative precautions. I.

Decreasing Sensory Input

Decreasing afferent input would be an ideal treatment for sensory disorders and for overactivity in a bladder with relatively normal elastic and viscoelastic properties in which the sensory afferents constitute the first limb in an abnormal micturition reflex. Maggi has written extensively about this type of treatment, specifically with reference to the properties of capsaicin (68,69). Capsaicin An irritant and algesiogenic compound obtained from hot red peppers, capsaicin has highly selective effects on a subset of mammalian sensory neurons, including polymodal receptors and warm thermoreceptors (70). It activates polymodal nociceptive neurons by opening a cationselective ion channel, allowing an influx of calcium and sodium ions that depolarize neuronal pain fibers (71,72). This ion channel is known as vanilloid-receptor subtype 1 (VR1). Repeated administration of capsaicin desensitizes and inactivates sensory neurons by several mechanisms. Systemic and topical capsaicin produces a reversible antinociceptive and anti-inflammatory action after an initially undesirable algesic effect. Local or topical application blocks C-fiber conduction and inactivates neuropeptide release from peripheral nerve endings, accounting for local antinociception and reduction of neurogenic inflammation. With local administration

Pharmacologic Management of Incontinence


(intravesical), the obvious potential advantage of capsaicin is a lack of systemic side effects. The actions are highly specific when the drug is applied locally, the compound affects primarily small-diameter nociceptive afferents, leaving the sensations of touch and pressure unchanged, although heat (not cold) perception may be reduced. Motor fibers are not affected. The effects are reversible, although it is not known whether initial levels of sensitivity are regained. DeRidder and Baert, in an excellent review article (73), summarized trials to that date as detailed by DeSeze and colleagues (74). Eighty-four percent had “some improvement” in their symptoms. The largest single series had been reported by DeRidder et al. (75); of 49 patients with multiple sclerosis, in 27% results were termed excellent, and in 55%, improved. DeRidder and Baert (73) also cite double blind trials using either placebo or the vehicle (30% ethanol in saline), showing clearly that it is indeed the capsaicin that produces the positive result.

2. Resiniferatoxin (RTX) This is the principal active ingredient in the drug euphorbium, the air-dried latex of the cactuslike plant Euphorbia resinifera, which is chemically related to the phorbol esters (73,76). RTX is likewise a vanilloid, and is, in fact, an ultrapotent (1000X) analog of capsaicin, but with minimal initial excitatory effect. RTX may induce desensitization in concentrations that are so low that no noxious effects are elicited (76). A summary of trials with resiniferatoxin is reported by DeRitter and Baert (73). These trials used concentrations ranging anywhere from 0.01 mmol/L to 1 mmol/ L, dissolved in either 10% ethanol or saline. The largest open study comprised 27 patients with multiple sclerosis and involuntary bladder contractions. A concentration of 0.5 –1 mmol/L in 10% ethanol was used. Twenty-one of 27 patients responded positively, mean bladder capacity increasing after 1 month from 208 to 467 mL and the mean urine loss for 24 h decreasing from 163 to 23 mL. Further randomized placebo controlled studies are ongoing. Neither capsaicin nor RTX is approved for clinical use in the United States. However, the intravesical use of such agents has the potential to significantly contribute to the treatment of bladder overactivity in patients with neurogenic and other types of lower urinary tract dysfunction. Theoretically, activities affected by these agents should include only those subserved by small unmyelinated afferent C fibers. A micturition reflex stimulated via myelinated Ad afferent fibers should not, theoretically, be affected by capsaicinlike agents.




a-Adrenergic Agonists

The bladder neck and proximal urethra contain a preponderance of a1-receptor sites, which, when stimulated, produce smooth muscle contraction. The static infusion urethral pressure profile is altered by such stimulation, which produces an increase in maximum urethral pressure (MUP) and maximum urethral closure pressure (MUCP). Various orally administered pharmacologic agents are available that produce a-adrenergic stimulation. Generally, outlet resistance is increased to a variable degree by such an action. Potential side effects of all of these agents include blood pressure elevation, anxiety, and insomnia from stimulation of the CNS; headache; tremor; weakness; palpitations; cardiac arrhythmias; and respiratory difficulties. They should be used with caution in patients with hypertension, cardiovascular disease, or hyperthyroidism (5).



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Ephedrine, Pseudoephedrine

Ephedrine is a noncatecholamine sympathomimetic agent that enhances release of norepinephrine from sympathetic neurons and directly stimulates both a- and b-adrenergic receptors. The oral adult dosage is 25– 50 mg QID. Some tachyphylaxis develops to its peripheral actions, probably as a result of depletion of norepinephrine stores. Pseudoephedrine, a stereoisomer of ephedrine, is used for similar indications with similar precautions. The adult dosage is 30– 60 mg QID, and the 30-mg dose form is available in the United States without prescription (Sudafed, others). Diokno and Taub (77) reported a “good to excellent” result in 27 of 38 patients with sphincteric incontinence treated with ephedrine sulfate. Beneficial effects were most often achieved in those with minimal to moderate wetting, and little benefit was achieved in patients with severe stress incontinence. In past years similar results had been reported in the literature with the use of these agents; however, in retrospect, these results are somewhat inconsistent with current opinion and show the value of accurate objective outcome indicators and double-blind placebo-controlled studies.


Phenylpropanolamine (PPA)

PPA has classically been reported to share the pharmacologic properties of ephedrine and be approximately equal in peripheral potency while causing less central stimulation. It is available in 25- and 50-mg tablets and 75-mg time-release capsules and is a component of numerous proprietary mixtures, some marketed for the treatment of nasal and sinus congestion (usually in combination with an H1 antihistamine) and some marketed as appetite suppressants. Using doses of 50 mg TID, Awad and associates (78) claimed that 11 of 13 females and 6 of 7 males with stress incontinence were significantly improved after 4 weeks of therapy. MUCP increased from a mean of 47 cmH2O to 72 cmH2O in patients with an empty bladder and from 43 cmH2O to 58 cmH2O in patients with a full bladder. Using a capsule (Ornade) that then contained 50 mg of PPA, 8 mg of chlorpheniramine (an antihistamine), and 2 mg of isopropamide (an antimuscarinic), Stewart and associates (79) reported that, of 77 women with stress urinary incontinence, 18 were completely cured with one sustained release capsule taken BID. Twentyeight patients were “much better,” six were “slightly better,” and 25 were no better. In 11 men with postprostatectomy stress incontinence, the numbers in the corresponding categories were 1, 2, 1, and 7. The formulation of Ornade has now been changed, and each capsule of drug contains 75 mg PPA and 12 mg chlorpheniramine. The AHCPR Guideline (18) reports eight randomized controlled trials with PPA, 50 mg BID, for stress urinary incontinence in females. Percent cures (all figures refer to percent effect on drug minus percent effect on placebo) are listed as 0 – 14, percent reduction in incontinence as 19 –60, and percent side effects and percent dropouts as 5– 33 and 0 – 4.3, respectively. There are potential complications of PPA, especially hypertension. Most recently the FDA has asked manufacturers to voluntarily stop selling PPA-containing drugs and replace the ingredient with a safer alternative (80). This request, which, it was hinted, may be replaced by a ban, was based on a study reported by Kernan and coworkers (81) in the New England Journal of Medicine. They compared 702 adults younger than 50 years old with subarachnoid or intracerebral hemorrhage to 1376 controls, reporting the risk of hemorrhagic stroke to be 16 times higher in women who had been taking PPA as an appetite suppressant and three times higher in women who had taken the drug for ,24 h as a cold remedy. This last finding was not statistically significant. PPA was reported not to be associated with an increased risk of stroke in men. In commenting on this article, Abramowicz and Zuccotti (82) writing in the Medical Letter, noted that no case control studies were available on the safety of phenylephrine,

Pharmacologic Management of Incontinence


ephedrine, or pseudoephedrine but did relate that case reports have associated ephedra alkaloids with hypertension, stroke, seizures, and death. Their article concluded, “Phenylpropanolamine may not be the only alpha-adrenergic agonist that can cause serious adverse effects when taken systemically in over-the-counter products marketed for nasal congestion or weight loss.” Thus, extreme caution must be exercised in choosing patients, especially women, for a-adrenergic agonist therapy. We currently do not recommend this. D.

Imipramine; Duloxetine

The actions of imipramine have already been discussed in the section on inhibiting bladder contractility. On a theoretical basis, an increase in urethral resistance might be expected if indeed an enhanced a-adrenergic effect is produced at this level because of an inhibition of norepinephrine reuptake. Many clinicians have noted improvement in patients who were treated with imipramine primarily for reasons related to bladder hyperactivity, but who had, in addition, some component of sphincteric incontinence. Gilja and coworkers (83) reported a study of 30 women with stress incontinence treated with 75 mg imipramine daily for 4 weeks. Twentyone women subjectively reported continence. Mean MUCP for the group increased from 34.06 mmHg to 48.23 mmHg. In an open study Lin and colleagues (84) reported that 25 mg imipramine TID for 3 months resulted in a 35% cure rate by pad test in 40 women with stress incontinence. In an additional 25%, there was a 50% or more improvement. Success seemed to correlate with a higher urethral closure pressure. Duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, under conditions of “bladder irritation,” enhances external urethral sphincter activity in the cat through serotonergic and a1-adrenergic mechanisms, probably at a central level. It also produces a centrally mediated increase in bladder capacity through a serotonergic mechanism (85). Duloxetine is currently undergoing clinical trials in the United States. E.


Although some clinicians have reported spectacular cure and improvement rates with a-adrenergic agonists and agents that produce an a-adrenergic effect in the outlet of patients with sphincteric urinary incontinence, our own experience coincides with those who report that treatment with such agents often produces satisfactory or some improvement in mild cases, but rarely total dryness in cases of severe or even moderate stress incontinence. Such therapy, when utilized, should always be employed in conjunction with pelvic floor physiotherapy/ biofeedback to achieve optimal results.



In the postmenopausal female, on a statistical basis, the prevalence of lower urinary tract symptoms, including incontinence, and urinary tract infection are increased. Estrogen levels have obviously declined. The question is whether these phenomena are causally related. If so, estrogen supplementation would be a rational therapy for incontinence. The role of estrogen therapy in the treatment of bladder overactivity and stress incontinence has remained controversial. Unfortunately, most reported studies are observational and not randomized, blinded, or controlled. The situation is further complicated by the fact that a number of different types of estrogen have been used with varying doses, routes of administration, and treatment duration—some with progestational agents and some without. Some authorities even seem to


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advocate opposite positions on this question in different articles. If estrogen has a role in treating LUTS in the postmenopausal female, it is most likely through one or more of the following mechanisms: (a) raising the sensory threshold of the bladder and/or urethra; (b) increasing the a-adrenoceptor sensitivity in urethral smooth muscle; (c) increasing urethral resistance by (b) or by another mechanism; (d) correcting underlying urogenital atrophy. Both Hextall (86) and Andersson (28) have carefully reviewed the relevant literature on this subject and offered what we feel are valid summaries. Our inferences from their reports regarding the success of estrogen usage in the treatment of various LUTS in the postmenopausal female is as follows: stress incontinence—probably not; urge incontinence—probably not; urgency and frequency—maybe; urinary tract infections—yes, especially with a vagin*l preparation.



4. 5. 6. 7. 8. 9. 10. 11. 12.

13. 14. 15. 16. 17.

Wein AJ. Pharmacological agents for the treatment of urinary incontinence due to overactive bladder. Invest Drugs 2001; 10:65 – 83. Rovner ES, Wein AJ. Pharmacologic treatment for non-BPH induced voiding dysfunction: facilitation of bladder emptying, Part I. AUA Update Series. AUA Update Series 17. Houston, TX: American Urological Association, 1998:258 – 265. Rovner ES, Wein AJ. Pharmacologic treatment for non-BPH induced voiding dysfunction: facilitation of urine storage, Part II. AUA Update Series. AUA Update Series 17. Houston, TX: American Urological Association, 1998:266 – 272. Wein AJ, Rovner ES. Pharmacologic management of the overactive bladder. Contem Urol 2001; 6:22– 35. Wein AJ. Neuromuscular dysfunction of the lower urinary tract and its management. In: Walsh PC, Retik A, Vaughan ED Jr, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 2002. Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Walsh PC, Retik A, Vaughan ED Jr, eds. Campbell’s Urology. Philadelphia: W.B. Saunders, 2002. Andersson K-E, Appell R, Cardozo L. Pharmacological treatment of urinary incontinence. In: Abrams P, Khoury S, Wein AJ, eds. Incontinence. Plymouth, UK: Heath Publication, 1999:447– 486. Andersson K-E, Appell R, Cardozo L. The pharmacological treatment of urinary incontinence. BJU Int 1999; 84:923 – 947. Andersson K-E. The concept of uroselectivity. Eur Urol 1998; 33:7 –11. Andersson K-E. Current concepts in the treatment of disorders of micturition. Drugs 1988; 35:477– 494. Andersson K-E. Advances in the pharmacological control of the bladder. Exp Physiol 1999; 84:195– 213. Jensen D Jr. Pharmacological studies of the uninhibited neurogenic bladder. II. The influence of cholinergic excitatory and inhibitory drugs on the cystometrogram of neurological patients with normal and uninhibited neurogenic bladder. Acta Neurol Scand 1981; 64:175 – 195. Andersson K-E. Changes in bladder tone during filling: pharmacological aspsects. Scand J Urol Nephrol 1999; 201:67 – 72; Discussion 76 – 99. Caulfield MP, Birdsall NJ. International union of pharmacology XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 1998; 50:279 –290. Chapple C. Muscarinic receptor antagonists in the treatment of overactive bladder. Urology 2000; 55(suppl 5A):33– 46. Braverman A, Legos J, Young W. M2 receptors in genitourinary smooth muscle pathology. Life Sci 1999; 64:432. Braverman AS, Ruggieri MR, Pontari MA. The M2 muscarinic receptor subtype mediates cholinergic bladder contractions in patients with neurogenic bladder dysfunction. J Urol 2001; 165:36.

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27. 28. 29. 30. 31.


33. 34. 35. 36. 37. 38. 39. 40.



Agency for Health Care Policy and Research: Urinary Incontinence Guideline Panel. Urinary Incontinence in Adults: Clinical Practice Guidelines (AHCPR publication #92-0038). Rockville, MD: Public Health Service, U.S. Department of Health & Human Services, 1992. Thu¨roff J, Abrams P, Chartier-Kasher E. Medical treatment and medical side effects in urinary incontinence in the elderly. World J Urol 1998; 16:548 –561. Nilvebrant L, Sundquist S, Gilberg PG. Tolterodine is not subtype (M1 –M5) selective but exhibits functional bladder selectivity in vivo. Neurourol Urodyn 1996; 15:310 – 311. Nilvebrant L, Andersson K-E, Gilberg PG. Tolterodine—a new bladder-selective antimuscarinic agent. Eur J Pharmacol 1997; 327:195 – 207. Stahl MM, Ekstrom B, Sparf B. Urodynamic and other effects of tolterodine: a novel antimuscarinic drug for the treatment of detrusor overactivity. Neurourol Urodyn 1995; 14:647– 655. Appell R. Clinical efficacy and safety of tolterodine in the treatment of ovracrtive bladder: a pooled analysis. Urology 1997; 50:90 –99. Chancellor M, Freedman S. Tolterodine, an effective and well tolerated treatment for urge incontinence and other overactive bladder symptoms. Clin Drug Invest 2000; 19:83 – 91. VanKerrebroeck PH, Serment G, Deker E. Clinical efficacy and safety of tolterodine. Neurourol Urodyn 1997; 16:478 –479. Drutz HP, Appell RA, Gleason D. Clinical efficacy and safety of tolterodine compared to oxybutynin and placebo in patients with overactive bladder. Int Urogynecol J Pelvic Floor Dysfunc 1999; 10:283– 289. VanKerrebroeck PH, Kreder KJU. Tolterodine—once daily: superior efficacy and tolerability in the treatment of the overactive bladder. Urology 2001; 57:414– 421. Andersson K-E, Appell R, Awad S. Pharmacological treatment of urinary incontinence, in Abrams P, Khoury S, Cardozo L. eds. Incontinence. Plymouth, UK: Heath Publications, 2002. Madersbacher H, Sto¨hrer M, Richter R. Trospium chloride versus oxybutynin: a randomized double blind multicentre trial in the treatment of detrusor hyperreflexia. Br J Urol 1995; 75:452 – 456. Wallis RM, Napier CM. Muscarinic antagonists in development for disorders of smooth muscle function. Life Sci 1999; 64:395 – 401. Rosario DJ, Cutinha PR, Chapple CR. The effects of single dose darifenacin on cystometric parameters and salivary flow in patients with urge incontinence secondary to detrusor instability. Eur Urol 1996; 30:240. Mundy, AR, Abrams, P, Chapple, CR. Darifenacin, the first selective M3 antagonist for overactive bladder: comparison with oxybutynin on ambulatory urodynamic monitoring and salivary flow. International Continence Society, 2001. Katz IR, Sands LP, Bilker W. Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatric Soc 1998; 46:8– 12. Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, trospium chloride, and oxybutynin on the central nervous system. J Clin Pharmacol 2001; 41:636 – 641. Gupta SK, Sathyan G. Pharmaco*kinetics of an oral once a day controlled release oxybutynin formulation compared with immediate release oxybutynin. J Clin Pharmacol 1999; 39:289 – 296. Anderson RU, Mobley D, Blank B. Once daily controlled versus immediate release oxybutynin chloride for urge incontinence. J Urol 1999; 161:1809– 1814. Versi E, Appell R, Mobley D. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. Obstet Gynecol 2000; 95:18– 24. Collas D, Malone-Lee JG. The pharmaco*kinetic properties of rectal oxybutynin—a possible alternative to intravesical administration. Neurourol Urodyn 1997; 16:346 – 350. Winkler HA, Sand PK. Treatment of detrusor instability with oxybutynin rectal suppositories. Int Urogynecol J Pelvic Floor Dysfunc 1998; 9:100– 104. Davila GW, Daugherty CA, Sanders SW. A short term, multicenter, randomized, double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J Urol 2001; 166:140–145. Brendler CB, Radebaugh LC, Mohler JL. Topical oxybutynin chloride for relaxation of dysfunctional bladders. J Urol 1989; 141:1350– 1352.

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Wein and Rovner O’Flynn KJ, Thomas DG. Intravesical instillation of oxybutynin hydrochlorixe for detrusor hyperreflexia. Br J Urol 1993; 723:566 – 570. Appell RA, Sand P, Dmochowski R. Prospective randomized controlled trial of extended release oxybutynin chloride and tolterodine tartrate in the treatment of overactive bladder. Results of the OBJECT study. Mayo Clinic Proc 2001; 76:358– 363. Gleason DM, Susset J, White C. Evaluation of a once daily formulation of oxybutynin for the treatment of urinary urge incontinence. Ditropan XL Study Group. Urology 1999; 54:420– 423. Chapple C. Tolterodine once daily: selectivity for the bladder over effects on salivation compared to Ditropan XL. J Urol 2001; 165:253 – 257. Jonas U, Petri E, Kissel J. Effect of flavoxate on uninhibited detrusor muscle. Eur Urol 1979; 5:106– 109. Briggs RS, Castleden CM, Asher MJ. The effect of flavoxate on uninhibited detrusor contractions and urinary incontinence in the elderly. J Urol 1980; 123:665– 666. Chapple CR, Parkhouse H, Gardener C. Double-blind placebo controlled crossover study of flavoxate in the treatment of idiopathic detrusor instability. Br J Urol 1990; 66:491 – 494. Andersson K-E. Treatment of overactive bladder: other drug mechanisms. Urology 2000; 55:51 –57; Discussion 76 –99. Fovaeus M, Andersson K-E, Hedlung H. The action of pinacidil in the isolated human bladder. J Urol 1989; 141:637 –640. Nurse DE, Restorick JM, Mundy AR. The effect of cromakalin on the normal and hyperreflexic human detrusor muscle. Br J Urol 1991; 68:27 – 31. Andersson K-E. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 1993; 45:253– 308. Andersson K-E. Pathways for relaxation of detrusor smooth muscle. In: Baskin LL, Hayward SW, eds. Advances in Bladder Research. New York: Kluwer Academic/Plenum Publishers, 1999:241–252. Zderic SA, Levin RM, Wein AJ. Voiding function: relevant anatomy, physiology, pharmacology, and molecular aspects. In: Gillenwater J, Grayhack J, Howards S, et al eds. Adult and Pediatric Urology. Chicago: Mosby-Year Book, 1995:1159 – 1219. Levin RM, Wein AJ. Quantitative analysis of alpha and beta adrenergic receptor densities in the lower urinary tract of the dog and the rabbit. Invest Urol 1979; 17:75 – 77. Igawa Y, Yamazaki Y, Takeda H. Functional and molecular biological evidence for a possible beta3adrenoceptor in the human detrusor muscle. Br J Pharmacol 1999; 126:819– 825. Takeda M, Obara K, Mizusawa T. Evidence for b3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J Pharmacol Exp Ther 1999; 288:1367 – 1373. Norlen L. Influence of the sympathetic nervous system on the lower urinary tract and its clinical implications. Neurourol Urodyn 1982; 1:129– 133. Wein AJ. Pharmacology of incontinence. Urol Clin North Am 1995; 22:557 –577. Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and mania. In: Hardman JG, Limbird LE, Molinoff PB, et al eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw-Hill Health Professions Division, 1996:431– 461 Richelson E. Pharmacology of antidepressants—characteristics of the ideal drug. Mayo Clin Proc 1994; 69:1069 –1081. Levin RM, Staskin DR, Wein AJ. Analysis of the anticholinergic and musculotropic effects of desmethylimipramine on the rabbit urinary bladder. Urol Res 1983; 11:259 – 262. Olubadewo J. The effect of imipramine on rat detrusor muscle contractility. Arch Int Pharmacodyn Ther 1980; 245:84 – 94. Levin RM, Wein AJ. Comparative effects of five tricyclic compounds on the rabbit uirnary bladder. Neurourol Urodyn 1984; 3:127 – 135. Espy MJ, Du HJ, Downie JW. Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats. Brain Res. 1998; 798:101– 108. Cole AT, Fried FA. Favorable experiences with imipramine in the treatment of neurogenic bladder. J Urol 1972; 107:44– 45.

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Castleden CM, George CF, Renwick AG. Imipramine—a possible alternative to current therapy for urinary incontinence in the elderly. J Urol 1981; 125:318– 320. Maggi CA, Barbanti G, Santicioli P. Cystometric evidence that capsaicin sensitive nerves modulate the afferent branch of micturition reflex in humans. J Urol 1989; 142:150 – 154. Maggi CA. Capsaicin and primary afferent neurons: from basic science to humantherapy? J Auton Nerv Syst 1993; 33:1– 14. Dray A. Mechanism of action of capsaicin-like molecules onsensory neurons. Life Sci 1992; 51:1759– 1765. Caterina JJ, Schumacher MA, Tominaga M. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389:816– 824. Caterina MJ, Rosen TA, Tominaga M. A capsaicin-receptor hom*ologue with a high threshold for noxious heat. Nature 1999; 398:436 – 441. DeRidder D, Baert L. Vanilloids and the overactive bladder. BJU Int 2000; 86:172– 180. DeSeze M, Wiart L, Ferriere J. Intravesical instillation of capsaicin in urology: a review of the literature. Eur Urol 1999; 36:267 – 277. DeRidder D, Chanderamini VA, Dasgupta P. Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long term follow up. J Urol 1997; 158:2087 – 2093. Chancellor MB, DeGroat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 1999; 162:3– 11. Diokno A, Taub M. Ephedrine in treatment of urinary incontinence. Urology 1975; 5:624 – 627. Awad S, Downie J, Kirutula J. Alpha adrenergic agents in urinary disorders of the proximal urethra: I. Stress incontinence. Brit J Urol 1978; 50:332– 336. Stewart B, Borowsky L, Montague D. Stress incontinence: conservative therapy with sympathomimetic drugs. J Urol 1976; 115:558 – 562. Neergaard L. An FDA warning on cold and diet drugs. Philadelphia Inquirer Nov. 7, 2000. Kernan WN, Viscoli CM, Brass LM. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000; 343:1932. Abramowicz M, Zuccotti G. Phenylpropanolamine and other OTC alpha-adrenergic agonists. Med Lett Drugs Ther 2000; 42:113. Gilja I, Radej M, Kovacic M. Conservative treatment of female stress incontinence with imipramine. J Urol 1984; 132:909– 914. Lin H-H, Sheu BC, Lo M-Cea. Comparison of treatment outcomes of imipramine for female genuine stress incontinence. Brit J Obstet Gynaecol 1999; 106:1089 – 1092. Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the choralose anesthetized female cat. J Pharmacol Exptl Therap 1995; 274:1024. Hextall A. Oestrogens and lower urinary tract functions. Maturitas 2000; 36:83 – 87.

14 Behavioral Treatments Diane K. Newman University of Pennsylvania Medical Center, Philadelphia, U.S.A



Behavior modification is an accepted treatment option for persons with urinary lower urinary tract symptoms (LUTS) which include urinary incontinence (UI) and overactive bladder (OAB), which include urgency, frequency, with or without urge UI and nocturia. These interventions improve symptoms through identification of lifestyle habits and changing a person’s behavior, environment or activity that are contributing factors or triggers (1). Interventions such as bladder retraining and pelvic floor muscle rehabilitation attempt to decrease incontinence and OAB symptoms through increasing awareness of the function and coordination of the bladder and pelvic floor muscle so as to gain muscle identification, control, and strength and to decrease bladder overactivity. These interventions are often referred to as behavioral treatments, and involve learning new skills through extensive one-on-one patient instruction on techniques for preventing urine loss, urgency, and other symptoms. These treatments have a growing body of clinical research. The Agency for Health Care Policy and Research (AHCPR) clinical practice guideline on urinary incontinence in adults recommended these treatments as first line interventions (2,3). AHCPR is now known as the Agency for Healthcare Research and Quality (AHRQ). These guidelines defined behavioral interventions as a group of therapies used to modify stress, urge, or mixed urinary incontinence by changing the person’s bladder habits or by teaching new skills. They have been defined to include lifestyle changes (e.g., cessation of smoking, weight reduction, elimination of dietary bladder irritants, adequate fluid intake, bowel regulation, moderation of physical activities, and exercises), toileting programs (e.g., habit training and prompted voiding), bladder training, pelvic floor muscle training or rehabilitation utilizing methods such as biofeedback, vagin*l weights, and pelvic muscle electrical stimulation. This chapter outlines the current research as well as clinical practice on the use of behavioral treatment, specifically lifestyle or self-care practices, scheduled toileting programs, bladder training and pelvic muscle rehabilitation. Despite the high level of evidence supporting the effectiveness of behavioral therapy, there are few demonstrations of outcomes obtained when this research is translated into clinical practice. A common complaint of behavioral treatments is that the outcome reflects the combination of these treatments as opposed to a single intervention. More research on clinical effectiveness is needed to encourage health care clinicians, specifically doctors and nurses, to incorporate behavioral therapy instruction into standard treatment care protocols. 233





In many instances, lifestyle practices can be the contributing cause of LUTS, especially in women. The following is the current summary of these practices. A.


Conditions exist in which increased intra-abdominal pressure may promote the development of UI and urinary urgency, particularly in women. These conditions include pulmonary diseases such as asthma, emphysema, and chronic coughing such as seen in persons who smoke. Smoking increases the risk of developing all forms of UI, and stress UI in particular, depending on the number of cigarettes smoked. There may be several causes of the increased risk of stress UI in smokers. Smokers have stronger, more frequent, and more violent coughing, which may lead to earlier development of anatomic and pressure damage of the urethral sphincteric mechanism and of vagin*l supports (4). Violent and frequent, prolonged coughing can increase downward pressure on the pelvic floor, causing repeated stretch injury to the pudendal and pelvic nerves. Smoking is also the most important etiological factor in bladder cancer. There is felt to be antiestrogenic hormonal effects of products found in tobacco products. These effects are felt to affect the production of collagen synthesis. Nicotine has been shown to contribute to large phasic bladder contractions in animal studies through the activation of purinergic receptors and has been postulated to similarly affect the human bladder (5,6). There may also be an association between nicotine and increased detrusor contractions. Bump and McClish (7) demonstrated that women who previously smoked had a 2.2-fold increase and those who currently smoked have a 2.5-fold increase in stress UI. One case control study of 80 incontinent and 80 continent women established a strong statistical relationship between cigarette smoking and urinary incontinence (8). Nuotio et al. (9) showed a correlation between smoking and urinary urgency in a population based survey of 1059 women and men aged 60– 89 years. A large cross-sectional study evaluated multiple risk factors for incontinence, including smoking in women attending antenatal care (10). Smokers were more likely to report incontinence than nonsmokers. The previous research was concentrated in women, but Koskimaki et al. (11) showed an increased risk of LUTS in a survey of 2128 middle-aged and elderly men who smoked currently or formerly. LUTS symptoms included incomplete bladder empting and hesitancy, daily frequency, nocturia, urgency, and urge incontinence. The effects of smoking on LUTS are probably mediated through the development of BPH. In men, tobacco products may increase accumulation of androgens in the prostate gland. The study also found that in men, the risk of LUTS decreased, disappearing 40 years after cessation of smoking. No data have been reported examining whether smoking cessation in women resolves incontinence. However, in clinical practice, women who smoke are educated on the relationship between smoking and UI, and strategies designed to discourage women from smoking are often suggested; however, no evidence supports their effectiveness (12). B.


Obesity has been identified as an independent risk factor for the development of stress and mixed UI in women (13 –16). Research looking at the relationship between obesity and incontinence used body mass index (BMI). A BMI of 29 is considered normal or low weight, and a BMI of 30 a high weight or obese. The stress UI seen in obesity may be secondary to increases in intraabdominal pressure on the bladder and greater urethral mobility. Also, obesity may impair blood flow or nerve innervation to the bladder. Elia et al. (13) reported on 540 women who responded

Behavioral Treatments


to a questionnaire of which BMI status was attained. The association between BMI and UI was statistically significant. Mommsen and Foldspang (16) reported on 2589 women in Denmark who responded to a mailed questionnaire. BMI was found to correlate with urge UI in women who reported having one or more episodes of cystitis. It was hypothesized that poor personal hygiene in obese women may lead to an infectious process. Mommsen also found a relationship between stress UI and an increased BMI. Dwyer et al. (17) found women with genuine stress UI or with detrusor instability to have a higher mean BMI than the general population of the same age. Roe and Doll (18) reported on 6139 (53% response rate) respondents to a British postal survey on incontinence status. Significantly more obese respondents have UI than continent respondents. This association was more prevalent in obese women than men. Brown et al. (19) studied 2763 women who completed questionnaires on prevalence and type of incontinence as part of a randomized trial of estrogen hormone therapy. A higher BMI and higher waist-to-hip ratio were found to be predictors of stress UI and also of mixed UI when the major component was stress. This study found that the prevalence of at least weekly stress UI increased by 10% per 5 units BMI. Højberg et al. (10) found that BMI . 30 and smoking were possible risk factors for women attending antenatal care who were 16 at weeks’ gestation. Weight loss is an acceptable treatment option for morbidly obese women. Research has shown that stress UI symptoms decrease in morbidly obese women who undergo extreme weight loss after gastric bypass surgery (20). At this time, there is little information on whether weight loss resolves incontinence in women who are moderately obese. Subak et al. (21,22) showed that improvement in UI was seen when participants lost as little as 5% from baseline weight so weight loss is recommended in clinical practice to all women who have a BMI . 30. Clinicians might suggest self-weight programs such as Weight Watchers or depending on the BMI refer the women to a physician-monitored weight loss program or possibly weight reduction surgery. C.

Dietary Habits

There are components of everyday diet and bodily functions that can “trigger” LUTS which if eliminated through modification can also decrease their effects. These components include amount of fluid intake; the ingestion of certain beverages, foods, and medications; and maintaining normal bowel regulation (23). 1.

Fluid Management

Individuals may subscribe to either a restrictive or excessive fluid intake behavior. Adequate fluid intake is needed to eliminate irritants from the bladder. Underhydration may play a role in the development of urinary tract infections (UTIs) and decreases the functional capacity of the bladder (24). Surveys of community-residing elders report self-care practices to include the selfimposed restrictions of fluids, as they fear UI, urinary urgency, and frequency (25,26). Adequate fluid intake is very important for older adults, who already have a decrease in their total body weight and are at increased risk for dehydration. However, the research showing the relationship of quantity of fluid intake to urinary symptoms is inconclusive. In a geriatric population, there appears to be a strong relationship between evening fluid intake, nocturia, and nocturnal voided volume (27). Nygaard and Linder (28) surveyed teachers and questioned their voiding habits at work, allotted breaks, bladder complaints including UTIs, and incontinence. Teachers who drank less while working to decrease their voiding frequency had a twofold higher risk of UTI than those who did not report self-imposed fluid restriction. There was no association between UTI and either voiding infrequently at work or the mean number of voids at work. Fitzgerald et al. (29) surveyed



women who worked for a large academic center. Of the 1113 women surveyed, 21% (n ¼ 232) reported UI at least monthly. Incontinent women were significantly older and had a higher BMI than continent women. One of the strategies women in this study used to avoid urinary symptoms was limiting fluids and avoiding caffeinated beverages. Wyman et al. (30) reported a positive relationship between fluid intake and severity of UI in women with stress UI over age 55 years. However, in this same study there was no correlation in women with detrusor instability. In a randomized trial, Dowd (31) assigned 32 women to one of three groups: group 1 increased fluid intake by 500 cc over baseline; group 2 decreased by same amount; and group 3 maintained baseline level. The authors reported that 20 women who had fewer incontinent episodes at the end of the trial attributed this to drinking more fluids. Women in this study noted that it was easier to limit daily intake than to increase it. The recommended daily fluid intake is 1500 mL, but many feel that a more appropriate intake is 1800 –2400 mL/d. To be adequately hydrated, it is felt that older patients must consume at least 1500 –2000 mL/d of liquids (32). Many patients, especially women who are dieting or who actively exercise, may drink excessive fluids that may total more than 4000 mL/d. If they are experiencing UI, they should be encouraged to decrease the amount. The timing of fluid may be important in persons who have problems with nocturia. Aging causes an increase in nocturia, defined as the number of voids recorded from the time the individual goes to bed with the intention of going to sleep, to the time the individual wakes with the intention of rising. Nocturia is an average of greater than 2 nocturnal voids per night. Nocturia can be diagnosed as nocturnal polyuria (NP), which causes the largest amount of urine production to occur at rest while the person is supine. Chronic medical conditions such as congestive heart failure, venous stasis with peripheral edema, hypoglycemia, excess urine output, obstructive sleep apnea, and diuretics as well as evening/nighttime fluid consumption are causes of NP. During the night, there is a lower level of physical activity, and body fluid moves more quickly from one part of the body to another, causing an increase in the amount of urine in the bladder. To decrease nocturia precipitated by drinking fluids primarily in the evening or with dinner, the person should be instructed to reduce fluid intake after 7 PM and shift intake toward the morning and afternoon. 2.

Influence of Bladder Irritants

The type of fluid or food is felt to be important (33). Caffeine is an ingredient found in certain beverages, foods, and medications and is felt to impact LUTS by causing a significant rise in detrusor pressure (34). Caffeine has been shown to have an excitatory effect on detrusor muscle contraction (35). The consumption of caffeinated beverages, foods, and medications should not be underestimated. In the United States, .80% of the adult population consumes caffeine in the form of coffee, tea, or soft drinks on a daily basis. It is estimated to average 200 mg d, which is equivalent to two 7.5-oz cups of brewed coffee (36). Additionally, the U.S. Food and Drug Administration (FDA) has listed .300 drugs that are bought off over the counter (OTC) in pharmacies and retail drug stores that contain caffeine. Caffeine is usually listed on the label of the products. In addition to caffeine, alcohol is also felt to have a diuretic effect that can lead to increased frequency. Alcohol causes a release of antidiuretic hormone (ADH) from the posterior pituitary (34). Alcohol with dinner may be a contributing factor for nocturia. Anecdotal evidence suggests that eliminating dietary factors such as artificial sweeteners (aspartame) and certain foods (e.g., highly spiced foods, citrus juices, and tomato-based products) may play a role in continence (37).

Behavioral Treatments


Research has shown that urine leakage decreased (63%) when caffeine consumption was reduced from 23 to 14 g (38). Arya et al. (39) found that women (N ¼ 20) with higher caffeine intake (484 + 123 mg/d) had a 2.4-fold increased risk for detrusor instability than women (N ¼ 10) with a low caffeine intake (194 + 84 mg/d). There was also a correlation between current smoking and caffeine intake. Bryant et al. (40) conducted a prospective randomized controlled trial of persons with symptoms of urgency, frequency, and urge UI who routinely ingested 100 mg or more of caffeine per day. Both groups were taught bladder training, but the intervention group was also instructed to reduce caffeine intake. Significant improvement in urine loss was seen in the intervention group. Results in this study appeared to affect the OAB symptom of urgency. A 37% reduction was found among low users (100 – 200 mg of caffeine), a 5% reduction was found among medium users (201 – 300 mg) and a 4% increase was found among the high users (.301 mg). Tomlinson et al. (38) showed in 34 women with symptoms of UI (mostly mixed) who decreased caffeine intake (from 900 mL/d to 480 mL/d), episodes of daily urine loss also decreased (from 2.33 to 1.0 mg/d). Even though current research is not conclusive, clinicians should assess all patients with LUTS for amount of daily caffeine intake. Patients should be advised about the possible adverse effects caffeine may have on the detrusor muscle and the possible benefits of reduction of caffeine intake (41). The patient should be instructed to switch to caffeine-free beverages and foods or eliminate them and see if symptoms decrease or resolve. Patient Guide #1 lists the caffeine intake of common products. Patients need to read product labels. Herbal teas that are felt to be more “natural” usually contain caffeine unless stated otherwise. Patients seem to think that iced tea has less caffeine than hot tea. In many patients who ingest large quantities, total elimination may be unrealistic. It is recommended that patients with incontinence and OAB avoid excessive caffeine intake (e.g., no more than 200 mg/d; 2 cups). D.

Bowel Regularity

Chronic constipation and straining during defecation can contribute to LUTS and pelvic organ prolapse. The close proximity of the bladder and urethra to the rectum and their similar nerve innervations make it likely that there are reciprocal effects between them (42). Constipation is defined as having fewer than three stools per week. Usually a patient’s definition of constipation is considerably broader, however, and includes straining during defecation, painful defecation, dry hard stools, small stools, and incomplete or infrequent stool evacuation. Studies of severely constipated women who have strained during defecation over a prolonged period have demonstrated changes in pelvic floor neurological function (43). Lubowski et al. (44) reported that denervation of the external anal sphincter and pelvic floor muscles may occur in association with a history of excessive straining on defecation. Many believe that if these are lifetime habits, they may have a cumulative effect on pelvic floor and bladder function. Spence-Jones et al. (45) found that straining excessively at stool was significantly more common in women with stress UI and in women with prolapse. Moller et al. (46) reported an almost uniform positive association between straining at stool and constipation and LUTS in women (N ¼ 487) 40 years of age. Moller postulated that chronic constipation and repeated straining efforts induced progressive neuropathy in the pelvic floor. Charach et al. (47) examined the effect of alleviating constipation on LUTS in 52 patients aged 65– 89. After constipation treatment with laxatives (e.g., Senokot, lactulose) subjects reported fewer episodes of urgency and frequency. As there are data to suggest that chronic constipation and straining may be risk factors for the development of LUTS, self-care practices that promote bowel regularity should be an integral part of any treatment care plan. Suggestions to reduce constipation include the



addition of fiber to the diet, increased fluid intake, regular exercise, digital stimulation, and establishment of a routine defecation schedule (see Patient Guide #2). Improved bowel function can also be achieved by determining a timetable for bowel evacuation so that the patient can take advantage of the urge to defecate. The schedule should be determined by the patient’s bowel elimination pattern and previous time pattern for defecation. The patient should be taught never to ignore the “call to stool,” the feeling that the bowel needs to be emptied. Combining fluid management, elimination of bladder irritants, and regulation of bowels may be the yield the maximum benefit. Dougherty et al. (48) conducted a randomized, controlled trial in women (N ¼ 218) aged 55 years and older that incorporated reduction of caffeine consumption, adjusting the amount and timing of intake, and making dietary changes to promote bowel regularity, which were termed “self-monitoring activities.” Women in the intervention group also received bladder training and biofeedback-assisted pelvic muscle exercises. Two hundred eighteen women with stress, urge, or mixed UI were randomized, and 178 completed one or more follow-ups. At 2 years the intervention group UI severity decreased by 61%. Selfmonitoring activities and bladder training accounted for most of the improvement.



The Cochrane Collaboration has published systematic reviews for toileting programs which include prompted voiding, habit training, and timed or schedule voiding (49 – 51). Each of these toileting programs are caregiver dependent, which is defined as the need of a professional or family caregiver to assist with toileting. These programs can be utilized to improve continence, and the choice of which program is needed is determined by the cognitive status of the individual, the variability of the voiding pattern, and the need for psychological reinforcement for adherence to the regimen (52). A.

Dependent Scheduled Toileting Programs

A caregiver-dependent program that provides toileting on a scheduled time basis may be the simplest initial approach. If residents in institutions like nursing homes or patients living at home have an available and willing caregiver, a timed toileting program should be established, as at least 60% of care-dependent patients can benefit. The premise of these programs is that if the person is toileted on a preplanned schedule, the bladder will be emptied before incontinence occurs. These patients may have mobility or cognitive impairment and may need assistance (e.g., one-person assist), but may be able to cooperate with toileting. Studies suggest that while fewer than 20% of frail elders become completely dry, 30– 50% of incontinent elders improve with reduction in the number and amount of incontinence episodes. B.

Habit Training

Habit training, first described in England as “bladder drill,” is toileting a person on a rigid, fixed schedule. Toileting takes place whether or not a sensation to void is present but is usually only followed during waking hours. The goal is to keep the person dry, and no effort is made to motivate the person to resist urgency and to delay urination. Prefixed times such as every 2 h have been adopted for toileting programs in institutions such as nursing homes. However, a more realistic schedule may be related to certain daily routines such as upon awakening, mid-morning before or after meals, and at bedtime.

Behavioral Treatments



Prompted Voiding

Prompted voiding (PV) is a type of scheduled toileting program that employs behavior modification to reinforce both appropriate toileting behaviors and the individuals’ desire to stay dry. PV is used for patients who are able to recognize urine leakage and are able to respond (will void) when prompted. PV stresses active communication and interaction between a caregiver and patient allowing the patient to take an active part in their incontinence and toileting behavior. Characteristics of “high responders” (53,54) or those who were more likely to make the greatest improvement in their incontinence include: Has a bladder capacity of at least 200 cc and , 600 cc Maximum voided volume . 150 cc Postvoid residual , 200 cc Has a small number (,4 times/12 h) of incontinent episodes per day Responds to caregivers if prompted (asked and taken to the toilet) to void Ability to ambulate independently or with assistance of one person There are five major steps of a prompted voiding program that includes scheduled checking to allow the patient to request toileting, discussing with the patient the incontinence problem, prompting the patient to void, providing positive reinforcement to the patient for making an effort to use the toilet, and if incontinent, indicate to the patient that the expectation is that they stay dry. Like habit training, this program is for frailer, older patients who require assistance from family members and/or professional caregivers. At least 25 –40% of patients respond well to PV while approximately 38% cannot successfully toilet even when provided assistance by caregivers (53,55). Another caregiver-dependent PV program involves toileting residents and other caredependent patients at times when they are most likely need to void, which are determined by tracking voiding and UI and determining patterns using computerized recordings of wetness (56,57). Despite documented research and positive outcomes, PV interventions have not been adopted by the staff in institutionalized settings such as nursing homes. There is a wide gap between what is known and what is actually used. Research has documented the success of a program called Behavioral Supervision Model, which defines responsibilities of staff members for the prompted voiding intervention, staff feedback regarding performance, and consequences based on staff performance evaluation (58). A novel staffing model that employed a “designated” versus an “integrated” role in nursing homes of the certified nursing assistant (CNA) in the delivery of a restorative care (walking program, exercise therapy) may have application to delivery of continence care (59). D.

Independent Bladder Training

Bladder training is also commonly referred to as bladder retraining, as well as bladder discipline, bladder drill, and bladder reeducation and is an education program that involves learning and independent micturition behavior by the patient. E.

Bladder Training

Bladder training (BT) requires patients to resist the sensation of urgency, to postpone voiding, and to urinate by the clock rather than in response to an urge. Mechanisms of action are not well



understood, but it is felt that bladder retraining improves cortical inhibition over detrusor contractions, facilitates cortical ability over urethral closure during bladder filling, strengthens pelvic striated muscles, and alters behaviors that affect continence (e.g., frequent response to urgency). The goals of a BT program are to: Improve bladder overactivity by controlling urgency and decreasing frequency Increase bladder capacity Reduce urge incontinence episodes Jeffcoate and Francis (60) originally introduced bladder training that was called “bladder drill” by implementing the program in hospitalized patients with bladder dysfunction secondary to psychological disorders. At that time, it was prescribed for functional disorders of the bladder for which surgical intervention was not expected to be successful. The management regimen included education followed by a strict schedule of voluntary voiding with specific instructions to avoid responding prematurely to urinary urgency. This type of bladder training was the basis of a randomized controlled clinical trial of 123 women with detrusor instability, stress, and mixed UI. Results on the group taught BT reduced number of incontinent episodes by 57% and quantity of urine loss was reduced by 54% (61). In addition, BT significantly improved the quality of life, specifically in the ability to carry out activities and relationships, to tolerate and control symptoms and in improved ability to cope (62). In the behavioral intervention research that focuses on persons with urge or mixed incontinence, BT is an integral component. The Cochrane database includes a systematic review of bladder training (63). BT is most appropriate for patients who have: Stress, urge, or mixed incontinence Cognition; are mentally intact Ability to sense the urinary urge sensation Comprehension; can read and follow instructions Motivation; willing to comply with a structured education program Prior to beginning a BT program, the patient should be educated about the lower urinary tract, causes of urinary incontinence, and concepts of bladder urgency using easy-tounderstand visual aids such as “the urinary urge” (see Patient Guide #3). Education should include the fact that “continence” is a learned behavior and the importance of the brain’s control over lower urinary tract function. The clinician initiates the program by assigning a voluntary voiding schedule, which includes voiding every 30 –60 min (64). The voiding intervals are based on the baseline micturition frequency as determined by the bladder diary. The initiation of BT with very short voiding intervals is particularly important for patients who are experiencing urgency, as the shorter intervals will decrease or eliminate these symptoms (61,65). The goal is for the patient to void “before” the urge sensation of bladder fullness. Depending on the patient’s ability to keep the schedule and/or evidence of reduction of incontinence episodes and/or urinary urgency and frequency, the scheduled intervals between voiding is increased by 30 min until the patient can achieve a goal of voiding every 3 – 4 hr. In many cases, patients find this schedule difficult. Therefore the patient should be told to adhere to this schedule at least 75% of the day, and it is not realistic to expect patients to maintain this voiding schedule during the night. The use of reminders such as a kitchen timer or stop watch can be beneficial to helping the patient keep on a schedule (66). Self-monitoring through the use of bladder diaries is used to evaluate adherence and to determine the next weekly voiding interval. Another essential part of BT patient education focuses on the cortical ability to delay voiding and strategies for distraction. Concentration on an attentional task is useful in distracting

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the individual from the sensation of urgency (65). The patient is taught methods to resist or inhibit the urge sensation so that an expanded voiding interval can be adopted. Improving the ability to suppress the urge sensation and eventually diminish urgency will enable the patient to adopt a more normal voiding pattern. There are several bladder control strategies or techniques used to inhibit the urge sensation (67). They include: Slow, deep breathing to consciously relax the bladder to combat a stressful rush to the toilet Performing five or six rapid, deliberate, and intense pelvic muscle contractions, or “quick flicks” which are 2 – 3 sec in duration As with most behavioral interventions, the relationship between the clinician and patient is very important to the success of the retraining. The clinician must monitor the patient’s progress and provide praise and encouragement where appropriate. The use of a signed patient agreement or “contract” with the patient stating personal outcome goals can be helpful in motivating the patient to adhere to the program and outlines expectations. It has been shown that women with incontinence have diverse goals for incontinence treatment, which in some cases may be improvement in urine leakage and not continence (68). It is felt by most experts that combining behavioral interventions with treatments such as drug therapy would increase symptom reduction. Mattiasson et al. (69) reported on a multicenter, single-blind Scandinavian study of 505 subjects, predominantly women (mean age 63) with symptoms of OAB with and without urge incontinence that were either treated with tolterodine 2 mg BID or tolterodine 2 mg BID and bladder retraining (BT). Subjects in the BT group were provided with a written information sheet that outlined the principles of BT and explained simple techniques that could be used to help improve bladder control. Both groups received bladder diaries to track outcomes. Seventy-eight percent of subjects completed 24 weeks of treatment. The median percent reduction of voiding frequency for those receiving drug therapy plus BT was 33% compared with 25% reduction in those subjects on drug therapy alone. There was no significant difference between the groups in relation to reduction in incontinence episodes or urgency. The authors term this approach as a “minimalist” approach, as there was no physician or other professional. They feel this negates the need for an extensive personal interaction between the patient and clinician; however, this is the only study that has shown this technique. Other such programs have not been successful (70).




Pelvic Muscle Exercises

Dr. Arnold Kegel, an obstetrician-gynecologist, introduced pelvic muscle exercises in the late 1940s by implementing a comprehensive program of progressive contractions of the levator ani muscle that incorporated biofeedback technology and was under direct supervision of a trained nurse. Dr. Kegel demonstrated in several clinical trials that practicing these exercises decreased stress urinary incontinence in childbearing women (71,72). These Kegel exercises, or as they have become know as pelvic muscle exercises (PMEs) or pelvic floor muscle training (PFMT), have been shown to decrease LUTS of incontinence, urgency, and frequency (3). The actual effects of PMEs on lower urinary tract function is not completely understood; some studies show a relationship between changes in various measures of pelvic floor strength, such as anal sphincter strength or increased urethral closure pressure and resistance, all of



which will prevent urine leakage (73 –77). The proposed mechanisms of action for PMEs are that: 1. A strong and fast pelvic muscle contraction closes the urethra and increases urethral pressure to prevent leakage during sudden increase in intra-abdominal pressure (e.g., during a cough) (78,79). Urethral compression can be maximized by timing the muscle contraction at the exact moment of intra-abdominal force (called the “knack”) (80 –83). 2. Rising intra-abdominal pressure (e.g., during coughing, laughing, sneezing) exerts a downward (caudal) pressure or force on the bladder and urethra (84). Contraction of the levator ani exerts a counterbalancing upward (cephalic) force by lifting the endopelvic fascia upon which the urethra rests and pressing it upward toward the pubic symphysis, creating a mechanical pressure rise (85,86). 3. Muscle contraction causes a pelvic muscle “reflex” contraction that precedes increased bladder pressure and may inhibit bladder overactivity. The aim is to acquire learned reflex activity. As part of a rehabilitation program, PMEs increases support to the urethral sphincter and detrusor muscle, thus preventing stress, urge, and mixed UI and is most appropriate in patients: Who do not have cognitive impairments Have the motivation to comply with the program Have a pelvic floor that is neurologically intact The goal of PFMT is to isolate the pelvic floor muscle, specifically the levator ani (80,87 – 89). The PFMs are a striated, skeletal muscle group under voluntary control. PMEs consist of repeated, high-intensity pelvic floor muscle contractions of two types of muscle fibers: type I, slow-twitch muscle fibers, and type II, fast-twitch muscle fibers. At least 80% of the levator ani muscle is type 1 muscle fibers. These fibers produce less force on contraction and assist in improving muscle endurance by generating a slower, more sustained, but less intense, contraction. Over time the continuous, though lower-intensity contraction of these muscle fibers maintains a general level of support and urethral closure pressure. Type I muscle fibers are also fatigue resistant. The second group is type II, or fast-twitch, fibers, which aid in strong and forceful contractions. These fibers come into play during sudden increases in intra-abdominal pressure by contributing to urethral closure. By exercising these fibers, pelvic muscle strength will increase. Muscle inactivity, aging, and innervation damage can contribute to a decrease in the proportion of type II fibers. As type II fibers fatigue easily, patients are taught to perform rapid, repeated contractions in exercising them (75,76). The functional demands on the fibers of PFM include sustaining force over time, especially during increases in intra-abdominal pressure, developing force quickly and contracting and relaxing voluntarily (90). During voiding, the person must relax the PFM to open the external urethral sphincter to allow voiding. When these muscles do not function properly, women in particular may develop stress UI, fecal incontinence, and pelvic organ prolapse. Dr. Kegel described four phases in the performance of PMEs (91): 1. Awareness of the function and coordination of the PFM muscle. For older adults and persons whose pelvic muscle is severely relaxed, this may take several weeks. 2. Gains over muscle identification, control, and strength. Muscle strength is the maximal force that can be generated by the PFM. Although the PFM is not flexible, the muscle must adapt to different or changing requirements so the PFM must have contractibility and build force quickly when contracting. 3. Firmness, thickening, broadening, and bulking of the muscles to increase muscle endurance. Muscle endurance is a performance characteristic of the ability of the PFM to

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execute repeated contractions to and initial level of strength often called a “submaximum” contraction. 4. Improvements of the symptoms indicate that the muscles are strengthening. At this point some patients feel that their LUTS are so improved that regular exercising is no longer needed. For muscle contractility to improve, the initial muscle strength, power, endurance, repetitions, and fatigue must be considered together with the principles of muscle training (92). The following are the definitions for determining pelvic muscle contractility: Strength—the maximum force or contraction that a muscle can generate. Power—the ability for the muscle to “contract-relax” as quickly and strongly as possible, until the muscle fatigues. These are often called “quick flicks.” Endurance—this is the time, up to 10 sec, that the maximum muscle contraction can be maintained or repeated, before a reduction in power of 50% or more is detected. In other words, the muscle contraction is timed until the muscle fatigues. Repetitions—the number of repetitions (up to 10) of the muscle contraction of equal force that can be repeated. Use at least a 5-sec muscle relaxation between each two contraction; easily fatigable muscles need a chance to recover, without permitting excessive rest periods for strong muscles. Fatigue—failure to maintain the required or expected force of the pelvic muscle contraction for more than one or two times in succession. The following definitions can be applied to pelvic floor muscle dysfunction: 1. Low-tone is the clinical finding of an impaired ability to isolate and contract the pelvic floor muscles in the presence of a weak and atrophic PFM. Ideally, the patient will gain the ability to recognize the difference between relaxation and contraction. 2. High-tone refers to the clinical condition of hypertonic, spastic PFM with resultant impairment of muscle isolation, contraction and relaxation. A high resting baseline with high variability and occasional spasms may be seen in patients with chronic pelvic pain syndromes. In some cases, this excessive, elevated resting tone may be created unconsciously. Therapeutic exercise is important in the management of pelvic pain as the patient often has a reduced level of activity related to the prolonged nature of their pain. Rehabilitating the pelvic muscle can be central in resolving pain when muscle spasm is present. Using PMEs on patients with high-tone to enhance muscle relaxation is referred to as “downtraining.” Teaching a muscle to relax is often more difficult than teaching it how to contract (uptraining), as the feeling of relaxation is small. The patient should be cautioned not to: 1. Perform these exercises during voiding and not to stop and start urine flow as a form of exercising. This exercise has good face validity for effectiveness because many patients initially report an inability to stop the urine flow when it begins. However, there is some controversy over this practice because it is nonphysiological and can be harmful (93). 2. Over-exercise the pelvic muscle. Women can develop levator ani myalgia by performing excessive PFM exercises to reduce incontinence (94). Start slowly, building gradually. Patients should be instructed on the correct technique of pelvic muscle exercises. Patients have a difficult time identifying and isolating this muscle. Without sufficient information, women may mistakenly bear down or exercise ineffectively. Specifically, women are told to “draw in” and “lift up” of the perivagin*l and anal sphincter muscles. Once patients are able to identify the muscle, they are instructed to perform a series of “quick flicks,” or 2-sec contractions, followed by sustained (endurance contractions) contractions of 5 sec and longer as part of a daily exercise regimen (see Patient Guide #4). At least 10 sec of relaxation is



recommended between contractions. Encourage the patient to aim for a high level of concentrated effort with each pelvic muscle contraction, as greater contraction intensity is associated with improvement in pelvic muscle strength (74,76). Patients are given verbal and written instructions for a daily exercise program based on the baseline assessment of the patient’s PFMs strength, contraction, and endurance during the initial assessment session. Visual aids are helpful (see Figs. 1, 2). Patients should be encouraged to aim for a high level of concentrated effort with each pelvic muscle contraction, as greater contraction intensity is associated with improvement in pelvic muscle strength (74,76). Patients are instructed to exercise at least twice daily and to perform the exercises in three positions—lying, sitting, and standing. A minimum of 30 – 45 PMEs per day is recommended (95). A gradual increase in number of contractions over a period of PME practice has been shown to increase muscle strength significantly and decrease urine loss. The patient should be instructed to contract the muscle at the time of the UI episode (81,95). Contracting it before sneezing, coughing, lifting, standing or swinging a golf club can prevent stress UI from occurring (see Patient Guide #4). The muscle also can be contracted when a strong urge to void occurs. Results may not occur until after 6 –8 weeks of exercise, and optimal results usually take longer. Self-monitoring practice through the use of a calendar record, audio, and video taped material that review the exercises can improve protocol compliance (37,96). Most clinicians in this field have relied on the use of verbal and written instructions for patients to use for home practice of PMEs, not the use of a home biofeedback device. There is a paucity of research on the use of a home biofeedback device to aid in performing these exercises at home while providing information to the clinician and patient about the success of the muscle contraction (97,98). Teaching women to strengthen the pelvic floor muscle as part of a comprehensive behavioral program has been demonstrated to be effective in 50– 60% of women with SUI. However, even after they have learned to do that, there is the additional problem that many find too burdensome—the daily exercises necessary to increase muscle strength and control. As a result, the noncompliance rate for this therapy can be high, varying from 10% to 40%. This can

Figure 1 Pelvic floor muscle in men. # 1995 Diane K Newman

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Figure 2 Pelvic floor muscle in women. # 1995 Diane K Newman

be frustrating to clinicians who provide these treatments, as poor outcome may be secondary to noncompliance and out of their control. Research in the area of PMEs is extensive but long-term results have been reported only rarely (99). Cammu et al. (100) found that in women who had been successful with PMEs initially, two-thirds maintained their success 10 years later. Practice of PMEs in primiparas results in fewer UI symptoms during late pregnancy and postpartum (101). Subak and colleagues (22,23) conducted a randomized trial for community dwelling women who at least reported one UI episode per week. Women were randomly assigned to the behavioral therapy (n ¼ 77) and control (n ¼ 75) group. Women in the behavioral therapy were asked to keep urinary diaries and attend six weekly 20-min group instructional sessions with three to five participants on bladder retraining and written and verbal instructions on PMEs, which was termed a “low-intensity” behavioral therapy. Women in the control group did not receive any instructions but were asked to keep urinary diaries for 6 weeks. At 6 weeks, the treatment group had a 50% reduction in mean number of incontinence episodes compared with a 15% reduction or the control group. They also experienced improved diurnal and total incontinence frequencies. The Association of Women’s Health Obstetric and Neonatal Nurses (AWHONN) tested the efficacy of a bladder and pelvic floor muscle training program in real-world ambulatory care settings (88,102,103). Twenty-one clinical sites participated yielding a sample of 132 women with a mean age of 51 years that originally screened positive for incontinence, received instruction in bladder and pelvic floor muscle training, and persisted to a point of follow-up 4 months posttreatment. Significant reductions were noted between pre- and posttreatment in the frequency of incontinent episodes, the volume of leakage per episode, the cost of selfmanagement, and the frequency of nocturia. Simultaneously, significant improvements were reported in indices reflecting quality of life. Specifically, women indicated that the incontinence was less bothersome and that they were avoiding fewer activities because of their incontinence. These results demonstrate the effectiveness of an evidence-based protocol in actual clinical settings and warrant the implementation of the protocol by nurses in general ambulatory women’s health care settings across the United States (104).




Use of EMG or Manometric Measurement

Pelvic floor muscle strength is either measured by electromyography (EMG) or manometric pressure. Most clinicians who specialize in this field prefer EMG measurements. EMG is the graph of the electrical activity of a muscle and as a practical indicator of muscle activity has been defined as: The study of electrical potentials generated by the depolarization of muscle A monitor of bioelectrical activity correlating to motor unit activity; it does not measure the muscle contractility itself but the electrical correlate of the muscle contraction An indicator of the physiological activity The advantage of EMG over manometric pressure is that, provided the machinery is of sufficient sophistication with adequate filtering, EMG apparatus can engage the use of the newer types of electrodes that are lightweight and designed to stay in place, hence allowing more functional positions during assessment and treatment (92). An added benefit is that EMG can be multichannel, which allows the simultaneous reinforcement of contractions of the pelvic floor muscles and inhibition of accessory muscles (e.g., abdominal muscle contractions). A common error in contracting the PFM is to simultaneously contract the abdominal, gluteal, or adductor muscles. This may mask the strength of the PFM contraction. Abdominal contraction increases intra-abdominal pressure, which mechanically elevates bladder pressure, so it is important to measure concurrent use of abdominal contraction (105). For the PMR treatment to be successful, it is essential that the patient be able to isolate the pelvic floor muscles. When an additional muscle group is contracting at the same time of the pelvic floor, it is called “recruitment.” Monitoring for accessory muscle recruitment during initial EMG and subsequent visits are necessary until recruitment stops and should be considered on all patients. The use of multichannel EMG can be especially helpful in patients who are having difficulty identifying and isolating the correct muscle. Four methods of EMG measurements have been used in the investigation of lower urinary tract dysfunction (106): vagin*l sensor Anal sensor or plug electrode (anorectal) Surface skin electrodes Needle electrodes vagin*l and anal sensors are designed to provide accurate detection of EMG muscle activity. The accuracy of longitudinal sensing electrodes has been shown to be virtually identical to the gold standard, inserted needle electrodes. The use of vagin*l or rectal sensors is contraindicated in the following: Active vagin*l infection or genital disease Severe pelvic pain where insertion of the sensor causes vagin*l or rectal discomfort Pregnancy Recent (within last 6 months) pelvic or rectal surgery Untreated atrophic vaginitis Dyspareunia Menstrual period In these cases consider the use of skin surface electrodes. Surface skin electrodes are relatively non-invasive and well tolerated. They give quantitative information about muscle activity rather than data for qualitative analysis. The first choice of electrode placement is at the 10 and 4 o’clock or 9 and 3 o’clock position on either side of the anus (see Fig. 3). Electrodes should be

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Figure 3 Surface skin electrode placement

placed close to the anus without touching the other sensor or without sensors overlapping. Needle electrodes are primarily used during urodynamic testing. The EMG data are measured in microvolts. The actual threshold of pelvic muscle strength required for maintaining continence is unknown at this time as is unknown the normal values for pelvic muscle strength. The baseline and all follow-up EMG recordings should include two set of measurements of: First Set: Maximum or “short/quick” muscle contractions of 2-sec duration Resting muscle activity of 2-sec duration Second set: Sustained or “long” muscle contractions (5, 10, or 30 sec); the clinician should not go directly from 3- to 10-sec muscle contractions but increase in increments of 5 sec as patient’s ability warrants Resting muscle activity of 5-sec duration or for the same length of time as muscle contraction

The ability to relax one’s pelvic muscle following a contraction is of most importance if one is to gain control and coordination of these muscles. Manometry is the use of an instrument to detect, assess, and record pressure. A pressure perineometer consists of a vagin*l or rectal probe with a connector tube to a manometer. Dr. Arnold Kegel first used the term “perineometer” for a vagin*l pressure gauge specific to the PFM. He developed this instrument for both diagnosis and nonsurgical treatment for women with stress UI and pelvic muscle relaxation. Perineometers aim to show changes in pressure caused by the contraction of the perivagin*l musculature, to be observed on a manometer gauge. The pressure changes can be measured in centimeters of water (cmH2O) or millimeters of mercury (mm Hg). Depending on the sophistication of the equipment, the pressure changes may be shown on a dial, a digital readout, a bar chart, or a graphical representation. Different types of probes—air-filled, water-filled, individually made, and mass produced—have been reported and can be performed by inserting sensors into the vagin* or rectum. Although manometry and pressure sensors are available with certain clinical systems and have been used in several clinical trials, they are primarily used for treatment of rectal dysfunction (e.g. constipation, fecal incontinence), not for treatment with LUTS. Theofrastous, Wyman et al. (107) used two waterfilled balloon manometric devices to measure vagin*l and abdominal pressures. The group who



received a pelvic floor muscle training regimen demonstrated a 15– 23% improvement in pelvic muscle strength. C.

Application of Biofeedback Therapy

The use of biofeedback therapy is a method of assessment and treatment of pelvic floor dysfunction. Biofeedback relayed using EMG, when used as part of a pelvic muscle rehabilitation program, is a method by which the patient is immediately made aware of the physiologic state of the PFM. Feedback to the patient is in the form of tactile, verbal, visual, or auditory methods. Biofeedback treatment may assist muscles that have increased tension even when the patient or clinician cannot detect it. This is particularly true of the pelvic floor muscles, as denervation damage may lead to impaired sensation. High levels of resting activity and fleeting muscle spasms may be only visualized using EMG biofeedback instruments. Muscle training that utilizes EMG biofeedback may improve the effectiveness of the muscle relaxation efforts while strengthening weak pelvic muscles. A biofeedback-assisted exercise program that stabilizes the pelvic floor muscles can reduce and eliminate symptoms of pelvic floor dysfunction as seen in chronic pelvic pain syndromes. Generally, visual, auditory, or verbal feedback techniques are used for neuromuscular conditioning. These methods help to reinforce a particular task being performed. For example, the display on a monitor screen of the pressure, or the EMG changes of the anal sphincter, provide instant visual feedback to the patient regarding their performance. Similarly, during muscle contraction the intensity (pitch of the electrical activity) of the sphincter muscle provides corresponding auditory feedback to the patient regarding their performance. To determine PFM strength, two indices recommended as outcome of muscle strength tests that can be recorded on the EMG are the peak muscle contraction value and the average score. EMG or manometry can record the following variables of the PFM: Strength—recorded as the peak or maximum contraction that has the highest waveforms indicating ability to sustain the muscle contraction Endurance—average muscle contraction measured across the waveform Contractibility—the rate of the original rise of the muscle contraction Throughout the treatment session, the clinician reinforces the patient’s behavior and provides compliments and other appropriate advice. This constitutes verbal feedback to the patient and is an essential part of a behavioral treatment program. All three maneuvers are complimentary. Motivation and active participation play a big part in the success of biofeedback therapy. For incontinence and other LUTS, biofeedback therapy uses computer graphs or lights as a teaching tool to help the patient identify and learn to control the correct muscles. Biofeedback helps the patient locate the pelvic muscles by changing the graph or light when the patient contracts or tightens the correct muscle. Different biofeedback methods can be used in pelvic floor muscle (PFM) reeducation, including proprioception and verbal encouragement during: 1. Digital (e.g., vagin*l or rectal) PFM assessment of the levator ani muscle is a form of biofeedback and is an important component of teaching correct pelvic muscle contraction and muscle awareness (108). Verbal feedback of a voluntary contraction can also encourage and assist in enhancing patient effort. A digital measure of pelvic muscle strength can be performed based on pressure, duration of contraction, and displacement of the examiner’s finger. Palpation of muscular attachments along the pubic arch and the insertion of the levator ani and coccygeus muscles are part of the assessment. The levator ani can be palpated just superior to the hymeneal ring. Palpate the levators at the 4 and 8 o’clock positions to determine if that reproduces any discomfort or

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tenderness. There are several different grading systems (examples are found in Tables 1 and 2) that can be used to assess and document pelvic muscle strength in women. Using the scale described in Table 1, a scale, assess pressure, which is defined as the strength of contraction on the finger. Scores range from 0 for no pressure felt to 5 for strong compression, where the examiner’s finger(s) are gripped. Ask the patient to squeeze hard and count in seconds to determine the duration of the contraction, which is recorded in seconds. Note the displacement in plane by the amount of movement of your finger(s) when the patient contracts her muscle. The rating scale starts with 1, which is no displacement, to 5 when the examiners finger are moved upward and drawn in by the contraction of the pelvic muscle. It may be helpful to perform a digital PMA pre- and posttreatment to determine the increase in muscle strength, strength, and ability to isolate the levators. 2. Manometric and EMG biofeedback helps in PFM awareness, but also provides interest, challenge, and reward for effort, a greater feeling of control, and progress in monitoring (109). Research is extensive detailing the efficacy of the use of biofeedback-assisted behavioral therapy for PFMT (110 –116). The 1996 guideline on Urinary Incontinence in Adults (3) outlined the research that demonstrated that PMEs are indicated for patients with stress incontinence and can reduce urgency and prevent urge UI. Pelvic floor reeducation has proven to be effective in women with sphincter deficiency and detrusor instability. More recent research has supported this claim (101,117,118). Behavioral modifications, pelvic muscle rehabilitation, and bladder retraining programs have successfully decreased UI in homebound elders (119,120). A study of men with urinary incontinence following radical prostate surgery showed that 88% of the treatment group achieved continence in 3 months compared to 56% of the control group (121). Wyman and colleagues (122) randomized 204 women into three groups. Group 1 was encouraged to use bladder training with the voiding interval set at 30 or 60 min and increased by 30 min each week. Group 2 received pelvic muscle instruction that included four office biofeedback sessions; women were instructed to perform five fast and 10 sustained contractions twice a day and work up to a total of 50 contractions by the third week. Participants were also instructed to use pelvic muscle contractions for urge inhibition and preventive contractions with exertional events. Group 3 received a combination of the two therapies. There were no significant differences found pretreatment in any of the outcome variables. At the short-term follow-up 2 weeks after treatment, the combination therapy group had significantly fewer incontinent episodes, better quality of life, and greater satisfaction with treatment. However, by 3 months posttreatment, all three treatment groups had improved relative to baseline status. The absence of differences among the three groups led the investigators to conclude that the type of therapy (bladder or pelvic floor muscle training) may be less important than participation in a structured intervention program. Dougherty and colleagues (48) randomized 218 women, aged 55 and older who were provided treatment in their home by a trained nurse practitioner. Group 1 was a control group. Group 2 received a behavioral management for continence (BMC) program that consisted of sequenced phases: (a) self-monitoring, (b) bladder training, and (c) biofeedback-assisted pelvic muscle exercises. The BMC treatment was not found to have a significant impact on either urinary frequency or voiding intervals. Amount of urine loss decreased in 61% of the BMC over the 2 years of follow-up, whereas the control group’s urine loss worsened by 184%. However, both the BMC and control groups’ episodes of urine loss decreased (70% and 16%, respectively). Burgio and associates (123) compared the effectiveness of anorectal biofeedback-assisted behavioral therapy for PFMT with drug therapy and placebo control and showed that the behavioral intervention was more effective with 80% of those receiving behavioral experienced a reduction in incontinence episodes compares with 68.5% if those receiving drug therapy and only 39.4% of those receiving placebo.

Seconds maintained


Source: Brink et al. (124).



Flick, more than one point, but not a full circumference (instant, mild pressure) Base lifting




Table 1 Pelvic Muscle Rating Scale

Base to midfinger

Felt at more than one point but not a full circumference (instant, mild pressure)


Base to fingertip; lifting, gentle lift at tip

Loose hold (full circumference)



Base to fingertip; lifting, strong lift at tip

Snug (full circumference)


Vigorous drawing up and in

Strong compression of fingers


250 Newman

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Table 2 Modified Oxford Scale for Pelvic Muscle Assessment Grade


Nil Flicker

0 1









No discernible PFM contraction Feels like a flicker or a pulsation and represents a very weak contraction Weak contraction, is detected as an increase in muscle tension, without any discernible lift or tightening A moderate contraction characterized by a degree of lifting of the posterior vagin*l wall, tightening of the examiner’s finger (pubovisceralis) and drawing in of the perineum. A grade 3 as well as a grade 4 and 5 contraction is generally discernible on visual perineal inspection. Produces elevation of the posterior vagin*l wall against resistance (applied as pressure to the posterior vagin*l wall) and drawing in of the perineum. If two fingers (index and middle) are placed laterally in the vagin* and separated, a grade 4 contraction can squeeze them together against resistance. Strong resistance can be given against elevation of the posterior vagin*l wall and approximation of the index and middle fingers.

Clinician-supervised PME with biofeedback is felt to provide the most favorable longterm results and many multidisciplinary pelvic floor dysfunction or “continence” centers provide these services (37). Berghmans et al. (125,126) reviewed the literature regarding biofeedbackassisted PMEs in women with stress and urge UI and felt there was a need for more research to support these more intensive therapy regimens. The most recent study was conducted by Burgio and colleagues (127) in women (n ¼ 222) who had urge UI. Women were randomized to three treatment groups: Group 1 received behavioral training that consisted of bladder retraining and PMEs with anorectal biofeedback. They had four clinic visits with nurse practitioners at 2-week intervals with a home program of PMEs. Group 2 received behavioral training without biofeedback but digital pelvic muscle assessment with information on muscle isolation and correct identification and was given a home program of PMEs. Group 3 were given a 20-page self-administered booklet that included an 8-week step-bystep, self-help instructions on bladder retraining, and PMEs. Results indicated that the outcomes of the three groups were not significantly different. Group 1 had 63.1% reduction in frequency of UI episodes, group 2 had 69.4% reduction in frequency of



UI episodes, and group 3 58.6% reduction in frequency of UI episodes. However, patients’ perceptions of treatment were significantly better for groups 1 and 2.


Combining Behavioral Treatments with Drug Therapy

In addition, a more recent study (128) examined the effects of combining behavioral treatment and drug treatment for urge UI in ambulatory women. Subject’s reduction of incontinence went from a mean 57.5% with behavioral therapy to a mean 88.5% overall reduction with combined behavioral and drug (anticholinergic) treatment. The majority of the PME research used biofeedback therapy to teach and train the PFM.


Use of vagin*l Weights

vagin*l weights are another example of a biofeedback technique, which educates women on contraction of the PFMs. They have been most successful in woman with stress incontinence, and can be used by the patient as part of a structured resistive pelvic muscle exercise program. The weights are made of plastic and shaped like cones and are of increasing weights. The user is instructed to insert the lightest weight into the vagin*, in the position of a tampon. It should be inserted so that it cannot be felt protruding from the opening of the vagin*. The user then walks around for up to 15 min. If the weight is retained during this time, the next-heaviest weight is introduced and the procedure is repeated until a weight of a certain weight slips out. The woman uses that weight to practice holding it in, by contracting the pelvic muscles, for up to 15 min BID. When the woman can successfully hold one weight, she is told to switch to a heavier one. To increase the exercise value of these weights, the woman is instructed to practice retaining the weight during coughing, jumping, or any stress-provoking act that causes incontinence. Theoretically, when the weight is placed in the vagin*, it provides sensory feedback and prompts a pelvic floor muscle contraction to keep it from slipping out. The perceived advantages of vagin*l weight training are that it involves less teaching time, can be self-taught, may be motivational, and can be used with minimal supervision. There is strong evidence that indicates it is an effective treatment for stress UI in pre- and postmenopausal women (12), However, the evidence is inconclusive regarding the superiority of vagin*l weight training over PMEs alone or electrical stimulation; further there appears to be no added benefit to use of vagin*l weight training with PMEs (129,130). Although vagin*l weight training may take less instructional time in terms of office practice, it may be less acceptable to some women than PFME alone as noted by higher attrition rates in some clinical trials (131). Reasons given for their nonuse were aesthetic dislike, unpleasantness, discomfort, difficulty of insertion, or bleeding (132).


Pelvic Floor Electrical Stimulation

Pelvic floor electrical stimulation (PFES) is the application of a low grade of electrical stimulation to the pelvic floor muscles (PFMs) to stimulate the muscle to contract. PFES has a twofold action: contraction of pelvic floor muscles, and inhibition of unwanted detrusor contractions. PFES for stress UI is the result of stimulation of afferent fibers of the pudendal nerve activating both the pelvic floor and periurethral muscles. For urge UI bladder inhibition occurs through pudendal (afferent) to pelvic (efferent) nerve reflex and a pudendal to hypogastric

Behavioral Treatments


reflex. The application of electric current to the pelvic floor muscles produces a reflex muscle contraction without any effort on the part of the patient. Pelvic muscle electrical stimulation combined with biofeedback may prove useful in that the electrical stimulation provides a passive contraction with increased awareness of pelvic muscle contractions. The parameters of most stimulation units include the waveform, the current intensity, the pulse frequency, the ramping of impulses, and the on/off timing. The muscle contraction, called neuromuscular stimulation, is a useful addition to pelvic floor exercises in the rehabilitation of weakened pelvic muscles and is very beneficial for both men and women who are unable to contract these muscles on command, as it leads to an improved comprehension of the activity of the muscles and subsequently better active contraction. Also, PFES is used with patients as an adjunct treatment to: Assist with identification and isolation of pelvic muscle Increase pelvic muscle strength Decrease unwanted or uninhibited detrusor (bladder) muscle contraction Assist with normalizing pelvic muscle relaxation There are no documented side effects to electrical stimulation of the pelvic floor, but PFES is contraindicated in the following: Complete denervation of the pelvic floor (will not respond) Dementia Demand cardiac pacemaker Unstable or serious cardiac arrhythmia Pregnancy or planning/attempting pregnancy Rectal bleeding Active infection (UTI/vagin*l) Unstable seizure disorder Swollen, painful hemorrhoids Presence of vagin*l vault prolapse Pelvic surgery in past 6 months Electrical stimulation is usually performed initially in the clinician’s office than prescribed as a home program using a battery-operated home unit. The delivery of the electrical current to the tissues is via a sensor, which may be on the surface of the skin (skin electrodes around the anus) or by vagin*l or rectal sensors and is used in conjunction with biofeedback. The home program consists of using the stimulator for 15 min BID for several weeks to months, although the length of time and number of treatments is highly variable. However, with the wide variations in stimulation parameters including time, intensity, and frequency of sessions, it is difficult to make comparisons across studies. Given the equivocal results, the benefit of electrical stimulation in stress, urge, and mixed UI in women remains controversial (12). There does not appear to be any consistency to PFES protocols used in clinical practice to treat patients with stress, urge and mixed incontinence. The research in this area is confusing because information is lacking on detail of stimulation parameters (intensity, pulse duration), time PFES is used by the patient, devices used and methods of delivery (133 –138). The Cochrane Database did not find any significant differences between the addition of PFES to a PME program for self-reported cure (139). Goode et al. (140) conducted a RCT of the effect of PFES to a behavioral intervention program in women with stress only or mixed UI. This study was similar to their previous research (127) except that PFES was added. Women (N ¼ 200) underwent an 8-week treatment



program and were asked to complete a daily bladder diary. Women were randomized to three groups: . Group 1 received behavioral training that consisted of anorectal biofeedback-assisted PMEs, home exercises, and bladder control strategies. . Group 2 received same program as Group 1 with PFES (performing both office and home stimulation) using a vagin*l sensor. . Group 3 or control condition consisting of a self-administered self-help book on behavioral treatments. Results indicated that the addition of PFES did not seem to enhance the results of behavioral training alone however, behavioral training with or without PFES were significantly more effective than the self-help book. Actual results showed that behavioral training resulted in a mean 68.6% reduction in frequency of UI episodes, behavioral training with PFES resulted in a 71.9% mean reduction and treatment with the self-help book a 52.5% reduction. The authors felt that the two treatments of PMEs and PFES may overlap. This reinforces other research noted in this chapter on behavioral interventions that suggest that this treatment is optimally implemented in a clinical practice setting with trained professionals (doctors, nurse practitioners or nurses) to ensure that patients are exercising the correct muscle. Also, a stepped approach in which biofeedback and PFES are added to a less invasive program such as PMEs and lifestyle changes is the preferred clinical approach and is supported by current reimbursem*nt (141).


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Newman Bent AF, Sand PK, Ostergard DR, Brubaker L. Transvagin*l electrical stimulation in the treatment of genuine stress incontinence and detrusor instability. Int Urogynecol J 1993; 14:9– 13. Brubaker L, Benson JT, Bent A, et al. Transvagin*l electrical stimulation for female urinary incontinence. Am J Obstet Gynecol 1997; 177:536 – 540. Luber KM, Wolde-Tsadik G. Efficacy of functional electrical stimulation in treating genuine stress incontinence: a randomized clinical trial. Neurourol Urodyn 1997; 16:543 – 551. Richardson DA, Miller KL, Siegel SW, Karram MM, Blackwood NB, Staskin DR. Pelvic floor electrical stimulation: a comparison of daily and every-other-day therapy for genuine stress incontinence. Urology 1996; 48:110– 118. Sand PK, Richardson DA, Staskin DK, Swift SE, et al. Pelvic floor electrical stimulation in the treatment of genuine stress incontinence: a multicenter, placebo-controlled trial. Am J Obstet Gynecol 1995; 173:72 – 79. Yamanishi T, Yasuda K, Sakakibara R, Hattori T, Suda S. Randomized, double-blind study of electrical stimulation for urinary incontinence due to detrusor overactivity. Urology 2000; 55:353–357. Hay-Smith EJC, Bo K, Berghmans LCM, Hendriks HJM, de Bie RA, van Wallwijk, van Doorne ESC. Pelvic floor muscle training for urinary incontinence in women (Cochrane Review). In: The Cochrane Library, 2002, Issue 2. Oxford: Update Software Ltd. Goode PS, Burgio KL, Locher JL, Roth DL, Umlauf MG, Richter HE, Varner RE, Lloyd LK. Effect of behavioral training with or without pelvic floor electrical stimulation on stress incontinence in women: a randomized controlled trial. JAMA 16 Jul 2003; 290(3):395– 397. Medicare Coverage Issues Manual. Rockville, MD: Center for Medicare and Medicaid Services, Dept of Health and Human Services; 2000. Agency for Health Care Policy & Research, Public Health Service. Urinary Incontinence in Adults: Clinical Practice Guideline (AHCPR Pub. No. 92-0038). Rockville, MD: U.S. Dept of Health and Human Services, 1992. Brubaker L, Benson JT, Bent A, Clark A, Shott S. Transvagin*l electrical stimulation for female urinary incontinence. Am J Obstet Gynecol 1997; 177(3):536– 540. Burgio K, Engel T. Biofeedback-assisted behavioral training for elderly men and women. J Am Geriatr Soc 1990; 38:338– 340. Burns P, Pranikoss K, Nochajski T, Desotelle P, Harwood M. Treatment of stress incontinence with pelvic floor exercises and biofeedback. J Am Geriatr Soc 1990; 38:341– 344. Cammu H, Van Nylen M, Derde M-P, DeBruyne R, Amy JJ. Pelvic physiotherapy in genuine stress incontinence. Urology 1991; 38(4):332– 337. Dietz H, Wilson P, Clarke B. The use of perineal ultrasound to quantify levator activity and teach pelvic floor muscle exercises. Int Urogynecol J 2001; 12:166– 169. Engberg SJ, McDowell BJ, Weber E, Brodak I, Donovan N, Engberg R. Assessment and management of urinary incontinence among homebound older adults: a clinical trial protocol. Adv Prac Nurs Q 1997; 3(2):48 – 56. Ferrie BG, Smith JS, Logan D, Lyle R, Paterson PJ. Experience with bladder training in 65 patients. Br J Urol 1984; 56:482 – 484. Fischer W, Linde A. Pelvic floor findings in urinary incontinence—results of conditioning using vagin*l cones. Acta Obstet Gynaecol Scand 1997; 76: 455– 460. Layco*ck J, Brown J, Cusack C, Green S, Jerwood D, Mann K, McLachlan Z, Schofield A. Pelvic floor reeducation for stress incontinence: comparing three methods. Br J Community Nurs 2001; 6(5):230 – 237. Lekan-Rutledge D, McConnell ES, Anderson RA, Corazzini-Gomez K. Evidence-based practice in long term care: promoting sustainability of prompted voiding. Unpublished manuscript, 2002. Luber KM, Wolde-Tsadik G. Efficacy of functional electrical stimulation in treating genuine stress incontinence: a multicenter, clinical trial. Physiotherapy 1997; 79:553 – 540. Nygaard I, Kreder K, Lepic M, Fountain K, Rhomberg A. Efficacy of pelvic floor muscle exercises in women with stress, urge, and mixed urinary incontinence. Am J Obstet Gynecol 1995; 174(1): 120– 125.

Behavioral Treatments 155. 156.


Palmer MH, Fitzgerald S, Berry SJ, Hart K. Urinary incontinence in working women: an exploratory study. Women Health. 1999; 29(3):67 – 80. Theofrastous JP, Wyman JF, Bump RC, et al. Effects of pelvic floor muscle training on strength and predictors of response in the treatment of urinary incontinence in women. Neurourol Urodyn 2002; 21:486– 490.

Patient Guide #1: Caffeine Chart Source of caffeine Coffee:

Tea (black or green)

Instant tea Iced tea Hot chocolate Soft drinks

Chocolate desserts

Chocolate candy


Cold/allergy Stimulants # 1997 Diane K. Newman

Brewed, drip Brewed, percolated Instant Decaffeinated 1-min brew 3-min brew 5-min brew

Jolt Cola Mountain Dew Coca-Cola Diet co*ke Tab Pepsi-Cola Diet Pepsi Dr. Pepper Red Bull Brownie (with nut) Cake Ice cream Pudding Milk chocolate Sweet, dark chocolate Baking chocolate Anacin Excedrin Vanquish Midol Darvon compound Fiorinal Norgesic Dristan Sinarest No-Doz Vivarin

Serving Size

Caffeine (mg)

8 oz. 8 oz. 8 oz. 5 oz. 5 oz. 5 oz. 5 oz. 5 oz 12 oz. 5 oz. 12 oz. 12 oz. 12 oz. 12 oz. 12 oz. 12 oz. 12 oz. 12 oz. 12 oz. 1.25 oz. 1/16 of 900 2/3 cup 2 cup 1 oz. 1 oz. 1 oz. 2 tablets 2 tablets 2 tablets 2 tablets 2 tablets 2 tablets 2 tablets 2 tablets 1 tablet 2 tablets 1 tablet

100– 164 80– 135 50– 75 2– 4 20– 34 35– 46 39– 50 30 67– 76 2– 15 71 54 60 46 49 43 36 60 106 8 14 5 6 1– 15 20 25– 35 64 130 66 64 65 80 30 32 30 200 200



Patient Guide #2: Maintaining Bowel Regularity Sometimes urinary incontinence, urgency, and frequency may be aggravated by increased pressure on the bladder from the pressure related to constipation or stool (hard) impaction. Eating foods that have a lot of fiber helps overcome this problem. Fiber-rich foods include whole-grain breads, brown or wild rice, cereals, nuts, and raw fruits and vegetables. Apricot juice has more fiber content than prune juice. Another way to increase your fiber is by using a special bran recipe. How to make “Special Bran Recipe” Mix together: 1 cup applesauce 1 cup coarse unprocessed wheat bran 3 4 cup prune juice

You can buy unprocessed wheat bran in the grocery or health food stores. This type of bran is different from bran cereal.

Refrigerate mixture and take 2 tablespoons of the mixture every day. Take the mixture in the evening for a morning bowel movement. Increase the bran mixture by one tablespoon until your bowel movements become regular. If the amount exceeds 4 tablespoons, take the mixture in divided doses in the morning and evening. Always drink one large glass of water with the mixture. What if I don’t like the “Special Bran Recipe”? Add unprocessed wheat bran to your diet. Start by using 1– 2 tablespoons every day. If necessary for regulation, increase bran slowly over several weeks to approximately 6 tablespoons every day. Mix bran in foods like applesauce, cereals, or sauces, or use it as a spice in gravies or puddings. Sprinkle bran on ice cream, vegetable and fruit salads, or cottage cheese. Add to muffins, breads, and cookies when baking. When will I notice a change? You may notice effects on bowel function 3– 5 days after starting bran or other natural remedies. You should continue to use these remedies. Will bran and other natural remedies harm me? No! The normal reaction to bran is stomach bloating and increased gas. These symptoms usually last for only the 1st week. If symptoms last longer, contact your nurse or doctor. # 2001 Diane K. Newman

Patient Guide #3: Bladder Retraining—Controlling Urgency and Frequency Frequency is voiding often, usually eight times or more in a 24-h period. Frequency can worsen if you get into the habit of voiding “just in case,” which means that the bladder never fills completely and holds only a small amount of urine. It is better to wait until the bladder is full. Urgency is a sudden need to void immediately that can cause urine leakage on the way to the bathroom. Urgency follows a wave pattern; it starts, grows, peaks and then subsides until it stops.

Behavioral Treatments


The key to controlling the urinary urge is not to respond by rushing to the bathroom. Rushing causes movement, which jiggles your bladder, which in turn increases the feeling of urge. Controlling the urge The goal is for you to be voiding no more than every ___ hours. If you get the urge to void and it is not yet your scheduled voiding time, stop all activity and sit down if possible. Then try one or more of the following techniques that may help the urge to subside allowing the bladder to relax and give you more time to get to the bathroom: Take some slow, deep breaths through your mouth, concentrating on your breathing, or Tighten your pelvic muscle quickly and hard several times in a row. Use mental distraction strategies such as concentrating on an activity, such as counting backward from 100 by sevens, or reciting the words of a favorite song or nursery rhyme. # 2001 Diane K. Newman

Patient Guide #4: Pelvic Muscle Exercises & the “KNACK” WHAT IS THE PELVIC MUSCLE ? – Your pelvic muscle provides support to your bladder, and rectum and, in women, the vagin* and the uterus. If it weakens or is damaged, it cannot support these organs and their position can change. This can cause problems with the organs normal function. Keeping the muscle strong can help prevent bladder control problems and unwanted urine leakage. FINDING THE PELVIC MUSCLE – Without tensing the muscles of your leg, buttocks or abdomen, imagine that you are trying to control the passing of gas or pinching off a stool. Or imagine you



are in an elevator full of people and you feel the urge to pass gas. What do you do? You tighten or pull in the ring of muscle around your rectum – your pelvic muscle. You should feel a lifting sensation in the area around the vagin* or a pulling in of your rectum. EXERCISE REGIMEN – There are two types of muscle contractions you will need to practice – Short (2 second) or Quick contractions and Slow (3 or 5 or 10 second) or long contractions. To do the short or quick muscle contractions, contract or tighten your pelvic muscle quickly and hard and immediately relax it. For the slow or long (sustained) contractions, contract or tighten your pelvic muscle and hold for a count of (3 or 5 or 10 as prescribed) seconds, then relax the muscle completely for the same amount of time. It is equally important to control when your muscle tightens and relaxes. Be sure to relax completely between each muscle tightening. WHERE TO PRACTICE – You should do the exercises in these positions: Lying Down – Lie on your back with your head on a pillow, knees bent and feet slightly apart. Sitting – Sit upright in a firm seat and straight-back chair, knees slightly apart, feet flat on the floor or legs stretched out in front and crossed at the ankles. Standing – Stand and lean on a back of a chair, knees slightly bent with feet shoulder width apart and toes slightly pointed outward. You can also lean on the kitchen counter with your hips flexed. PERFORMING THE “KNACK” – In addition to doing your prescribed set of pelvic muscle exercises, you should start contracting your pelvic muscle at the time your incontinence occurs. Timing your pelvic muscle contraction to when your incontinence is most likely to occur is called the “KNACK.” This is the skill of consciously timing an intentional contraction of the pelvic muscles just before and throughout the activity that causes an increase in your urine leakage (incontinence) or bladder control problem such as urgency. HOW TO DO THE “KNACK” – The “KNACK” is an acquired motor skill that requires you to anticipate your urine leakage. Any activity, which increases pressure in your abdomen, may cause you to lose urine. Examples of such activities are: coughing, sneezing, laughing, bending/ lifting, carrying objects, sitting down, standing up, and going up/down stairs. During these activities, pressure is placed on the bladder, forcing urine to leak out. You should practice the “KNACK” by contracting the pelvic floor muscles: † Immediately before initiating a hard cough and maintaining the contraction throughout the cough † Do 5 quick pelvic muscle contractions when you get a strong urge that you cannot control. † Tighten your muscle on the way to the bathroom. Remember, the more exercising you do: – The stronger your pelvic muscles will get. – The faster they will get stronger. – The easier it will be to maintain muscle strength. REMEMBER – It may take some time to translate the “KNACK” successfully into daily life. MAKING THE EXERCISES PART OF YOUR DAILY ACTIVITY – Once your muscles are stronger and you incontinence and urgency are better, you should do these exercises as part of your daily routine (activities you do on a daily basis). This means you do both types of exercises, short and long muscle contractions. You do not have to keep a formal count of the number of

Behavioral Treatments


times you do each exercise. Just do them several times in a row and often enough to make them a habit. Do your exercises when you are: † † † † †

Standing at the sink and brushing your teeth Sitting in the car at a stop light. Reading a book in bed. Going for a walk. Talking on the phone. YOU MUST PRACTICE SO THAT EXERCISING BECOMES A HABIT. ALMOST LIKE A REFLEX ACTION!!

# 2002 Diane K Newman

15 Pessaries and vagin*l Devices for Stress Incontinence G. Willy Davila and Minda Neimark Cleveland Clinic Florida, Weston, Florida, U.S.A.



Pessaries and other intravagin*l devices have long been used for the treatment of pelvic floor dysfunction in women. Initial descriptions of vagin*l device use entailed intravagin*l placement of objects to support genital prolapse and/or administer therapeutic chemicals. Specific applications of pessaries for women with stress urinary incontinence (SUI) are rather recent. Owing to the high coexistence of genital prolapse and urinary incontinence, it is likely that many women who were fit with a pessary for genital prolapse noted an improvement in their urinary incontinence. Alternatively, women with exteriorized prolapse may have occult stress incontinence which is uncovered upon being fit with a vagin*l pessary for reduction of the prolapse. The concept of intravagin*l device use as an option for SUI treatment is very useful for the practicing clinician. As our population ages, with an increased incidence of pelvic floor dysfunction, alternatives to surgery become more desirable. There are many urogynecologic indications for pessary usage (Table 1). In addition, technological developments have led to innovative designs of intravagin*l devices with specific purposes such as elevation of the urethrovesical junction (UVJ) (Fig. 1). To achieve continence, a device should provide elevation

Table 1 Indications for Pessary Use vagin*l and uterine prolapse Stress incontinence Patient unable to safely undergo pelvic reconstructive surgery Desire to delay surgery Evaluation of continence mechanism in moderate to severe vagin*l prolapse Preoperatively demonstrate effectiveness of urethropexy for SUI Pregnant patient with incompetent cervix/premature delivery/multiple gestation Genital prolapse in the neonate Low back/pelvic pain secondary to genital prolapse Postoperative usage following pelvic reconstructive surgery to prevent recurrence 267


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Figure 1 Intravagin*l devices specifically useful for enhancing bladder neck support: (a) Smith-Hodge pessary; (continued)

and support of the urethrovesical junction and/or extrinsically enhance urethral sphincteric function by compression. While doing this, outflow obstruction should be avoided to prevent significant urinary retention and its consequences.



Voiding difficulty, bladder outlet obstruction, and occult stress incontinence may coexist in a patient with severe prolapse. The initial descriptions of vagin*l pessary use for stress urinary incontinence were not in its therapy, but rather in the uncovering of occult stress incontinence in women with advanced degrees of prolapse (1). It was suggested that the mechanism of continence in women with severe prolapse is urethral obstruction, which increases maximum urethral closure pressure and pressure transmission ratio. It has been demonstrated that up to 70% of women with moderate to severe pelvic organ prolapse will demonstrate stress incontinence once the prolapse has been reduced (2 –5). Subsequently, Bhatia and colleagues described the impact of a Smith-Hodge pessary on urodynamic parameters in women with stress urinary incontinence (6). A pessary’s effect on urethral mobility and urodynamic parameters were described and noted to be similar to those of a successful bladder neck

Pessaries and vagin*l Devices


Figure 1 (b) Introl Bladder Neck Support Prosthesis; (continued)

suspension (Table 2). No evidence of urinary outflow obstruction was found. The use of SmithHodge pessaries for stress incontinence was popularized as a result of these data. A “pessary test” was suggested for identification of occult stress incontinence in women with advanced degrees of genital prolapse, and as a prognostic test for success of antiincontinence surgery—similar to a Bonney or Marshall test (7,8). Similarity in changes in continence mechanism with improvements in functional urethral length, urethral pressure profiles, and cough profiles was demonstrated in those who became asymptomatic with a pessary and those who underwent a Burch urethropexy. Smith-Hodge, Ring, and Gellhorn pessaries are most frequently used for this evaluation (2 –4,9). When using this test, care must be taken to avoid compressing the urethra and causing outflow obstruction. Smith-Hodge pessaries are especially useful for this purpose owing to the notched nature of the retropubic square end (Fig. 1a). Another practical feature of the Hodge pessary is the ability to modify its shape by folding it into a better-fitting device for an individual patient. The curvature of the pessary frequently requires shape adjustment in order to achieve a snug retropubic fit. Other intravagin*l devices have also been studied for the nonsurgical treatment of SUI. Contraceptive diaphragms, owing to their retropubic placement, may result in improved bladder neck support. In one study, complete resolution of SUI was reported in 91% of women fit with a diaphragm (10). Discomfort with the device in place led to discontinuation by 16% of the women. In addition, contraceptive diaphragms have been associated with the occurrence of urinary tract infections due to their effect on urethral outflow (11). Diaphragm fitting rings can also be effective in treating SUI in some women (12). Diaphragms and fitting rings may be useful in the patient with mild SUI and minimal prolapse. However, if significant prolapse is present or urine loss occurs with minimal exertion, diaphragms may not be strong enough to provide sufficient urethrovesical junction (UVJ) support. vagin*l tampons have also been used for SUI. Many women have reported that SUI is improved during menses when a tampon is in place. Tampons have been listed as effective


Davila and Neimark

Figure 1

(c) Continence Guard; (continued)

conservative options for the management of SUI (13). When compared to a Hodge pessary, a super tampon was found to be equally effective in reducing urine loss during an exercise session (14). In this study, the devices were used only during exercise sessions, and urodynamics was not performed. Thus, the author’s conclusions may not be applicable to many women with SUI. However, the wide availability and low cost of tampons make them an attractive first-line intravagin*l therapy for SUI. Importantly, extra-absorbent tampons should not be left in place for more than 6 h at a time in order to avoid the risk of toxic shock syndrome. Innovative devices specifically designed to elevate the bladder neck in a manner similar to a bladder neck suspension have recently been studied. The Introl Bladder Neck Support Prosthesis (BNSP) (Uromed Corp., Needham, MA) is available in the Far East but not widely used in the United States, despite approval by the FDA (Fig. 1b). It is a silicone ring-shaped device with two prongs at one end. Upon insertion, the prongs fit retropubically to provide

Pessaries and vagin*l Devices


Figure 1 (d) Continence Ring.

bladder neck support (Fig. 2). It was shown to reduce urine loss by 80% in most users with stress incontinence, with urodynamic effects similar to a bladder neck suspension (15). A multicenter study evaluating women with stress and mixed incontinence confirmed these findings (16). Fluoroscopic evaluation of a woman with a BNSP in place helps us understand the effect of a vagin*l device in enhancing bladder neck and proximal urethral support (Fig. 3). Its widespread use was limited by its cost and by the difficulties encountered in individualized fitting. Women who used the BNSP only during specific physical activities (i.e., jogging, tennis, etc.) were noted to be the most successful subgroup of users. A disposable intravagin*l device specifically designed to provide urethral support during exertion has been available in Europe. The Continence Guard is a single-use polyurethane foldable device (Fig. 1c). Thyssen and Lose showed that 95% of their study population were either dry or improved with the Continence Guard in place (17). Significant reduction in urine loss on a 24-h pad test, without alteration in uroflowmetry parameters, was noted (18). A multicenter study of this device revealed objective improvement in 75% of the study population, with 46% being dry on a pad test (19). Most recently, in the United Kingdom, a cylindrical vagin*l device designed to provide bladder neck support in women with stress incontinence has been marketed (Contiform, Bard Limited Forest House, West Sussex, U.K.). Its cylindrical design prevents its collapse during


Davila and Neimark

Table 2 Urodynamic Effects of Pessaries 1. 2. 3. 4. 5.

Enhance bladder neck support—normalize Q-tip angle Lengthen urethra—increase functional urethral length Enhance urethral sphincteric mechanism—increase urethral closure pressure Enhance urethral dynamic function—increase pressure transmission ratio Allow normal voiding—no effect on uroflow parameters

strenuous activities. It is reported to not cause outflow obstruction and results in continence in 85% of users (Bard Limited Forest House, data on file). Multiple other devices are being marketed for intravagin*l treatment of SUI. However, most have not undergone scientific study. Many commonly available pessaries have been modified by adding a “cushion” at one end to enhance urethral compression (Fig. 1d). Care must be taken to avoid urethral obstruction during usage.

Figure 2 Effect of intravagin*l device in bladder neck support—lateral view.

Pessaries and vagin*l Devices


Figure 3 Fluoroscopic appearance of intravagin*l device enhancing proximal urethral support.



In the 1800s, Hugh Lenox Hodge designed the lever pessary to treat uterine retroversion thought to be a cause of pelvic pain (20). As modifications of the lever pessary were made, other indications were proposed for its use. In 1961, Vitsky suggested that cervical incompetence was due to a lack of central uterine support. Uterine retroversion has also been associated with infertility and pelvic pain. Placing a lever pessary would displace the cervix posteriorly, thus lifting the weight of the uterus off of the incompetent cervix (21). Women diagnosed with an incompetent cervix were treated during pregnancy with a Hodge pessary from 14 to 38 weeks’ gestation, with an 83% successful pregnancy rate (22). Currently, cervical cerclage is the treatment of choice for women with cervical incompetence. There is great controversy regarding the possible causative role of uterine retroversion in many gynecologic conditions including pelvic pain, infertility, and sexual dysfunction.



Use of vagin*l devices for prolapse reduction and administration of chemicals is documented as far back as during the early Egyptian civilization. Written documentation of efforts to reduce genital prolapse with vagin*l objects dates back as far back as the fifth century. Modernization of the pessary came with the discovery of vulcanization of rubber and a better understanding of female anatomy. Since then, multiple modifications in pessary design and material selection for manufacture have been made (23). Advances in gynecologic surgery and anesthesia over the last several decades have reduced the need for pessary usage in the treatment of prolapse and incontinence. However, the recent increase in the elderly population requiring conservative treatment of prolapse and incontinence has led to a resurgence of pessary use (24). In addition, there remains a very acceptable role for therapeutic use of a vagin*l pessary in the premenopausal patient. In a recent survey administered to members of the American Urogynecologic Society, 77% of the


Davila and Neimark

respondents used pessaries as a first-line therapy for prolapse, and only 12% reserved pessaries for women who were not surgical candidates. In addition, 92% of the physicians surveyed believed that pessaries relieved symptoms associated with pelvic organ prolapse, and 48% felt they had a therapeutic benefit in addition to relieving the symptoms (25). In a simple prospective protocol for pessary management, patients with symptomatic pelvic prolapse were given the option of pessary use versus surgery or expectant management. If the vagin*l pessary was chosen as the method of treatment, the patient was fitted with a ring pessary or a pessary that could be retained without difficulty. The patient then followed up at scheduled intervals to evaluate pessary effectiveness. Sixty-six percent of those who used a pessary for .1 month remained users after 12 months. Fifty-three percent of the patients continued to wear the pessary after 36 months (26). A retrospective series of 107 patients who were fit with a Gellhorn, cube, or ring pessary for symptomatic vagin*l prolapse for various indications including medically unfit for surgery, awaiting surgery, or desired conservative management, confirmed that at least 50% of the women continued use of their pessary without complications at follow-up (27). Of those who continued pessary use, 20% were patients who initially desired surgery but later declined because of their satisfaction with the vagin*l pessary. At our center, pessaries are frequently used as first-line therapy for prolapse and incontinence. Review of our usage trends reveals rather equivalent use of the Smith-Hodge and Continence Ring pessaries for SUI. For advanced degrees of prolapse, our most commonly used pessary is the Gelhorn. Cube pessaries should only be used with extreme caution in women who will be compliant with follow-up, as the suctioned adherence to the vagin*l sidewalls may lead to significant mucosal erosions and ulcerations. A significant number of women who wear pessaries for SUI or prolapse eventually become frustrated with the efforts required for safe pessary use, and opt for surgical management.



Many different types of pessaries are available, most made of medical-grade silicone or rubber. Although the majority were designed for specific types of prolapse, clinical use is typically based on a “best fit” choice (Table 3). Whichever pessary is chosen, it must fit snugly without causing discomfort to the patient, allowing her to void easily. The health care provider must be prepared to try several different types and sizes until the correct pessary is found for each individual patient.



Clinicians may be hesitant to recommend pessary use by women with SUI. Various factors account for this reluctance. Owing to variations in pelvic anatomy, optimal fitting of a pessary may be challenging. In addition, the large number of pessary types, each with various sizes, further complicates the process. Because pessary fitting is a trial- and error-process, a clinician must have a large inventory of pessaries of varying sizes in order to accomplish appropriate fitting of patients. An appropriately fit pessary is comfortable, remains in place with ambulation, and allows for normal voiding. Pessary care recommendations should be followed closely for safe long-term use (Table 4). The patient who cannot self-care for the pessary must be seen by the clinician on a regular basis. We recommend scheduled office visits for pessary care every 6 weeks. Patients must be encouraged to use intravagin*l estrogen cream regularly. Some patients may be able to perform pessary self-care if removal is facilitated by attaching a string (dental floss or suture) to the pessary.

0–9 0–9 2–8 55 – 85 0 – 10 0–9 0–9 112 – 312 112 – 312 2 – 334 2 – 334 0–7

Smith-Hodge Risser Marland Incontinence Dish (mm) Incontinence Ring Ring (with or without support) Gerhrung (with or without knob) Gellhorn (inches) Schaatz (inches) Doughnut (inches) Inflatable (inches) Cube

Source: Ref. 23.


Pessary Types and Indications


Table 3








Vault prolapse

Stress incontinence

Pessaries and vagin*l Devices 275


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Table 4 Pessary Care Recommendations Remove at least two nights per week Leave out overnight Insert 1 – 2 g estrogen cream during night while pessary is out Wash pessary with soap and water Reinsert using water-soluble lubricant Report any unusual discharge, bleeding, or discomfort Report any changes in bladder or bowel function Have pelvic examination every 6 – 12 months Source: Ref. 23.

Cost issues must also be considered. In many cases, reimbursem*nt by insurance companies does not cover the entire cost of a pessary. Additionally, no optimal distribution systems through pharmacies or durable medical supply houses exist. The physician is thus typically at financial risk when fitting pessaries. Patients themselves may be hesitant to accept pessaries for SUI treatment. The common notion that pessaries are used solely by elderly women with prolapse and contraindications to surgical intervention frequently dissuades younger women from considering their use. Nevertheless, young women of reproductive age are often ideal candidates for pessary treatment of SUI (Table 5). VII.


Not all female candidates can be successfully fit with a pessary. Typical reasons for inability to be fit include vagin*l scarring with loss of vagin*l caliber or length from previous surgery, severe urogenital atrophy, vagin*l pain, and markedly restricted or enlarged vagin*l introitus. In women with restricted caliber, use of a vagin*l tampon may reduce stress incontinence. In those with significantly increased vagin*l caliber, performing a perineoplasty and subsequent refitting with a pessary should be considered. For elderly women with severe genital prolapse who are not, and will not become, sexually active, and cannot be fit with a pessary, consideration should be given to a colpocleisis performed under regional or local anesthesia. VIII.


Although the pessary can be a valuable tool in the treatment of stress incontinence and genital prolapse, there are certain patients for whom pessary use may be considered contraindicated (Table 6).

Table 5

Ideal Candidate for Pessary Usage for SUI

Reproductive age Comfortable with genital contact (i.e., tampon user) Adequate manual dexterity Usage primarily for specific activities (i.e., running) Compliant with safe usage recommendations Urethral hypermobility Well-estrogenized vagin* Unscarred vagin*

Pessaries and vagin*l Devices


Table 6 Contraindications to Pessary Use Severe atrophic tissues Erosive or ulcerative changes in the vagin*l mucosa Inability to remove pessary on a regular basis Undiagnosed vagin*l bleeding Undiagnosed vagin*l discharge vagin*l or cervical cancer Noncompliance in follow-up Impaired mental capacity



The concept of using an intravagin*l device for treatment of stress incontinence is attractive to many women suffering from stress urinary incontinence. Various devices specifically designed to provide bladder neck support during exertional activities have been developed and proven to be effective. Motivated patients who wish to avoid surgical therapy are the optimal candidates for vagin*l pessary use. Although several limiting factors may arise, including difficulty with insertion and removal, interference with sexual activity, pelvic discomfort, and associated vagin*l discharge, vagin*l devices are a valuable conservative option for the treatment of stress incontinence.



4. 5. 6. 7. 8. 9. 10. 11. 12.

Richardson DA, Bent AE, Ostergard DR. The effect of uterovagin*l prolapse on urethrovesical pressure dynamics. Am J Obstet Gynecol 1983; 146:901– 905. Bergman A, Koonings PP, Ballard CA. Predicting postoperative urinary incontinence development in women undergoing operation for genitourinary prolapse. Am J Obstet Gynecol 1988; 158:1171– 1175. Veronikis DK, Nichols DH, Wakamatsu MM. The incidence of low-pressure urethra as a function of prolapse-reducing technique in patients with massive pelvic organ prolapse (maximum descent at all vagin*l sites). Am J Obstet Gynecol 1997; 177:1305 –1314. Rosenzweig BA, Pushkin S, Blumenfeld D, Bhatia NN. Prevalence of abnormal urodynamic test results in continent women with severe genitourinary prolapse. Obstet Gynecol 1992; 79:539 – 542. Chaikin DC, Groutz A, Blaivas JG. Predicting the need for anti-incontinence surgery in continent women undergoing repair of severe urogenital prolapse. J Urol 2000; 163:531 – 534. Bhatia NN, Bergman A, Gunning JE. Urodynamic effects of a vagin*l pessary in women with stress urinary incontinence. Am J Obstet Gynecol 1983; 147:876– 884. Bhatia NN, Bergman A. Pessary test in women with urinary incontinence. Obstet Gynecol 1985; 65:220– 226. Bergman A, Bhatia NN. Pessary test: simple prognostic test in women with stress urinary incontinence. Urology 1984; 24:109 – 110. Romanzi LJ, Chaikin DC, Blaivas JG. The effect of genital prolapse on voiding. Urology 1999; 161:581– 586. Suarez GM, Baum NH, Jacobs J. Use of standard contraceptive diaphragm in the management of stress urinary incontinence. Urology 1991; 37:119 – 122. Fihn SD, Johnson C, Pinkstaff C, Stamm WE. Diaphragm use and urinary tract infections: analysis of urodynamic and microbiological factors. J Urol 1986; 136:853– 856. Realini JP, Walters MD. vagin*l diaphragm rings in the treatment of stress urinary incontinence. J Am Board Fam Pract 1990; 3:99 – 103.

278 13. 14. 15. 16. 17.


19. 20. 21. 22. 23. 24. 25. 26. 27.

Davila and Neimark Marshall S. Conservative management of stress urinary incontinence [letter]. Urology 1991; 38:294. Nygaard I. Prevention of exercise incontinence with mechanical devices. J Reprod Med 1995; 40:89– 94. Davila GW, Ostermann KV. The bladder neck support prosthesis: a nonsurgical approach to stress incontinence in adult women. Am J Obstet Gynecol 1994; 171:206 – 211. Davila GW, Neal D, Horbach N, Preacher J, Doughtie JD, Karram M. A bladder neck support prosthesis for women with stress and mixed incontinence. Obstet Gynecol 1999; 93:938 –942. Thyssen HH, Lose G. Long term efficacy and safety of a disposable vagin*l device (Continence Guard) in the treatment of female stress incontinence. Int Urogyn J Pelvic Floor Dysfunct 1997; 8:130– 133. Thyssen H, Lose G. New disposable vagin*l device (Continence Guard) in the treatment of female stress incontinence. Design, efficacy and short-term safety. Acta Obstet Gynaecol Scand 1996; 75:170– 173. Hahn I, Milsom I. Treatment of female stress urinary incontinence with a new anatomically shaped vagin*l device (Conveen Continence Guard). Br J Urol 1996; 77:711 – 715. Miller DS. Contemporary use of the pessary. In: Sciarra JJ, ed. Gynecology and Obstetrics. Vol 1. Philadelphia: Lippencott-Raven, 1992:1– 12. Vitsky M. Simple treatment of the incompetent cervical os. Am J Obstet Gynecol 1961; 81:1194– 1197. Oster S, Javert CT. Treatment of the incompetent cervix with the Hodge pessary. Obstet Gynecol 1966; 28:206 –208. Davila GW. vagin*l prolapse: management with nonsurgical techniques. Postgrad Med 1996; 99:171– 176, 181, 184–185. Poma PA. Nonsurgical management of genital prolapse: a review and recommendations for clinical practice. J Reprod Med 2000; 45:789 – 797. Cundiff GW, Weidner AC, Visco AG, Bump RC, Addison WA. A survey of pessary use by members of the American Urogynecologic Society. Obstet Gynecol 2000; 95:931 – 935. Wu V, Farrell SA, Baskett TF, Flowerdew G. A simplified protocol for pessary management. Obstet Gynecol 1997; 90:990 – 994. Sulak PJ, Kuehl TJ, Shull BL. vagin*l pessaries and their use in pelvic relaxation. J Reprod Med 1993; 38:919 –923.

16 Current Role of Transvagin*l Needle Suspensions Firouz Daneshgari The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.



The modern era of surgical treatment of stress urinary incontinence (SUI) began in 1892 when Poussan (1) proposed the concept of urethral meatus advancement, and it followed an amazing and sometimes convoluted path through the 20th century. Transvagin*l needle suspension (TVNS) was introduced in the 1950s as a simpler and less invasive treatment for SUI in women.



In 1959, Armand Pereyra (2) introduced a novel approach to surgical treatment of the patient with genuine SUI. His decision on switching from the traditional MarshallMarchetti-Krants procedure was based on the failure of cases he observed, which he attributed to “strands of fibrous material between the relaxed tissues and the posterior aspects of the symphysis.” Therefore, he postulated that if the tissues could be suspended from the rectus fascia, traction from coughing and Valsalva maneuver would not encourage disruption of the repair. Pereyra devised the principle of the needle suspension with the design of a ligature carrier. His first published results reported 28 successful procedures and two failures. In 1973, Thomas Stamey (3) from California described several modifications of the needle suspension. The main revision was the use of cystoscopy to determine the position of the bladder neck with accuracy and hence to place the sutures in close proximity to this point. In 1979, Shlomo Raz (4), from the University of California at Los Angeles, reported a modification of the Pereyra procedure using a curvilinear incision and including the paravagin*l tissues within the helical suture. Cobb and Radge (5), in 1978, suggested the use of a double-pronged needle passer in order to reduce the number of passages of a needle through the tissue. In 1989, Raz et al. (6) also described the “four-corner suspension”—a TVNS operation that repairs anterior vagin*l wall prolapse in addition to producing an anti-incontinence effect due to its ability to place the bladder neck in the high retropubic position. 279





Regardless of the specific modifications, the general principles of the needle suspension remain the same. These include suspension/elevation of the bladder neck and of the proximal urethra (by vagin*l wall or synthetic material) by use of a nonabsorbable suture. The details of surgical techniques of various TVNS are discussed in another chapter.



No discussion on the assessment of a treatment option for UI could be complete without a discussion on the issue of level of evidence. The evidence required in the medical literature is limited to data reported in clinical trials, specifically excluding expert opinion. This is similar to that required to determine the final judgment of a jury in a legal proceeding, which must be based on the material evidence presented during the trial. The judgment (opinion) of the jury is not evidence. Evidence is factual information presented. Attempts to find such evidence have led several national and international organizations to conduct exhaustive searches of the literature with the aim of providing some guidelines to clinicians for UI management. In this regard, four documents have been released over the past decade: 1. 2. 3.

AHCPR’s Clinical Practice Guideline reports on UI in adults in 1992 and 1996 (7). The report of the AUA Clinical Guidelines Panel on surgical management of female SUI (8). The report of the World Health Organization First and Second International Consultations on Incontinence (ICI) (9,10).

All these documents were based on a review of the existing literature by panels of experts who subsequently formulated the recommendations. The AHCPR Report and ICI addressed the issue of data quality by dividing the level of evidence into High (or A) Best: where the recommendation is supported by scientific evidence from properly designed and implemented controlled trials providing statistical results that consistently support the panel’s recommendation; Intermediate (or B) Acceptable: where the recommendations are supported by scientific evidence from properly designed and implemented clinical series that support the guideline statement; and Low (or C) Marginal: the recommendation is supported by expert opinion.



In 1997, the AUA Female Stress Urinary Incontinence Clinical Guidelines Panel published guidelines for the surgical treatment of stress incontinence (8). The AUA report on surgical management of female SUI was based on a final review of 282 articles by a selected panel of experts that included treatment outcome reports in clinical trials including nonrandomized controlled trials. Four major surgical techniques were studied: retropubic suspensions, transvagin*l suspensions, anterior repairs, and sling procedures. The following criteria were reviewed in these trials: cure/dry, cure/dry/improved postoperative urgency, retention, hospital days, resumption of normal activities, transfusion, general conservative complications, intraoperative complications, preoperative complications, subjective complications, and complications requiring surgery. Based on this review, the panel concluded that (a) retropubic

Transvagin*l Needle Suspensions


suspensions and slings are the most efficacious procedures for long-term success on the basis of cure/dry rates, but (b) retropubic suspensions and sling procedures are associated with slightly higher complication rates (including postvoiding dysfunction) and with a longer convalescence, and (c) anterior repairs are the least likely to be efficacious over time. The level of evidence for the AUA guidelines recommendation was “Low (or C) Marginal” by ICI’s and AHCPR’s guidelines. Despite that, however, these recommendations have encouraged many urologists in the United States to use the sling as the primary procedure for stress incontinence. This trend is illustrated clearly by comparing the results of two surveys in which American urologists were asked what procedure they used for stress incontinence related to urethral hypermobility. In the 1996 report, 71% of urologists used needle suspensions and 25% used retropubic suspensions (11). In the 2001 report, 38% of urologists used needle suspensions, 16% used retropubic suspensions, and 44% used slings for type I stress incontinence; for type II stress incontinence, the corresponding numbers were 14%, 17%, and 68%, respectively (12).



The reported incidence of de novo detrusor instability following needle suspensions has varied between zero and 20%, with a mean incidence in the region of 5.8%. Voiding disorders may also follow this procedure, with a mean of 5.8% and a range of 1 – 24% (13).



One of the historical attractions of the TVNS was the minimally invasive advantage they had over the alternatives of retropubic suspensions and pubovagin*l slings. In addition, urologists and gynecologists were originally taught to use retropubic or needle suspensions if the patient had urethral hypermobility or anatomical incontinence. Sling operations were reserved for cases of intrinsic urethral sphincter deficiency because they had higher morbidity. However, with the improved understanding of the pathophysiology of SUI, we now believe that it is the hammock support of the bladder neck or the urethra and not the intrapelvic position of the urethra that helps the SUI. The surgical consequence of this enhanced understanding is that the surgeons no longer pull the slings with tension. Moreover, with improved techniques, suture material, and availability of allograft fascia, the morbidity of sling procedures has decreased significantly (14,15). The combination of a low rate of long-term cure by TVNS, decreased morbidity, and the ease of performing pubovagin*l sling procedures has increasingly created a situation where the use of TVNS as a primary treatment option for even simple SUI is rapidly decreasing.

REFERENCES 1. 2. 3. 4.

Poussan. Arch Clin Bord 1892; 1. Pereyra AJ. A simplified surgical procedure for the correction of stress urinary incontinence in women. West J Obstet Gynecol 1959; 67:223 – 226. Stamey TA. Cystoscopic suspension of the vesical neck for urinary incontinence. Surg Gynecol Obstet 1973; 136:547– 554. Raz S. Modified bladder neck suspension for female stress incontinence. Urology 1981; 17:82 –85.

282 5. 6. 7.


9. 10. 11. 12. 13. 14. 15.

Daneshgari Cobb OE, Radge H. Simplified correction of female stress incontinence. J Urol 1978; 141:38 – 42. Raz S, Klutke CG, Golomb J. Four-corner bladder and urethral suspension for moderate cystocele. J Urol 1989; 142(3):712– 715. Clinical Practice Guideline: Urinary Incontinence in Adults: Acute and Chronic Management. U.S. Department of Health and Human Services. Public Health Service, Rockville, MD. Agency for Health Care Policy and Research, 1996; AHCPR publication No. 96-0682. Leach GE, Dmochowski RR, Appell RA, Blaivas JG, Hadley HR, Luber KM, Mostwin JL, O’Donnell PD, Roehrborn CG. Female Stress Urinary Incontinence Clinical Guidelines Panel. Summary report on surgical management of female stress urinary incontinence. J Urol 1997; 158(3 Pt 1):875 – 880. Abrams P, Khoury S, Wein A, eds. Incontinence. First International Consultation on Incontinence, Monaco, July 28 –July 1, 1988. Abrams P, Carduzo L, Khoury S, Wein A, eds. Incontinence. 2nd International Consultation on Incontinence, Paris, July 1 – 3, 2001. Gee WF, Holtgrewe HL, Albertsen PC. Practice trends of American urologists in the treatment of impotence, incontinence and infertility. J Urol 1996; 156:1778 – 1782. Kim HL, Gerber GS, Patel RV. Practice patterns in the treatment of female urinary incontinence: a postal and Internet survey. Urology 2001; 57:45– 48. Jarvis FJ. Surgery for genuine stress incontinence. Br J Obstet Gynaecol 1994; 101:371 –373. Chaikin DC, Rosenthal J, Blaivas JG. Pubovagin*l fascial sling for all types of stress urinary incontinence: long-term analysis. J Urol 1998; 160:1312– 1316. Barnes NM, Dmochowski RR, Park R, Nitti VW. Pubovagin*l sling and pelvic prolapse repair in women with occult stress urinary incontinence: effect on postoperative emptying and voiding symptoms. Urology 2002; 59(6):856– 860.

17 Anterior vagin*l Wall Suspension Tracey Small Wilson and Philippe E. Zimmern University of Texas Southwestern Medical Center, Dallas, Texas, U.S.A.



Raz described the first four-corner bladder and urethral suspension procedure in 1989 (1). He recognized that many anti-incontinence procedures failed because they addressed anterior vagin*l wall prolapse or urethral hypermobility rather than addressing the two together. For example, the Kelly-type plication corrected the cystocele by reapproximation of the pubocervical fascia, but it was associated with a high failure rate for stress urinary incontinence (SUI) (50 –80%) (2) partly because it did not support the proximal urethra and bladder neck. Conversely, the Marshall-Marchetti-Krantz (MMK) bladder neck suspension corrected urethral hypermobility but not the cystocele. Raz believed that bladder base descent and urethral hypermobility must be corrected at the time of cystocele repair regardless of whether incontinence existed. At that time, the only procedure accomplishing this combined goal was the retropubic Burch cystourethropexy. Raz therefore drew from his experience with the modified Peyrera needle suspension procedure to develop a vagin*l technique that would simultaneously address urethral hypermobility and anterior vagin*l wall prolapse. Raz’s original modification of the Pereyra suspension procedure incorporated the urethropelvic ligament, pubocervical fascia, and vagin*l wall (without its epithelium) into helical suspensory sutures (3). He further modified this procedure to develop the four-corner bladder neck suspension (1). By combining this initial set of helical sutures (placed at the bladder neck) with a second set (placed at the level of the cystocele base), Raz created four sites, or “corners,” from which the proximal urethra and bladder base were suspended. Via an inverted U-shaped incision, these nonabsorbable sutures were placed very lateral (as with the Burch suspension) to minimize the risk of outflow obstruction. They were then transferred suprapubically by a ligature carrier and secured to the anterior rectus fascia. This procedure essentially resuspended the anterior vagin*l wall without repairing the fascial defect. In his initial series of 120 patients with grade 2 or 3 cystocele Raz reported a 94% and 98% subjective correction of incontinence and cystocele, respectively. Obstruction was relieved in 84% of patients, preoperative detrusor instability improved in 54%, and de novo urge occurred in 5% (1). Despite these successes, patients continued to experience a significant amount of suprapubic discomfort and cystocele recurrence. Bruskewitz et al. compared several different anchoring materials and their rate of tissue pull through and local tissue reaction in the rabbit abdominal wall (4). He concluded that loops of suture 283


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material had a lower incidence of tissue pull-through and tension loss over time. He believed this was due to a lower initial tension and a greater cross-sectional area of the anchor material. Using Bruskewitz’s findings, Leach and Zimmern modified the Raz four-corner suspension to obtain a broader anterior vagin*l wall anchor (5). They believed that broader support of the upper vagin* would protect the bladder neck repair and distribute pressure more evenly during stress maneuvers. Their distal sutures were placed in the vagin*l wall at the bladder neck level and did not incorporate the urethropelvic ligaments. Proximal sutures were placed in a helical fashion at the cystocele base to provide broader and stronger support of the upper anterior vagin*l wall. If the uterus was present, these helical sutures incorporated the cardinal ligaments; if absent, they incorporated the scar of the vagin*l cuff. Long-term results of the four-corner procedure were reported in 1997 (6). Using both subjective and objective outcomes, Dmochowski et al. (6) evaluated 47 patients after a mean of 37 months (range 15– 80 months) and found an 87% subjective cure or improvement rate. Standing voiding cystourethrogram revealed recurrent cystocele, grade I or II (Baden-Walker classification) (7), in 57%. This moderate recurrence rate was attributed to possible suture pullthrough from the cardinal ligament complex or apical cuff. Upon more careful evaluation of those patients with recurrent cystoceles, the recurrent fascial defect was found to be centrally located. Further modifications were therefore imposed. The current procedure, described below, is referred to as an anterior vagin*l wall suspension (AVWS).



The AVWS is indicated in patients diagnosed with SUI due to urethral hypermobility and a small to moderate cystocele (grade I or II) with no midline fascial defect, as seen on voiding cystogram (VCUG). Upper vagin*l suspension sutures support and elevate the cystocele base, while the distal sutures support the bladder neck, thereby correcting urethral hypermobility. Patients with large cystoceles (grade III or IV) due to a central defect are best served with an anterior colporrhaphy or an abdominal sacrocolpopexy along with support of the bladder neck (8). The AVWS is not indicated in patients with SUI due to intrinsic sphincteric deficiency (ISD) alone, and no urethral hypermobility. This procedure does not provide sufficient urethral coaptation to ensure dryness in this population. If the patient has a cystocele in association with ISD (as diagnosed by physical examination and urodynamics), a pubovagin*l sling along with support of the upper anterior vagin* or an anterior colporrhaphy is indicated depending, on the extent of the cystocele. Simultaneous correction of the cystocele is indicated to avoid excessive angulation at the urethrovesical junction, which could produce outflow obstruction.



After induction of general anesthesia, the patient is placed in the high dorsal lithotomy position using candy-cane stirrups. The lower abdomen, perineum, and vagin* are properly prepped and draped, and a ring retractor is positioned to aid visualization. A urethral catheter is inserted, and the balloon is palpated to identify and mark the bladder neck. Marking sutures are now placed at the vagin*l apex—one in the midline and one 1.5 cm lateral to the midline on each side. Beginning 1.5 cm lateral to the bladder neck, an incision is made in the anterior vagin*l wall and extended proximally to the level of the marking sutures—lateral to the cervix or to the vagin*l apex. The same procedure is repeated on the opposite side (Fig. 1). The area of anterior vagin*l wall between the incision lines will serve as the elevating vagin*l wall plate and is

Anterior vagin*l Wall Suspension


Figure 1 Initial setup of AVWS. Three marking sutures are placed at vagin*l apex. Bilateral anterior vagin*l incisions are made extending from the level of the bladder neck to the vagin*l cervix or cuff.

usually 3 cm in width and 4 –8 cm in length depending upon the length of the anterior vagin*l wall (average 6 cm). In the presence of a moderate cystocele, the redundant vagin*l wall lateral to these incisions should be excised lengthwise, preserving 0.5 –1 cm of tissue laterally in order to recreate the lateral sulcuses upon closure of the vagin*l wall. The 3 4 –8 cm in situ anterior vagin*l wall plate is now divided into equal quadrants using a marking pen. The first of four No. 1 polypropylene sutures is placed into the scar of the vagin*l cuff or cardinal ligament and run distally in a helical fashion to the level of the midvagin* (half the length of the vagin*l plate). The helical bites should traverse medially to the middle of the vagin*l plate and should incorporate the vagin*l wall, excluding the epithelium. The second suture is then placed at the level of the midvagin* and run distally by two to three helical passes to the bladder neck area (Fig. 2). The third and fourth sutures are placed similarly on the opposite side. A 3 – 4 cm transverse suprapubic incision is then made two fingerbreadths above the level of the pubic symphysis and carried down to the level of the rectus fascia. This incision should be as close to midline as possible to avoid genitofemoral nerve involvement. Owing to the risk of bleeding, placement of the four suspension sutures and suprapubic incision are done before entering the retropubic space. Blunt or sharp dissection at the level of the bladder neck is now performed to develop the plane laterally between the endopelvic fascia and the pubic bone. Once this space is cleared of all adherent tissue, the deep endopelvic fascia is perforated, which allows entrance into the retropubic space. The retropubic space is then developed anteriorly using a sweeping motion of the finger along the inside surface of the pubic bone. It is critical to keep the catheter on gravity drainage to ensure bladder emptiness during this maneuver. In a virgin case, there is little to no resistance entering the retropubic space at the site of the lateral defect. However, after a Burch or MMK procedure, there may be a significant amount of


Wilson and Zimmern

Figure 2 Placement of suspension sutures. Note division of vagin*l plate into quadrants. PS, proximal sutures; DS, distal sutures.

retropubic scarring, which increases the risk of bladder injury during finger dissection or needle passage. Once it is felt that only rectus fascia and muscle remain between a finger in the suprapubic incision and one in the retropubic space, each of the four suspension sutures is transferred to the suprapubic position using a ligature carrier. We use a double-pronged ligature carrier; however, a single pronged instrument may be necessary in obese patients or in those with significant abdominal wall and/or retropubic scarring. When possible, the proximal suspension sutures (adjacent to cervix) are placed more lateral and cephalad than the distal suspension sutures (Fig. 3). After intravenous indigo carmine is given, cystoscopy with a 708 lens is performed to exclude intravesical suture placement and/or bladder perforation and to confirm ureteral integrity. If sutures are present in the bladder, they should be removed via the vagin*l side and repositioned. A large bladder perforation should be closed in multiple layers immediately with possible interposition of a fat graft (9) (in this instance, the anti-incontinence procedure may need to be aborted). The vagin*l wall incisions are now closed with running 2-0 absorbable suture. Using a rubber-shod right-angle clamp, each suture is grasped 1.5 –2 cm above the rectus fascia and tied above the clamp as an assistant supports the vagin*l plate in a position parallel to the floor. This maneuver provides adequate support without over correction. An antibiotic-soaked vagin*l pack is inserted, and the suprapubic incision is closed.



Both subjective and objective outcome measures have been used to assess effectiveness of the AVWS. Lemack and Zimmern reported midterm results of the AVWS in 61 of 102 women who

Anterior vagin*l Wall Suspension


Figure 3 Final appearance of suspension sutures. Note that sutures cover the entire vagin*l plate. Proximal sutures (PS) are placed more lateral and cephalad than distal sutures (DS).

had responded to questionnaires at a mean of 25 months following AVWS (10). Seventy-seven percent of patients were subjectively cured or improved of their stress incontinence. Using a visual analog scale and the quality-of-life question—“If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?”—the median preoperative score was 6.7 (0, pleased; 10, terrible), and declined postoperatively to a median response of 2. Eight percent experienced de novo urge incontinence, and diuretic use was the only poor prognostic indicator. The standing voiding cystourethrogram (VCUG) has been used as an objective outcome tool for anti-incontinence procedures (11). Showalter et al. (12) compared the VCUG of 76 continent control patients to two surgical groups: group 1, 52 patients who underwent an AVWS for urethral hypermobility and grade I or II cystocele; group 2, 36 patients with grade III or greater cystocele who underwent formal anterior colporrhaphy. After 3 –6 months, there was no difference in the urethral angle in patients who had undergone the AVWS compared to controls. There was also a significant reduction in the lateral height of the cystocele following AVWS and anterior colporrhaphy (Figs. 4, 5).


Wilson and Zimmern

Figure 4 Preoperative lateral VCUG demonstrating urethral hypermobility (urethral angle of 60 – 708) associated with a mild cystocele.

Sexual function following AVWS has also been assessed. Lemack and Zimmern subjectively evaluated 93 women at least 1 year following an AVWS alone or in combination with a posterior colporrhaphy (13). Sixty percent of patients responded to a mailed questionnaire. The same percentage of patients was sexually active postoperatively as preoperatively; however, only 20% noted dyspareunia postoperatively, compared to 29% preoperatively. Eighteen percent of patients reported intercourse to be worse postoperatively, but these were not the same patients who reported dyspareunia. Thus, the etiology of this finding remains unclear. Only one of 29 patients who had undergone an AVWS alone reported sexual inactivity due to loss of libido or inability to have intercourse. The AVWS did not seem to adversely affect the majority of women who were sexually active, and the incidence of symptomatic vagin*l narrowing was rare. Other investigators have also utilized the anterior vagin*l wall in anti-incontinence procedures. Appell described the in situ vagin*l wall sling, which utilizes the anterior vagin*l wall for support of the proximal urethra and bladder neck (14). This vagin*l wall support is

Anterior vagin*l Wall Suspension


Figure 5 Postoperative lateral VCUG demonstrating a normal urethral angle and a well-supported bladder base.

anchored to the pubic bone, thereby limiting the amount of retropubic dissection. Kaplan also described his long-term results with the vagin*l wall sling (15). The AVWS is not a sling procedure but does utilize the vagin*l wall as a supporting structure. There are many advantages to using the anterior vagin*l wall in anti-incontinence procedures. Namely, it does not require a separate harvesting incision (as is necessary for autologous fascia); one avoids the risk of tissue contamination and disease transmission that is a small but potential risk with allograft and xenograft materials; and there is less risk of infection and erosion than is seen with synthetic materials. The AVWS most resembles the Burch bladder neck suspension, which has recognized durability and effectiveness in correcting stress urinary incontinence due to urethral hypermobility. A recent meta-analysis found the Burch procedure to be 85% successful after 4 years (16). Like the Burch procedure, support of the AVWS is based on a broad vagin*l anchor. The retropubic dissection common to both procedures promotes scarring in this region, which further enhances the vagin*l support. The vagin*l support in the Burch procedure is anchored to


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Cooper’s ligament, whereas the anchoring point for the AVWS is the rectus muscle tendon as it inserts into the back of the pubic symphysis. The transvagin*l approach for the AVWS allows repair of concomitant pelvic prolapses through the same incision. In addition, lack of a Pfannenstiel incision reduces postoperative incisional pain and allows for a shorter convalescence following the AVWS.



The AVWS procedure is a reliable surgical option for the patient with stress urinary incontinence due to urethral hypermobility in the presence of a small to moderate cystocele. It is favorable to the patient due to its shortened convalescence and reduced postoperative morbidity. From a surgeon’s perspective, it is easy to teach and reproducible. Midterm results of the AVWS are respectable, and its long-term results are forthcoming.


3. 4. 5. 6.

7. 8. 9. 10. 11. 12. 13. 14. 15.


Raz S, Klutke C, Golomb J. Four-corner bladder and urethral suspension for moderate cystocele. J Urol 1989; 142:712– 715. Stanton SL, Hilton P, Norton C, Cardozo L. Clinical and urodynamic effects of anterior colporrhaphy and vagin*l hysterectomy for prolapse with and without incontinence. Br J Obstet Gynaecol 1982; 89:459– 463. Raz S. Modified bladder neck suspension for female stress incontinence. Urology 1981; 17:82 –85. Bruskewitz RC, Nielsen KT, Graversen PH, Saville WD, Gasser TC. Bladder neck suspension material investigated in a rabbit model. J Urol 1989; 142:1361– 1363. Zimmern PE, Leach GE, Sirls L. Four-corner bladder neck suspension. In: Leach GE, ed. Atlas of the Urologic Clinics of North America. Philadelphia: W.B. Saunders, 1994:29– 36. Dmochowski RR, Zimmern PE, Ganabathi K, Sirls GL, Leach GE. Role of the four-corner bladder neck suspension to correct stress incontinence with a mild to moderate cystocele. Urology 1997; 49:35– 40. Baden WF, Walker TA. Surgical Repair of vagin*l Defects. Philadelphia: J.B. Lippincott, 1992. Miyazaki FS, Miyazaki DW. Raz four corner suspension for severe cystocele: poor results. Int Urogynecol J Pelvic Floor Dysfunc 1994; 5:94– 97. Hernandez RD, Himsl K, Zimmern PE. Transvagin*l repair of bladder injury during vagin*l hysterectomy. J Urol 1994; 152:2061– 2062. Lemack GE, Zimmern PE. Questionnaire-based outcome after anterior vagin*l wall suspension for stress urinary incontinence (abstract). J Urol 2000; 163(4):73. Zimmern PE. The role of voiding cystourethrography in the evaluation of the female lower urinary tract. Prob Urol 1991; 5:23 – 41. Showalter PR, Zimmern PE, Roehrborn CG, Lemack GE. Standing cystourethrogram: an outcome measure after anti-incontinence procedures and cystocele repair in women. Urology 2001; 58:33– 37. Lemack GE, Zimmern PE. Sexual function after vagin*l surgery for stress incontinence: results of a mailed questionnaire. Urology 2000; 56:223 –227. Appell RA. In situ vagin*l wall sling. Urology 2000; 56:499 – 503. Kaplan SA, Te AE, Young GP, Andrade A, Cabelin MA, Ikeguchi EF. Prospective analysis of 373 consecutive women with stress urinary incontinence treated with a vagin*l wall sling: the Columbia – Cornell University experience. J Urol 2000; 164:1623 –1627. Leach GE, Dmochowski RR, Appell RA, Blaivas JG, Hadley HR, Luber KM, Mostwin JL, O’Donnell PD. Report on the Surgical Management of Female Stress Urinary Incontinence Clinical Practice Guidelines. Baltimore: American Urological Association, 1997.

18 Retropubic Urethropexy Jeffrey L. Cornella Mayo Clinic Scottsdale, Scottsdale, Arizona, U.S.A.



The suprapubic approach to anterior segment or urethrovagin*l stabilization is known as retropubic urethropexy. Retropubic urethropexy (RPU) procedures have a long and important history in pelvic surgery. They remain an essential contribution to the surgical armamentarium for the management of female urinary incontinence. This chapter will review the history, techniques, and pertinent literature of the retropubic urethropexies—open and laparoscopic.



The past several years have seen an increasing trend for selection of the pubovagin*l sling as a primary incontinence procedure in the United States. There were two phenomena that accelerated this trend. The first was accumulating data on the poor outcomes of needlesuspension procedures. The second was the development of a less invasive pubovagin*l sling, in the form of the transvagin*l tape procedure (TVT) (1). Additionally, the misconception of intrinsic sphincteric deficiency as an entity with a possible laboratory diagnosis further resulted in increased numbers of patients receiving slings. Practice trends may reach the point where the majority of patients are simply relegated to a TVT procedure, with little clinical evaluation or attention to paravagin*l anatomy. Caution should be exhibited prior to relegating all patients to TVT-like procedures. First of all, the strong objective data on TVT procedures only extends 5–7 years (2). The Burch urethropexy has 10- to 20-year objective data in several studies showing a high cure rate for stress urinary incontinence (3 – 5). It is unclear how the TVT will perform at 10 years plus compared to other procedures, especially if stretching of the sling material occurs. Additionally, the TVT only supports the urethra, and if the patient has a paravagin*l defect, which is often the case, the patient would be best served with a site-specific repair of the paravagin*l area and retropubic urethropexy. If this is not done, the patient may continue to show anterior wall descent and additional symptoms.




The majority of patients with low urethral pressures or low Valsalva leak-point pressures are candidates for urethropexy, as the subsequent section on patient selection in this chapter will emphasize.



In many respects the retropubic urethropexy was introduced in the United States by the work of George Reaves White (6). White studied anatomy under Josef Halban in Vienna, just after the turn of the 20th century. The 1909 and 1912 articles regarding a radical cure for cystocele by White documented both a vagin*l and an abdominal approach to the anterior segment (6,7). The anterior approach was a retropubic vaginopexy in the form of a paravagin*l defect repair (PVDR). The anterior sulcus of the vagin*l was reattached to the appropriate anatomic site, the arcus tendineus fascia pelvis (ATFP). This technique was lost for decades until its resurrection by the work of A. Cullen Richardson in the late 1970s. In the interim, 30 years before the articles of Richardson, a different procedure for fixation of the urethra was described. This procedure was not a site-specific repair, but rather fixed the urethra to the posterior symphysis and disregarded the anterior lateral sulcus. Marshall et al. reported their female incontinence procedure in 1949 (8). Thousands of women have since received the Marshall-Marchetti-Krantz (MMK) procedure and its modifications for the control of urinary stress incontinence. It consists of fixation of the urethra and bladder by a bilateral series of three chromic sutures to the periosteum of the symphysis.

Figure 1 Tied paravagin*l sutures attaching anterior lateral sulcus of vagin* to obturator internis muscle along the white line (ATFP). (Used with permission of John Miklos.)

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A patient who did not receive this intended procedure because of a weak periosteum was responsible for precipitating a new point of attachment and thus a different retropubic urethropexy. The operating surgeon was John Christopher Burch, and he chose as a new site of attachment, the iliopectineal ligament of Cooper (9). This procedure, performed in 1958, eventually became known as the Burch procedure. It would become the gold standard of the retropubic urethropexies. It has the largest literature and greatest long-term follow-up of any operation for female urinary incontinence. It is often the Burch procedure that other techniques for urinary incontinence are compared to in randomized studies. It will be the main procedure emphasized in this chapter, given the strong foundation of underlying literature.




Paravagin*l Defect Repair

The anterior lateral sulcus of the vagin* is normally attached to the arcus tendineus fascia pelvis and portions of the levator musculature. The majority of anterior compartment defects, which are often referred to as cystoceles, are related to detachment and separation of this anatomic site (10). Restoration of the anatomy via the abdomen offers a symmetrical and complete repair without potentially inducing neuropathy by penetration of the urogenital diaphragm. It is a site-specific repair that often results in the cure of female urinary stress incontinence. A series of sutures attach the anterior lateral sulcus to the ATFP or white line of the obturator internis muscle. It is not considered a standalone incontinence operation used by the majority of surgeons who treat female urinary stress incontinence, owing to a lack of prospective studies documenting its efficacy. The single prospective study that compared the PVDR to the Burch procedure for the treatment of female urinary incontinence showed a significantly higher failure rate in those patients receiving the paravagin*l defect repair (11). Enrollment in this study by Mario Colombo was discontinued after 36 patients owing to the high failure rate of the PVDR for incontinence. Colombo reported the cure as 61% (P , .004) in the PVDR group and 100% (P , .02) 18 of 18 in the Burch group. This failure may be secondary to persistent or recurrent urethrovesical junction descent from relaxation of the anterior vagin*l wall in the midline, despite the restoration of paravagin*l anatomy. The may be evidenced by the fact that in Colombo’s study all of the postoperative Burch patients had a negative urethral angle on cotton swab testing, but only 33% of the PVDR patients. Patients who continued to have midline urethral descent despite paravagin*l support demonstrated high rates of failure. Thus, patient selection in the office by documenting lack of urethral descent during instrumental support of the anterior lateral sulci may be beneficial in increasing the cure rate in PVDR patients. Concomitant PVDR at the time of urethrolysis for the management of voiding dysfunction secondary to urethropexy is a consideration. Webster et al. reported 15 women with voiding dysfunction following cystourethropexy who underwent takedown and substitution with a PVDR (12). All 13 women who had symptoms of bladder instability experienced resolution of their symptoms, and of seven patients who required intermittent self-catheterization preoperatively, only one required catheterization postoperatively. A successful outcome was achieved in 14 of 15 patients. The article underscores the anatomic correction of the PVDR technique, which does not result in elevation of the urethrovesical junction beyond its normal anatomic position. To treat patients receiving a Burch or MMK procedure adequately who have a concomitant paravagin*l defect, a PVDR may be accomplished simultaneously. This is often referred to as a paravagin*l-plus or MMK-plus procedure. In this setting the Burch procedure



would be seen as the primary incontinence operation, and the PVDR corrects a defect and further supports the anterior vagin*l wall. 1. Technique of Outpatient Mini-Incision Paravagin*l Defect Repair Long-acting local anesthetic is infiltrated into the fascia prior to closing the fascia and skin. A 4-cm transverse suprapubic incision is made followed by a 4-cm fascial incision. The fascia is mobilized off the underlying rectus muscle followed by lateral dissection into the space of Retzius. A mini-Bookwalter retractor is placed followed by entry into the bladder dome. The surgeon’s left hand is placed within the vagin* and fiberoptic light facilitates visualization. The surgeon begins on the left side with identification and delineation of the full length of the anterior lateral sulcus. A gauze stick facilitates additional retraction of the bladder, and the anterior lateral sulcus is elevated with the vagin*l hand. Vessels will be noted coursing in a longitudinal course along the sulcus. The obturator foramen is palpated, and care is taken to avoid the nerve and vessels including the aberrant branch of the obturator vein. Sutures are placed initially into the obturator internis when operating on the patient’s left side and in the anterior lateral sulcus when operating on the patient’s right side. A single bite is taken into the obturator internis at the level of the ATFP, and double bites are taken into the vagin*l sulcus. Two to five sutures are placed along the sulcus from an area just inferior to the ischial spine to the symphysis pubis. In elderly patients, the arcuate line may not be visible and the attachment of the vagin* is along a course 1 –1.5 to 2 cm below the obturator foramen. Bites into the obturator internis as 3– 4 mm deep and 1 cm long, avoiding vital structures that are 7.5 mm deep. The ureter courses 2.5 – 3 cm medial to the superior aspect of the anterior lateral sulcus. Delineation of the ureter is possible by use of the vagin*l finger palpating the structure against the abdominal finger. The sutures are tied on the left side of the patient prior to placing sutures on the right. If a concomitant Burch urethropexy is done, the paravagin*l sutures are tied first to establish the proper length of the Burch sutures as they course up to Cooper’s ligament. B.


The MMK procedure was first accomplished in a female on June 8, 1944 (13). Modifications of the MMK must involve suturing of the periurethral tissues to the midline cartilage or periosteum of the symphysis pubis in order to maintain this designation. Mainprize and Drutz in a review of 56 articles through the year 1988 stated that the overall success rate was 86.1% in 2712 cases (13). They noted that even in repeat procedures, the cure rate was high at 84.5%. Lee et al. noted in a series of 549 patients followed 2 – 16 years a 91% subjective cure rate in 227 primary patients and a 90% subjective cure rate in 322 repeat procedures (14). Colombo et al. reported a randomized comparison between the MMK and the Burch procedure (15). A full urodynamic investigation was done 6 months after surgery. The cure rate for the MMK was noted be 65% on urodynamic testing and a subjective cure rate of 85% at mean 3.5 years. The Burch procedure was found to have an objective cure rate of 80%. The MMK is effective in patients with low urethral pressures if they have hypermobility of the urethra. Quadri et al. did a prospective, randomized comparison of the MMK and the Burch urethropexy in patients with low urethral pressures who demonstrated urethral descent (16). Only 15 patients were studied in each group. At 1 year, stress tests were negative in 93% of women who underwent the MMK procedure and 53% of those who underwent the Burch procedure. In their review, Mainprize and Drutz (13) reported the overall complication rate was 21.1% with 5% wound complication rate, a 3.8% urinary tract infection rate, and a 2.5%

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Figure 2 Completed paravagin*l defect repair and Burch urethropexy. The paravagin*l sutures are tied first and determine length of the Burch sutures. The latter are tied without additional tension. This stabilizes, but does not elevate the anterior vagin*. (Used with permission of John Miklos.)

incidence of osteitis pubis. Kammerer reported 15 cases of osteitis pubis diagnosed after 2030 MMK procedures at the Mayo Clinic (17). 1.

Technique of the Outpatient Mini-Incision MMK Procedure

Long-acting local anesthetic is infiltrated into the fascia prior to closing the fascia and skin. A 4-cm transverse suprapubic incision is made followed by a 4-cm fascial incision. The fascia is mobilized off the underlying rectus muscle followed by lateral dissection into the space of Retzius. A mini-Bookwalter retractor is placed followed by entry into the bladder dome. The surgeon’s left hand is placed within the vagin*, and fiberoptic light facilitates visualization. The bladder dome is opened to facilitate precise suture placement. The urethrovesical junction is palpated with one finger in the bladder and two fingers of the vagin*l hand separated by the catheter. The vagin*l hand is positioned with each finger on the urethrovesical junction, and the abdomen hand retracts fat medially, allowing visualization of the white periurethral tissue. Permanent sutures are placed with the needle initially entering closest to the urethra and then coursing lateral in a perpendicular direction for a distance of 1 cm. The sutures are check after placement by palpating with a finger in the bladder to determine distance lateral to the urethra and position relative to the urethrovesical junction. A total of four sutures are placed, two on each side of the urethra with the secondary sutures just distal to the initial urethrovesical junction sutures. All sutures are passed through the midline cartilage of the symphysis taking care to ensure that they are in the inferior aspect of the cartilage, thus avoiding overelevation. The cartilage of the symphysis has less blood supply than surrounding tissues and an aseptic technique is essential. Needles passing through the vagin* should be cut and replaced with a



Figure 3 A small cystotomy allows precise suture placement, ability to check the bladder for suture material and ureteral efflux, and placement of a suprapubic catheter. (Used with permission of the Mayo Foundation.)

clean free-Mayo needle prior to passing through cartilage. The sutures are tied and the bladder is examined to ensure that it is free of suture material and the ureters are examined for efflux. The bladder is then closed in a double layer closure with 2-0 Chromic with incorporation of a 16-gauge catheter into the apex of the incision. The catheter is placed through a right lower quadrant stab incision. C.


In 1961 Burch reported a series 53 retropubic urethropexies (9). In seven of these patients the ATFP served as the area of attachment for the periurethral sutures. In 46 cases the iliopectineal ligament was used. In 1968 Burch reported a 9-year experience with the operation resulting in a 93% cure rate with only 12.5% of the 143 patients having a 5-year follow-up (18). Only 12 patients in the series had undergone a previous incontinence operation. The operative technique was described in detail and included three sutures of 2-0 Chromic attaching the periurethral tissues directly to Cooper’s ligament. Postoperative enterocele occurred in 7.6% of patients despite cul-de-sac reinforcement being added to the procedure early in the series. The majority of Burch procedures performed today are similar to the modification reported by Emil A. Tanagho (19). The article, which did not describe Tanagho’s results, was presented at the Western section meeting of the American Urologic Association in Coronado in 1976. Tanagho placed his sutures in a far-lateral position, used two sutures bilaterally (No. 1 Dexon), and emphasized avoidance of undue tension on the anterior vagin*l wall. He commented that two fingers could be placed between the symphysis and urethra, stressing that the vagin* did not have to be contiguous with Cooper’s ligament.

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Figure 4 The surgeon’s vagin*l hand supports the urethrovesical junction, with one finger on each side of the catheter. Combined intravesical palpation and vagin*l palpation allows precise delineation of the bladder neck and lateral distance of sutures from the urethra. (Used with permission of the Mayo Foundation.)

The concept of not overelevating the vagin*l wall at the time of retropubic urethropexy was an important one and it presaged the hammock hypothesis of John O.L. DeLancey (20). Patients could experience cure with less risk of urinary retention and bladder overactivity secondary to obstruction. It is consistent with the concepts of the hammock hypothesis that Burch procedures should stabilize and not elevate the anterior vagin*l wall. Tanagho’s modification by its lateral placement of sutures, reduced compression, and overelevation of the urethra. It is important when reviewing articles describing Burch results to note the technique utilized and to what degree the anterior vagin*l wall was elevated. Articles that



Figure 5 Sutures are placed 3 – 4 mm lateral to the urethra. A 22-guage catheter is in the urethra. The surgeon’s two fingers straddle the urethra. (Used with permission of the Mayo Foundation.)

describe apposition of the wall to Cooper’s ligament or significant elevation will have a higher incidence of prolonged voiding dysfunction and enterocele formation. There are several studies that document long-term results of the Burch urethropexy. Herbertsson and Iosif studied 72 women who underwent Burch colposuspension with preoperative and postoperative urodynamics (21). Objective follow-up occurred a mean of 9.4 years later. The objective surgical cure rate was 90.3% (a negative stress test with at least 300 cc within the bladder. The enterocele formation rate in this study was 4%. Feyereisl et al. reported urodynamic outcome in 87 patients, 5 – 10 years after Burch urethropexy (3). Patients with greater than grade I prolapse or cystocele were excluded. Inclusion criteria included objective stress leakage in the absence of detrusor instability and documented hypermobility of the urethra. Stress incontinence was objectively cured in 81.6% of patients. Cure was defined as a dry, symptom-free patient, without objective loss during coughing in the standing position with 400 cc of bladder volume. Alcalay et al. reported a 10- to 20-year follow-up of the Burch colposuspension (4). This was a longitudinal retrospective study with a long-term follow-up including symptom review, uroflowmetry, and an extended pad test. Objective cure was defined as inability to demonstrate

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stress incontinence during clinical examination and provocative urodynamics. The authors stated that cure on incontinence is time dependent, with a decline for 10 –12 years when a plateau of 69% is reached. Langer et al. reported a long-term (10 – 15 years) follow-up after Burch colposuspension in 127 patients (5). An additional postoperative urodynamic examination was accomplished at least 10 years after surgery in 109 patients. The cure rate was 93.7%, with cure defined as subjective and objective dryness. Following surgery there was an improvement in symptoms of frequency (P , .001), urgency (P , .01), and urge incontinence (P , .001). 1.

Prospective, Randomized Studies Comparing Burch Urethropexy and Anterior Colporrhaphy Anterior colporrhaphy or the Kelly procedure was utilized in the management of female urinary incontinence for decades. It became popular after the concepts of the paravagin*l defect were lost to common awareness and before creation of other retropubic urethropexies. There remain proponents of the procedure for incontinence correction to date, despite a preponderance of objective evidence supporting retropubic urethropexy for this indication. There are now several prospective, randomized studies comparing Burch urethropexy to anterior colporrhaphy. In 1995 Bergman and Elia reported a 5-year objective follow-up of a surgical comparison between three procedures for the treatment of urinary incontinence (22). The series consisted of 127 patients without a history of previous incontinence surgery. Multichannel urodynamics were performed preoperatively and at 3 months, 12 months, and 5 years postoperatively. Patients were randomized to the anterior colporrhaphy with Kelly plication, Pereyra procedure, and the Burch urethropexy. Ninety-three subjects were available for the 5-year objective follow-up. The success rates were 37% for the anterior colporrhaphy, 43% for the Pereyra procedure, and 82% for the Burch urethropexy. Seventy percent of the colporrhaphy patients had a urethrovesical junction descent at 5 years, compared with 7% of the Burch patients. Many patients who had cure at 1 year but demonstrated a positive cotton swab test, were noted to be failures at 5 years. Kammerer-Doak performed a randomized trial comparing the Burch urethropexy to the modified anterior colporrhaphy (23). Thirty-five patients were randomized with preoperative and postoperative urodynamic testing as a component of the study. Objective cures 1 year after surgery showed 16 of 18 (89%) of Burch patients were cured compared to five of 16 (31%) of colporrhaphy patients. Subjective and objective ratings of incontinence severity by questionnaires and pad testing were significantly lower for the Burch patients than for the colporrhaphy patients. Mobility of the urethrovesical junction was lower for the Burch patients. Liapis et al. reported a randomized study of three operations for stress incontinence, the MMK, Burch, and anterior colporrhaphy (24). The patients were examined clinically and urodynamically preoperatively and 60 months after surgery. There was a significant difference in results between the procedures at 5 years. The cure rate was 89% for the Burch procedure and 56% and 67% for the AC and MMK, respectively (P , .001). 2.

Technique of Mini-Incision Outpatient Modification of the Burch Urethropexy Long-acting local anesthetic is infiltrated into the fascia prior to closing the fascia and skin. A 4-cm transverse suprapubic incision is made followed by a 4-cm fascial incision. The fascia is mobilized off the underlying rectus muscle in the usual fashion followed by lateral dissection into the space of Retzius. A mini-Bookwalter retractor is placed followed by entry into the



bladder dome. A suture tag is placed at the superior aspect of the bladder incision. The surgeon’s left hand is placed within the vagin*, and fiberoptic light facilitates visualization. Two sutures of No. 1 Ethibond are placed on each side of the urethra, taking double bites with each suture through almost full-thickness vagin*. The initial suture is at the urethrovesical junction, and the second suture is 1 cm inferiorly. All sutures are at least 4 mm lateral to the urethra. Precise placement of each suture is confirmed by subsequent palpation via the cystotomy. The lateral distance from the urethra, the position relative to the urethrovesical junction, the affect on the urethra with suture elevation, and the distance of the lower suture from the urethral meatus are noted. The retractor is removed from each side during placement of sutures through Cooper’s ligament. The rectus muscle on the side of placement is retracted with Greene retractors. Each strand of the suture pairs is placed through the ligament, with the second strand of each pair taking a second bite into the ligament. Needles, which have passed through the vagin*, are removed and replaced with free-Mayo needles prior to passage through Cooper’s ligament. The interior of the bladder is then examined for absence of suture material and bilateral efflux of urine via the ureters. The Foley catheter is removed and a cotton swab test is performed with the table and patient’s back parallel to the floor. A zero to 2108 angle to the horizontal is established by elevating or loosening the sutures. The goal of the procedure is stabilization rather then elevation. The sutures are then tied with precise square knots, maintaining equal and opposite tension on the strands while tying. The bladder is then closed in a double layer closure with 2-0 Chromic with incorporation of a 16-gauge catheter into the apex of the incision. The catheter is placed through a right lower quadrant stab incision.

Figure 6 The Marshall-Marchetti-Krantz sutures are placed into the vagin* and cartilage of the symphysis. After placing a double bite into the vagin*, the needle is removed and replaced with a new freeMayo needle prior to placement into the cartilage. This decreases risk of infection. A total of four sutures are placed. (Used with permission of the Mayo Foundation.)

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Figure 7 The bladder is closed in a double-layer closure incorporating the catheter into the incision. (Used with permission of the Mayo Foundation.)



Patients with genuine stress urinary incontinence and hypermobility of the urethra in the absence of severe bladder overactivity are candidates for Burch urethropexy. This includes patients with low urethral closure pressures or low Valsalva leak-point pressures if they also demonstrate urethral hypermobility. The best definition of intrinsic sphincteric deficiency is functional: stress urinary incontinence despite complete support of the urethra in the absence of uninhibited bladder contractions. These patients are not candidates for urethropexy because they lack urethral mobility. Bergman et al. performed a study showing that patients who have ,308 of urethral descent with urinary stress incontinence have a 55% failure rate associated with Burch urethropexy (25). Data on the transvagin*l tape (TVT) procedure show that individuals with a nonmobile urethra and stress incontinence are also at increased risk of failure with TVT surgery (2). Patients with low urethral pressures who have urethral junction rotation are not at increased risk of failure following Burch urethropexy. Sand et al. performed a prospective randomized comparison of the pubovagin*l sling procedure and the Burch urethropexy in patients with low urethral pressures (26). The cure rate was comparable in the two procedures. Hsieh et al. confirmed this in a separate study (27). The aim of their study was to determine whether an isolated low Valsalva leak-point pressure could be an independent risk factor for Burch failure in patients with a normal maximum urethral closure pressure. Twenty-four women with objectively proven stress incontinence, Valsalva leak-point pressures ,60 cmH2O and



MUCP values .20 cmH2O were evaluated preoperatively and postoperatively. At .1-year follow-up, 22 of the 24 (91.7%) patients were objectively continent. Patients with preoperative hypermobility of the urethra who demonstrate stress incontinence postoperatively, despite restoration of urethral support, have intrinsic sphincteric deficiency. This may occur after any operation for stress incontinence, including on occasion the pubovagin*l sling procedure. This failure must be secondary to occult deficiency in nerve, muscle, and connective tissue that could not be diagnosed preoperatively. This occult deficiency results in deficient urethral resistance despite restored urethral support after surgery. We have no urodynamic parameters that predict which preoperative patients will fall into this group. The future may hold promise in diagnosing this tendency through laboratory assessment of deficient muscle, nerve, and connective tissue. As an example of such assessment, Kenton et al. reported on the role of urethral electromyography in predicting patients who have preoperative urethral hypermobility, but fail to have their stress leakage repaired with Burch urethropexy (28). Eighty-nine women who underwent preoperative testing with urethral EMG and cystometrograms were also assessed postoperatively. Fifty-nine of 74 women (80%) were objectively cured, and 15 women had persistent urinary stress incontinence at 3 months. Women who were cured did not differ from those who failed in age, parity, menopausal status, maximum urethral closure pressure, Valsalva leak-point pressure, maximum cystometric capacity, and detrusor instability or prolapse stage. Electrical activity of the urethra was calculated in these patients during rest, voluntary urethral squeezing, repetitive coughing, and bladder filling. There was no difference in any EMG parameters between the two groups when measured at rest, with urethral squeezing, or during bladder filling. Women who were cured did demonstrate better motor unit action potential activation with repetitive coughing than those with persistent leakage.



Vancaille and Schuessler reported the first laparoscopic colposuspension (MMK) case series in 1991 (29). The literature reflects a lack of standardization and precise outcome measurements. Prospective, randomized comparisons of laparoscopic to open technique include the studies by Summitt et al. and Fatthy et al. (30,31). Comparable rates of stress incontinence cure were noted between the two groups in each of the studies. Prospective, randomized studies that show increased cure by open technique include Burton et al. (32) and Su et al. (33). Su examined success at 1 year and showed an 84% cure with the laparoscopic approach and a 95.6% cure with the open technique. The randomized study by Burton included a 3-year follow-up with a 40% failure rate in the laparoscopic group compared with a 15% failure rate in the open group. Several authors have reported an increased complication rate with the laparoscopic approach. Speights et al. reported on frequency of lower urinary tract injury at laparoscopic Burch and PVDR (34). There were no ureteral injuries, and four patients of 171 had cystotomies. Walter et al. compared morbidity and costs of laparoscopic versus open Burch when performed with concomitant vagin*l prolapse repairs (35). A retrospective review of 76 laparoscopic and 143 open Burch procedures with at least one concomitant vagin*l repair for symptomatic prolapse was accomplished. The group with open urethropexy had an older age, greater degree of prolapse, fewer concurrent hysterectomies, and a greater number of vagin*l procedures than the group with the laparoscopic Burch procedures. There were minimal differences in complications. There were no differences in estimated blood loss, operative time, hemoglobin change, hospitalization, or hospital charges between the two groups. Considering that a significant percentage of incontinent patients require some type of concomitant prolapse

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repair, the benefits of laparoscopy in this setting is less evident. Kholi et al. showed that despite shorter hospital stay, the direct costs of laparoscopic Burch were higher than those of the open technique (36). Persson et al. showed the benefit of two sutures on each side of the urethra in comparison to one (37). Objective cure rate was 83% in the women with two sutures, compared to the 58% of patients with one suture. The current literature would indicate additional large prospective, randomized studies with adequate power are needed.



Symptoms of voiding dysfunction and de novo detrusor instability are most likely increased by excessive elevation of the vagin* and secondarily the bladder trigone at urethropexy. Greater elevation may result in obstruction and secondary effects on bladder muscle. The benefit of stabilization and not elevation may be an important factor to consider in decreasing postoperative complications of voiding dysfunction. Alcalay et al. noted that the most frequent complication in their series was de novo detrusor instability (DI) (14.7%) (4). The rate of de novo DI was commensurate between those having primary or secondary operations. The authors noted that the development of de novo DI is a bad prognostic factor for long-term objective cure. Women who developed postoperative DI continued to have symptoms of urgency and urgency incontinence for .10 years. In addition, Alcalay et al. noted that 22% of patients still complained of voiding dysfunction 10 years or more after surgery, and four of these patients underwent urethrotomy. The authors found that preoperative factors had poor predictive value for postoperative voiding dysfunction. In an earlier study, Stanton’s group had followed 92 patients with no evidence of preoperative DI on urodynamics who had undergone Burch urethropexy. Postoperative urodynamics showed that 75 (81.5%) had stable bladders and 17 (18.5%) had unstable bladders (38). In Langer et al.’s 10-year follow-up objective study, the incidence of de novo DI was 16.6% and 18.7% of postoperative patients developed anatomical defects (5). De novo DI appeared in 12 of 17 patients during the first year of follow-up. It took longer for the majority of anatomical defects to become manifest. In the study by Feyereisl et al., the prevalence of postoperative DI was noted to be 14.9% and the prevalence of late voiding difficulties was 4.6% (3). In the study by Kammerer et al., the complication rate was no different in the Burch group compared to the anterior colporrhaphy group (23). De novo DI complicated the postoperative course in two of 40 (5%) patients in the prospective study of Colombo et al. (this was half the amount noted in the MMK group) (11). Vierhout et al. reviewed six studies totaling 396 patients who had undergone urethropexy. Sixty-eight (17%) developed de novo DI (39). The prevalence varied from 5% to 27% in the different studies. Current knowledge indicates that patients with mixed incontinence who demonstrate DI at low bladder volumes are at higher risk of failure from retropubic urethropexy. This does not mean that patients with detrusor instability demonstrated at higher volumes are not candidates for urethropexy. The majority of female incontinent patients over the age of 60 probably have mixed incontinence. Colombo, in a retrospective study, showed that in a group of mixed-incontinence patients, the objective stress incontinence cure rate 2 years after urethropexy was 75% (40). To be considered cured, patients had to be subjectively free of any incontinence symptoms.



Figure 8 The completed Marshall-Marchetti-Krantz procedure. The sutures are in the lower one-half of the symphysis avoiding excessive elevation. (Used with permission of the Mayo Foundation.)

The incidence of long-term urinary retention and its adverse sequelae after urethropexy is more difficult to estimate. The studies have not reported specific residual urine amounts at 5– 10 years of follow-up. It is unclear in Alcalay et al.’s study how many patients had persistently high residual urine values in the group of voiding dysfunction patients (4). Four of 366 patients had subsequent urethrotomy. Residual urine values were not reported in the 10- to 20-year follow-up category. Feyereisl et al. in their 5- to 10-year follow-up of Burch urethropexy patients noted a residual urine value .60 mL in 16% of patients (3). The number of patients demonstrating longterm residual urine determinations .150 mL or 200 mL is not reported. The risk of enterocele or rectocele formation after colposuspension may also be decreased by avoidance of excessive elevation of the vagin*. Some series show up to a 26.7% risk of prolapse following colposuspension (41). Demirci and Petri have documented a review of perioperative complications in the Burch literature (42). Wiskind et al. reported a need for blood transfusion in 0.7– 2.3% of cases (41).

Retropubic Urethropexy


Figure 9 The Burch sutures are placed with each strand of the suture pair going through Cooper’s ligament. Stabilization and not elevation of the anterior wall is achieved in order to decrease the risks of voiding dysfunction and bladder overactivity. (Used with permission of John Miklos. Copyright John Miklos.)



Objective studies of hysterectomy at the time of urethropexy show no effect on incontinence cure or longevity of cure. Meltomaa et al. in a recent prospective study looked at morbidity and long-term subjective outcome between Burch colposuspension alone and Burch with concomitant abdominal hysterectomy (43). There was no difference in subjective short- and long-term (5 years) outcome. Complications related to operation occurred in 29.2% of the Burch group and 46.2% of the Burch/hysterectomy group. Complications were mainly related to infection and postoperative anemia. The reoperation rate was 1.5% for the Burch group and 2.6% for the Burch/hysterectomy group. Sze et al. compared the surgical morbidity, postoperative course, and hospital charges of Burch colposuspension performed in conjunction with abdominal versus vagin*l hysterectomy (44). The abdominal route had significantly longer hospital stays and higher hospital charges than the vagin*l group.



The retropubic urethropexy remains an important procedure in the surgical management of female urinary incontinence. Burch urethropexy has a replete literature with some of the longest objective follow-up series of any incontinence procedure. It is effective in patients with low



urethral pressure who have hypermobility of the urethra. It can be accomplished with a miniincision allowing precise placement of sutures, and allows performance of a concomitant PVDR with site-specific correction of paravagin*l defects. REFERENCES 1. 2.

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12. 13. 14. 15.



18. 19. 20.

Ulmsten U, Henriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local anesthesia for treatment of female urinary incontinence. Int Urogynecol J 1996; 7:81– 86. Nilsson CG, Kuuva N, Falconer C, Rezapour M, Ulmsten U. Long-term results of the tension-free vagin*l tape (TVT) procedure for surgical treatment of female stress urinary incontinence. Int Urogynecol J 2001; Suppl. 2:S5– S14. Feyereisl J, Dreher E, Haenggi W, Zikmund J, Schneider H. Long-term results after Burch colposuspension. Am J Obstet Gynecol 1994; 171:647 – 652. Alcalay M, Monga A, Stanton SL. Burch colposuspension: a 10 – 20 year follow up. Br J Obstet Gynaecol 1995; 102:740 – 745. Langer R, Lipsh*tz Y, Halperin R, Pansky M, Bukovsky I, Sherman D. Long-term (10– 15 years) follow-up after Burch colpsuspension for urinary stress incontinence. Int Urogynecol J 2001; 12:323– 327. White GR. A radical cure by suturing lateral sulci of vagin* to white line of pelvic fascia. JAMA 1909; 21:1707 –1708. White GR. An anatomical operation for the cure of cystocele. Am J Dis Wom Child 1912; 65:286– 290. Marshall VF, Marchetti AA, Krantz KE. The correction of stress incontinence by simple urethrovesical suspension. Surg Gynecol Obstet 1949; 88:509. Burch JC. Urethrovesical fixation to Cooper’s ligament for correction of stress incontinence, cystocele, and prolapse. Am J Obstet Gynecol 1961; 81:281. Richardson CA, Lyon JB, Williams NL. A new look at pelvic relaxation. Am J Obstet Gynecol 1976; 126:568– 571. Colombo M, Milani R, Vitobello D, Maggioni A. A randomized comparison of Burch colposuspension and abdominal paravagin*l defect repair for female stress urinary incontinence. Am J Obstet Gynecol 1996; 175:78 – 84. Webster GD, Kreder KJ. Voiding dysfunction following cystourethropexy. J Urol 1990; 144:670– 673. Mainprize TC, Drutz HP. The Marshall-Marchetti-Krantz procedure: a critical review. Obstet Gynecol Surv 1988; 43:724 –729. Lee RA, Symmonds RE, Goldstein RA. Surgical complications and results of modified MarshallMarchetti-Krantz procedure for urinary incontinence. Am J Obstet Gynecol 1979; 53:447– 450. Colombo Colombo M, Scalambrino S, Maggioni A, Miliani R. Burch colposuspension versus modified Marshall-Marchetti-Krantz urethropexy for primary genuine stress urinary incontinence: a prospective, randomized trial. Am J Obstet Gynecol 1994; 171:1573 – 1579. Quadri G, Magatti F, Belloni C, Barisani D, Nicola N. Marshall-Marchetti-Krantz urethropexy and Burch colposuspension for stress urinary incontinence in women with low pressure and hypermobility of the urethra: early results of a prospective randomized clinical trial. Am J Obstet Gynecol 1999; 181:12– 18. Kammerer-Doak DN, Cornella JL, Magrina JF, Stanhope CR, Smilack J. Osteitis pubis after Marshall-Marchetti-Krantz urethropexy: a pubic osteomyelitis. Am J Obstet Gynecol 1998; 179:586– 590. Burch JC. Cooper’s ligament urethrovesical suspension for stress urinary incontinence. Am J Obstet Gynaecol 1968; 6:764 – 774. Tanagho EA. Colpocystourethropexy: the way we do it. J Urol 1976; 116:751– 753. DeLancey JOL. Structural support of the urethra as it relates to stress urinary incontinence: the hammock hypothesis. Am J Obstet Gynecol 1994; 170:1713– 1720.

Retropubic Urethropexy 21. 22. 23. 24. 25. 26.

27. 28. 29. 30. 31. 32. 33. 34. 35.

36. 37.

38. 39. 40. 41. 42. 43.



Herbertsson G, Iosif GS. Surgical results and urodynamic studies ten years after retropubic urethropexy. Acta Obstet Gynaecol Scand 1993; 72:299– 301. Bergman A, Elia G. Three surgical procedures for genuine stress incontinence: five-year follow-up of a prospective randomized study. Am J Obstet Gynecol 1995; 173:66– 71. Kammerer-Doak DN, Dorin MH, Rogers RG, Cousin MO. A randomized trial of Burch urethropexy and anterior colporrhaphy for stress urinary incontinence. Obstet Gynecol 1999; 93:75 – 78. Liapis AE, Asimiadis V, Loghis CD, Pyrogiotis E, Zourlas PA. A randomized prospective study of three operative methods for genuine stress incontinence. J Gynecol Surg 1996; 12:7– 13. Bergman A, Koonings PP, Ballard CA. Negative Q-tip test as a risk factor for failed incontinence surgery in women. J Reprod Med 1989; 34:193 – 197. Sand PK, Winkler H, Blackhurst DW, Culligan PK. A prospective randomized study comparing modified Burch retropubic urethropexy and suburethral sling for treatment of genuine stress incontinence with low-pressure urethra. Am J Obstet Gynecol 2000; 182:30 –34. Hsieh GC, Klutke JJ, Kobak WH. Low Valsalva-leak point pressure and success of retropubic urethropexy. Int Urogynecol J 2001; 12:46 – 50. Kenton K, Fitzgerald MP, Shott S, Brubaker L. Role of urethral electromyography in predicting outcome of Burch retropubic urethropexy. Am J Obstet Gynecol 2001; 185:51 –55. Vancaille TG, Schuessler W. Laparoscopic bladderneck suspension. J Laparoendosc Surg 1991; 1:169– 173. Summitt RL, Lucente V, Karram MM. Randomized comparison of laparoscopic and transabdominal Burch urethropexy for the treatment of genuine stress incontinence. Obstet Gynecol 2000; 95(Suppl):2. Fatthy H, El Hoa M, Samaha I, Abdallah K. Modified Burch colposuspension: laparoscopy versus laparotomy. J Am Assoc Gynecol Laparosc 2001; 8:99 – 106. Burton G. A three year randomized urodynamic study comparing open and laparoscopic colposuspension. Neurourol Urodyn 1993; 16:353 –354. Su TH, Wang KG, Hsu CY. Prospective comparison of laparoscopic and traditional colposuspension in the treatment of genuine stress incontinence. Acta Obstet Gynecol 1997; 76:576 – 582. Speight SE, Moore RD, Miklos JR. Frequency of lower urinary tract injury at laparoscopic Burch and paravagin*l repair. J Am Assoc Gynecol Laparosc 2000; 7:515 – 518. Walter AJ, Morse AN, Hammer RH, Hentz JG, Magrina JF, Cornella JL, Magtibay PM. Laparoscopic versus open Burch retropubic urethropexy: comparison of morbidity and costs when performed with concurrent vagin*l prolapse repairs. Am J Obstet Gynecol 2002; 186:723 – 728. Kholi N, Jacobs PA, Sze EHM, Roat TW, Karram MM. Open compared with laparoscopic approach to Burch colposuspension: a cost analysis. Obstet Gynecol 1997; 90:411 – 415. Persson J, Wolner-Hanssen, P. Laparoscopic Burch colposuspension for stress urinary incontinence: a randomized comparison of one to two sutures on each side of the urethra. Obstet Gynecol 2000; 95:151– 155. Cardozo LD, Stanton SL, Williams JE. Detrusor instability following surgery for genuine stress urinary incontinence. Br J Urol 1979; 51:204– 207. Vierhout ME, Mulder AFP. De novo detrusor instability after Burch colposuspension. Acta Obstet Gynaecol Scand 1992; 71:414– 416. Colombo M, Zanetta G, Vitobello D, Milani R. The Burch colposuspension for women with and without detrusor overactivity. Br J Obstet Gynaecol 1996; 103:255 – 260. Wiskind AK, Creighton SM, Stanton SL. The incidence of genital prolapse after the Burch colposuspension. Am J Obstet Gynecol 1992; 167:399 – 405. Demirci F, Pertri E. Perioperative complications of Burch colposuspension. Int Urogynecol J 2000; 11:170– 175. Meltomaa SS, Haarala MA, Taalikka MO, Kiiholma PJA, Alanen A, Makinen JI. Outcome of Burch retropubic urethropexy and the effect of concomitant abdominal hysterectomy: a prospective longterm follow-up study. Int Urogynecol J 2001; 12:3– 8. Sze EHM, Kohli N, Miklos JR, Roat TW, Karram MM. Comparative morbidity and charges associated with route of hysterectomy and concomitant Burch colposuspension. Obstet Gynecol 1997; 90:42– 45.

19 Laparoscopic Treatment of Urinary Stress Incontinence Thomas L. Lyons Center for Women’s Care and Reproductive Surgery, Atlanta, Georgia, U.S.A.



The treatment of urinary incontinence is a costly endeavor in the United States with over billion dollars spent each year when all forms of management are considered, including the sale of adult diapers and the cost of medical and surgical care. Incontinence remains the most common cause for tertiary admission for long-term custodial care in the older patient. Since urinary stress incontinence (USI) is the most common type of incontinence and the numbers of this diagnosis are increasing owing to the active postreproductive years population, the incidence of this already common disorder is becoming more frequent. Stress incontinence occurs almost exclusively in women and is stated to occur, at least to some degree, in 85% of women over the age of 18. The majority of women with USI are multiparous, and pregnancy or parturition, with its accompanying hormonal effects, pelvic floor, and pelvic neurological damage, is at the basis for the problem. In a majority of cases, patients are able to manage their symptoms using one or a combination of medical therapies, behavior modification, and pelvic floor conditioning. These therapies include Kegel exercises, behavior modification, electrical or ultrasonic stimulation of pelvic musculature, and a number of pharmacologic agents that act in a neuroleptic manner to improve urethral sphincter tone. However, if these alternatives have been exhausted, then surgery is the appropriate solution. The goal of surgery in this and every instance is to provide an effective solution with minimal medical and economic morbidity. Because of the pandemic nature of USI and the difficulty of reliably correcting the problem with existing surgical techniques, over 300 surgical procedures have been developed over the years to deal with the problem (1 –11). Similarly, as minimally invasive techniques have been applied in this area, a multitude of variations and new procedures have been proposed, many of which have “borrowed” names from traditional procedures whether the laparoscopic procedure resembled the old procedure or not. This means that some “laparoscopic Burch” procedures are not Burch procedures in the real sense of the word. The purpose of this chapter is to present some of the variations which have been proposed and what available data are present on these modifications. In addition, we will attempt to carefully describe the procedure that we currently perform and present the data and rationale that supports this approach. Most gynecologists will agree that the gold standard surgically speaking in the treatment of USI is retropubic culposuspension (Burch procedure) (2,3). The Marshall, Marchetti, Krantz 309



(MMK) procedure is also included in this discussion (1). We also include the paravagin*l repair, which was described by Richardson in the mid-1970s, as a component of this type of repair that is referred to as “site-specific defect repair of the pelvic floor” (4). The other type of surgical treatment recommended for USI is the suburethral sling procedure (11). This is the preferred method by most urologists, and although we have performed these procedures with laparoscopic assistance, we do not suggest that this should be the norm. It is important to apply a global approach to pelvic floor reconstruction, as rarely do the defects described here exist in absence of corresponding defects of the posterior compartment. Therefore, when the treatment of USI is considered, all defects are approached and treated at the same time. This invariably improves outcomes not only in the short term, but also extended follow-up is improved.



Originally, vagin*l approaches to this USI problem were considered the only alternative to pessaries and nonsurgical methods of improving continence. In fact, the problem was rarely discussed and the initial descriptions of anterior colporraphy with the Kelley Kennedy plication in 1913 were rapidly accepted over the existing techniques, which had greater morbidity with uniformly poor outcomes (5). The subsequent development of vagin*l approaches progressed under the auspices of proficient surgeons such as Nichols and Richardson into the latter half of the 20th century (4,6). Still, however, there were treatment failures particularly, over long-term follow-up. Midcentury, a retropubic approach to the problem was suggested by Marshall, Marchetti, and Krantz (MMK) (1). This retropubic urethropexy seemed to improve outcomes but also brought new morbidity of osteitis pubis and urinary retention. A decade later the Burch modification was proposed and later modified by Tanangho and others into the procedure that is currently being used by most gynecologists and urologists (12). The clinical success rates quoted short term are in the high 80% range for this procedure. Despite the excellent clinical outcomes, there was concern regarding the morbidity associated with the need for laparotomy to perform these procedures which gave rise to a number of new procedures. One group of these procedures were called the “needle procedures.” Most notable among these proposed procedures were those described by Raz (7), Pereyra (8), Stamey (9), and Gittes (10). In further investigations these procedures have yielded relatively disappointing success rates of 50– 70% (13). The sling procedures which were first applied in the 1970s have produced good clinical outcomes, particularly in those patients with intrinsic sphincter deficiency (ISD) and mixed incontinence (11). These procedures also have morbidities that include the need for laparotomy in some cases and the potential for rejection/infection of the sling material itself. Although many of these problems have been obviated, very few gynecologists perform sling procedures routinely, and most urologists who use them do not approach the posterior and/or concomitant anterior compartment defects. The late 1980s and the 1990s brought the replacement of a number of laparotomy-based gynecologic procedures with laparoscopic alternatives. In most instances, the laparoscopic approaches have produced similar clinical results with significant reductions in overall costs and morbidity. Logically, applications of minimally invasive techniques to USI and defects of the anterior compartment were the next step in this area. A Medline search of information on this application in 2002 reveals a wealth of papers on the laparoscopic applications to USI. However, standardization of these papers is difficult to assess but will be presented in the next segment of this discussion.

Laparoscopic Treatment of USI


The first report of laparoscopic retropubic treatment of USI was by Vancaille and Shuessler, a gynecologist and an urologist, respectively, in 1991 (14). Vancaille has subsequently developed his techniques after Zacharin, the well-known Australian surgeon (15), while other gynecologists in the United States, including Lui, Lyons, and others, have pursued a site-specific approach to retropubic repairs (16 – 19). Table 1 summarizes the results of a Medline search on laparoscopic applications to USI.



The technique that will be described here is the favored technique in our institution and this technique is similar to that of Lui, Miklos, and Wattiez. There are differences, but those Table 1 comesa

Laparoscopic Urinary Stress Incontinence Procedures—Clinical Out-

Reference Vancaillie et al. (14) Liu et al. (18) Liu (19) Burton (20) Gunn et al. (21) Liu (22) Nezhat (23) Lam et al. (24) Langebrekke et al. (25) Lyons et al. (26) Lyons (27) Polascik et al. (28) Von Theobald et al. (29) Cooper et al. (30) Kung et al. (31) Nieves (32) Radomski (33) Shwayder (34) Burton (35) Lobel et al. (36) Papasakelariou et al. (37) Su et al. (38) Das (39) Lee et al. (40) Miannay et al. (41) Ross (42) Saidi et al. (43) Fatthy et al. (44) Lee et al. (45) Zullo et al. (46) a

Patients (n)

Follow-up (months)

Cure rate (%)

9 107 58 30 15 132 62 15 8 20 38 12 37 113 31 35 34 20 30 35 32 46 10 48 36 48 70 34 150 30

3 3 – 27 24 12 4–9 24 8 – 30 9 3 12 18 21 – 36 42 1 – 28 14 – 30 4 – 30 12 – 26 12 – 54 36 1 – 51 24 12 36 26 17 30 – 41 5 – 27 18 36 12

100 97.2 94.8 73 100 96.2 91.9 98 88 92 90 83 86 87 97 90 85 100 60 68.6 90.6 80.4 90 93.8 79 89 91.4 87.9 90.7 89

Patient reports no loss of urine with Valsalva.



differences are predominately typical surgeon-specific idiosyncrasies. After an accurate diagnosis is made, the patient is prepped for surgery with a magnesium citrate bowel prep and is consented for pelvic floor reconstruction. If there are indications for hysterectomy, then hysterectomy is performed with laparoscopic supracervical hysterectomy (LSH), the preferred procedure. This allows excellent ability to reconstruct the pericervical ring of fascia and also facilitates the repair of the posterior compartment and vault support. The patient is positioned as shown in Figure 1. Dual monitors placed at the patient’s feet are at or above eye levels for surgeon comfort. The trocar placement is as shown in Figure 2. The midline trocars are 10/12 mm in diameter and allow for passage of the laparoscope in the subumbilical site and the introduction and extraction of curved needles of adequate size through the suprapubic site. The lateral trocars are 5 mm in diameter and are placed well lateral to the rectus muscles and as high as the suprapubic midline trocar at least four fingerbreadths above the symphysis. This allows an adequate angle to access both the space of Retzius and the posterior cul-de-sac. A 20-cc bulb Foley catheter is placed in the bladder. After completion of the hysterectomy, posterior compartment repair is accomplished which usually includes a high McCall’s culdoplasty and vault suspension. This is performed with #0 Ethibond (Ethicon Inc., New Brunswick, NJ) suture in an ipsilateral fashion. A relaxing incision is made medial to the ureter on each side to identify and avoid kinking of the ureter with this suspension procedure. The space of Retzius is entered by making an incision in the anterior wall peritoneum 1 inch above the symphysis pubis. This incision is extended bilaterally to the obliterated umbilical ligaments. Blunt and sharp dissection is used to identify first the symphysis and Cooper’s ligaments and then the lateral pelvic sidewall, obturator neurovascular canal, neurovascular bundle, the ischial spine, the arcus tendinius (White’s line of the pelvis), the arcus of the levator ani, and the paravagin*l fascia (Fig. 3). The entire area is cleared or fat and areolar

Figure 1

Laparoscopic Treatment of USI


Figure 2

tissue (Tanangho modification) (12). Then the endopelvic fascia of the vagin* is then sutured using #2-0 Ethibond (Ethicon Inc., New Brunswick, NJ) to the corresponding arcus tendinius fascia pelvis, thus correcting the lateral cystocele defect. This suture can be placed as an interrupted suture or in a running fashion. After both paravagin*l defects have been repaired in

Figure 3



Table 2 Follow-up Laparoscopic Burch Urethropexya Suture Vicryl Ethibond

Success % (N)

Failure % (N)

50% (14) 76% (60)

50% (14) 24% (19)


Based on 80.7% response rate.

this fashion then the Burch sutures are placed. Ethibond #0 suture is placed in an interrupted figure of eight fashion through the endopelvic fascia 1 – 2 cm lateral to the urethra with one suture at the midurethral level and one at the urethrovesical junction. These sutures are then taken through Cooper’s ligament and tied, stabilizing the urethra and the U/V junction. This repair corresponds to the paravagin*l-plus repair described by Shull in the late 1980s and constitutes completion of the repair of the anterior compartment. The anterior peritoneal defect is closed using #2-0 Vicryl (Ethicon Inc., New Brunswick, NJ) in a running purse-string manner. Cystoscopy is performed 5 min after 5 cc of indigo carmine is injected intravenously documenting ureteral patency and the absence of suture material in the bladder. A 17 or 19 Fr cystoscope with 708 lens is helpful in this portion of the procedure. Absence of ureteral effluent requires investigation of ureteral patency. The catheter is removed as soon as the patient is ambulatory and the patient is allowed to void. Voiding abnormalities are common in the first few days but resolve rapidly. In the patient who is unable to void 5 h after the catheter is removed, the catheter is replaced and left overnight. Virtually all patients are able to void by morning. However, all patients are counseled about voiding difficulties postprocedure and are taught selfcatheterization for this instance. Patients are discharged from the facility when discharge criteria are met and they wish to leave. This means that all patients are discharged within 23 h, and the average discharge is accomplished in 11 h. Patients are encouraged to resume most normal activity as soon as they feel comfortable but are restricted from intercourse and repetitive straining or heavy lifting for 4 – 6 weeks. It is important to note at this time in the technical segment of this chapter that the use of permanent suture material is significant when treating support type defects. The present author’s experience confirms this need. Table 2 summarizes the early experience in laparoscopic Burch procedures when first absorbable, and then permanent materials were used. Success rates have been maintained since that time when using permanent suture material. Other described techniques involve the use of Prolene or other mesh materials and stapling or tacking devices to attach the mesh to Cooper’s ligament and the paravagin*l fascia, respectively (47), the use of the laparoscope to facilitate the performance of a “needle” or a sling procedure (36), and the placement of sclerotic materials into the space of Retzius under laparoscopic guidance all being described as a laparoscopic Burch procedure. Representative data from these techniques are included in Table 1. Conclusions regarding the efficacy of these procedures are left to the reader.



Ultimately, there are a number of factors that will eventually contribute to the adoption of laparoscopically directed pelvic floor reconstruction. These are the same factors that should

Laparoscopic Treatment of USI


govern the adoption of any surgical or medical procedure. First and foremost, the procedure must accomplish the task that it is proposed to do. There seems to be ample evidence that this goal can be achieved with laparoscopic retropubic culposuspension. In the data generated to date, although little level I evidence is available, it appears that in competent hands results should be equivalent at worst. Secondly, morbidity should be improved or no worse than existing techniques. Again, the evidence appears convincing that laparoscopic procedures definitely reduce short-term morbidity and mortality when compared to laparotomy procedures. There are some who argue that laparoscopy has a morbidity in and of itself, but the arguments for this position thus far have remained unconvincing. Medicolegally speaking, entry into the abdomen has a definable morbidity whether that entry is made laparoscopically or via laparotomy. Thirdly, there is the question of cost. There certainly is no question that cost is and should be an issue in the performance of surgery. We must look, therefore, at cost and not at “charges,” which some would have us believe are the actual costs of surgery. Charges are what the hospital or facility charges the patient or the patient’s insurer for the procedure and almost always bear only a vague resemblance to the actual cost of the procedure. Operating-room time is an issue, and, early in the learning curve, any new procedure will take more time, but it is our observation that this is no longer an issue once proficiency is gained. No special materials or devices are needed for this procedure, although some have been suggested. Intangible costs of more rapid return to work have not been addressed in the literature to date but based on information derived from work done with laparoscopic cholecystectomy and laparoscopic hysterectomy the cost savings from these procedures could be substantial (48,49). Finally, there is the question of technical training and credentialing. The procedures described are not new procedures as such but only different modes of access to perform “triedand-true” procedures. Certainly, suturing laparoscopically is one of the more difficult skills to learn by the novice laparoscopist, but it does not represent a barrier that is in any way unreachable by a surgeon who is willing to practice this technique and apply it in his or her practice. The potential reduction in morbidity for that surgeon’s patients is well worth the extra efforts involved. There have also been concerns that somehow adoption of these procedures would signal an end to vagin*l surgery and its attendant discipline. It is this author’s belief that the further anatomic knowledge that is attainable with laparoscopic surgery can serve to improve the vagin*l skills of the operator and potentially open more vagin*l opportunities for possible success in correcting these defects. Pelvic floor reconstruction is a discipline that, in reality, has only one century of history. In that period of time, great strides have been made and many solutions have been found to these problems that affect women in their day-to-day lives. At the same time, advances have been made in surgery that have made surgical procedures safer and more effective for our patients. At the end of the 20th century, operative laparoscopy entered the scene and has made an impact on numerous gynecologic and general surgical procedures (50). Owing to the technical difficulty of some of these procedures, assimilation into the mainstream of therapeutic options has been less rapid (51). Lack of level I evidence has been suggested as the reason for this slow uptake, but since there is a dearth of such evidence for existing procedures, it is doubtful that this is the case. How best to perform pelvic floor reconstruction, and what are the anatomic and what are the physiologic explanations for these disorders and their attendant symptomologies are questions for which answers remain lacking. This is truly a surgical field that is a “work in progress.” It is felt that if laparoscopically directed approaches can further any of this knowledge, anatomically or surgically, then the effort was well spent.



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42. 43. 44. 45. 46.

47. 48. 49. 50. 51.


Polascik TJ, Moore RG, Rosenberg MT, Kavoussi LR. Comparison of laparoscopic and open retropubic urethropexy for treatment of stress urinary incontinence. Urology 1995; 45:647 – 652. Von Theobald P, Guillaumin D, Levy G. Laparoscopic preperitoneal colposuspension for stress incontinence in women. Technique and results of 37 procedures. Surg Endosc 1995; 9:1189–1192. Cooper MJW, Cario G, Lam A, Carlton M. A review of results in a series of 113 laparoscopic colposuspensions. Aust NZ J Obstet Gynaecol 1996; 36:44 – 48. Kung RC, Lie K, Lee P, Drutz HP. The cost effectiveness of laparoscopic versus abdominal Burch in women with urinary stress incontinence. J Am Assoc Gynecol Laparosc 1996; 3:537 – 544. Nieves A. Long-term results of laparoscopic Burch. J Am Assoc Gynecol Laparosc 1996; 3:S35. Radomski SB, Herschorn S. Laparoscopic Burch bladder neck suspension: early results. J Urol 1996; 155:515– 518. Shwayder JM. Laparoscopic Burch cystourethropexy compared with the transperitoneal and extraperitoneal approaches. J Am Assoc Gynecol Laparosc 1996; 3:S46 – S47. Burton GA. A three-year randomized urodynamic study comparing open and laparoscopic colposuspension. Neurourol Urodynam 1997; 16:353 – 354. Lobel RW, Davis GD. Long-term results of laparoscopic Burch urethropexy. J Am Assoc Gynecol Laparosc 1997; 4:341– 345. Papasakelariou C, Papasakelariou B. Laparoscopic bladder neck suspension. J Am Assoc Gynecol Laparosc 1997; 4:185– 189. Su TH, Wang KG, Hsu CY, Wei HJ, Hong BK. Prospective comparison of laparoscopic and traditional colposuspensions in the treatment of genuine stress incontinence. Acta Obstet Gynecol Scand 1997; 76:576 – 582. Das S. Comparative outcome analysis of laparoscopic colposuspension, abdominal colposuspension and vagin*l needle suspension for female urinary incontinence. J Urol 1998; 160:368– 371. Lee CL, Yen CF, Wang CJ, Huang KG, Soong YK. Extraperitoneal colposuspension using CO2 distension method. Int Surg 1998; 83:262 – 264. Miannay E, Cosson M, Lanvin D, Querleu D, Crepin G. Comparison of open retropubic and laparoscopic colposuspension for treatment of stress urinary incontinence. Eur J Obstet Gynecol Reprod Biol 1998; 79:159 – 166. Ross JW. Multichannel urodynamic evaluation of laparoscopic Burch colposuspension for genuine stress incontinence. Obstet Gynecol 1998; 91:55– 59. Saidi MH, Sadler RK, Saidi JA. Extraperitoneal laparoscopic colposuspension for genuine urinary stress incontinence. J Am Assoc Gynecol Laparosc 1998; 5:247 – 252. Fatthy H, El Hao M, Samaha I, Abdallah K. Modified Burch colposuspension: laparoscopy versus laparotomy. J Am Assoc Gynecol Laparosc 2001; 8:99 – 106. Lee CL, Yen CF, Wang CJ, Jain S, Soong YK. Extraperitoneal approach to laparoscopic Burch colposuspension. J Am Assoc Gynecol Laparosc 2001; 8:374 –377. Zullo F, Palomba S, Piccione F, Morelli M, Arduino B, Mastrantonio P. Laparoscopic Burch colposuspension: a randomized controlled trial comparing two transperitoneal surgical techniques. Obstet Gynecol 2001; 98:783 – 788. Ou CS, Presthus J, Beadle E. Laparoscopic bladder neck suspension using hernia mesh and surgical staples. J Laparoendosc Surg 1993; 3:563 – 566. Demco L. Hysterectomy panel discussion. J Am Assoc Gynecol Laparosc 1994; 13:287 – 295. Bass EB, Pitt HA, Lillemoe KD. Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy. Am J Surg 1993; 165:466 –471. Soper, NJ, Brunt LM, Kerbl K. Laparoscopic general surgery. N Engl J Med 1994; 330:409– 419. Levy BS, Hulka JS, Peterson HB. Operative laparoscopy: AAGL membership survey. J Am Assoc Gynecol Laparosc 1994; 14:301 – 314.

20 Insertion of Artificial Urinary Sphincter in Women H. Roger Hadley Loma Linda University, Loma Linda, California, U.S.A.



The artificial urinary sphincter (AUS) is an effective alternative to the urethral sling or periurethral injection therapy for the treatment of urinary incontinence in women as a result of intrinsic sphincteric deficiency (ISD) or type III stress urinary incontinence (1,2). In women with anatomic (type II) urinary incontinence associated with poor bladder neck support (hypermobility), the AUS is rarely inserted in deference to the more commonly used urethral sling or standard bladder neck suspension. Intrinsic sphincter deficiency in women may be associated with or due to scarring following multiple prior anti-incontinence operations, neurologic disorders (myelomeningocele, sacral cord tumor, or peripheral neuropathy), radical pelvic operations (abdominoperineal resection or radical hysterectomy), pelvic radiation therapy, and estrogen deficiency, or senile changes of the urethra and vagin*. Because intrinsic sphincter deficiency leads to inadequate urethral closure, a standard bladder neck suspension is unlikely to alleviate the patient’s stress urinary incontinence. Operative management, therefore, is directed toward improving urethral closure with a suburethral sling, periurethral bulking agents, or insertion of the AUS. The AUS is a manufactured device that includes a pump, a reservoir to store and regulate the pressure of the hydraulic fluid, and a cuff designed to provide a uniform circumferential compression on the urethra and bladder neck (Fig. 1). To empty her bladder the patient cycles the pump component of the AUS which is placed in the subcutaneous tissue of the labia majora. The American Medical System AS-800 is the only artificial sphincter currently commercially available and can be implanted using either a transvagin*l or transabdominal approach. This chapter describes the technique of transvagin*l implantation of the artificial urinary sphincter in the treatment of incontinence due to intrinsic sphincter deficiency (type III stress urinary incontinence).



Evaluation of the incontinent female patient should include a history, physical examination, radiographic evaluation, and urodynamic studies. The patient with genuine stress urinary 319



Figure 1 The AS-800 AUS in a woman. The cuff is placed around the bladder neck, the pressureregulating balloon in the prevesical space, and the pump in the labia majora. (From Ref. 14.)

incontinence due to intrinsic sphincter deficiency will report loss of urine with abdominal straining that may or may not be associated with urgency. Previous anti-incontinence procedures, radical pelvic operations, history of orthopedic or neurologic disorders, and currently used medications (including replacement hormones) constitute important historical information. Physical examination includes measurement of postvoid residual volume and an assessment of vagin*l wall integrity and pelvic floor support. With the bladder filled to near capacity, the patient is assessed for stress urinary incontinence in the supine and/or upright position. Not only is it imperative to witness the loss of urine simultaneous to abdominal straining, but it is also important to make note of the severity of incontinence—i.e., losses of large volumes of fluid with minimal provocation. The Q-tip deflection test is used to assess urethral mobility. Neurologic examination of the lower extremities and perineum is performed to evaluate the lower lumbar and sacral cord segments. Cystourethroscopy is done to assess urethral coaptation, bladder trabeculation, and the unlikely presence of a fistula. Radiographic evaluations may include a standing voiding cystourethrogram with resting and straining views. A well-supported urethra with an open bladder neck not associated with a bladder contraction is consistent with primary urethral insufficiency. Urodynamic studies include a filling cystometrogram and measurement of urethral leak point pressure. Leakage of urine associated with a leak point pressure of ,80 –100 cmH2O in the absence of a detrusor contraction supports the diagnosis of intrinsic sphincter deficiency. Women with severe leakage (e.g., ,40 –50 cmH2O) may need to be identified in a separate category, since these patients do not respond as well to traditional treatments as compared to their counterparts with higher pre-treatment leak point pressures.

Artificial Urinary Sphincter


Video urodynamics, if available, provides a concurrent fluoroscopic and urodynamic assessment that allows a simultaneous and perhaps a more accurate evaluation of the cause and type of urinary incontinence. A.

Patient Selection

Implantation of an AUS is reserved for those who have genuine stress urinary incontinence despite a well-supported bladder neck and no significant bladder instability. If the incontinent patient has concomitant vesical instability, simultaneous pharmacologic or operative management may be required to achieve urinary continence. In the patient with urinary incontinence due to primary urethral insufficiency, conservative measures should be tried before operative intervention. These nonoperative measures include timed voiding, fluid restriction, pelvic floor exercises, systemic or topical estrogens, a-receptor agonists, and anticholinergic medications. If the patient continues to be incontinent despite conservative treatment, placement of the artificial urinary sphincter may be considered. Because the more commonly used modes of therapy—urethral sling and periurethral bulking agents—have not been as successful in patients with severe incontinence and low leak point pressures, the AUS should be seriously considered and, indeed, may be best suited in these patients since it is designed to provide a uniform circumferential compression on the incompetent bladder neck. B.


The artificial urinary sphincter is composed of three parts: the inflatable cuff, the pressureregulating balloon, and the pump (Fig. 1). The cuff is placed circumferentially around the bladder neck, the pressure-regulating balloon is positioned in the prevesical space, and the pump is put in the labia majora. When the pump is squeezed, fluid moves from the cuff to the balloon reservoir. This decompression of the cuff opens the bladder neck and allows the patient to void. After 1 – 2 min the pressure-regulating balloon automatically reinflates the cuff, which then reestablishes urethral coaptation and continence. Three different techniques have been described for the transvagin*l placement of the artificial urinary sphincter (1,3,4). The inherent advantage of the transvagin*l approach is the possibility of dissection of the urethrovagin*l plane, which is often obliterated after previous anti-incontinence procedures. The transvagin*l technique allows dissection of the urethrovagin*l plane under direct vision. A vertical incision is made in the anterior vagin*l wall (Fig. 2). The incision extends from a point midway between the bladder neck and the external meatus to the proximal bladder neck. A plane under the vagin*l wall is created on each side of the incision with sharp dissection. The dissecting scissors are first pointed laterally to the pubis ramus and then upward toward the ipsilateral shoulder of the patient (Fig. 3). Sufficiently thick vagin*l flaps are created in anticipation of closure of the vagin* over the soon-to-be-placed cuff of the artificial urinary sphincter. If the patient has not had a previous bladder neck operation, blunt finger dissection may be performed to separate the endopelvic fascia from its lateral attachments to the pubic rim. The finger should sweep from lateral to medial, creating a window into the retropubic space. In the patient with dense scar tissue, sharp dissection will be required to enter the retropubic space. The urethra and bladder neck can then be separated posteriorly and laterally from the vagin* and the pelvic side wall with sharp and blunt dissection. A similar procedure is followed on the opposite side. The posterior aspect of the bladder neck is dissected free from the underlying anterior vagin*l wall. It is important to mobilize the bladder from the vagin*l wall without extending the



Figure 2 With the patient in the modified dorsolithotomy position, a vertical incision is made in the anterior vagin*l wall. (From Ref. 14.)

vagin*l incision toward the apex of the vagin*. Leaving an intact thick vagin*l wall underneath the bladder neck will lessen the likelihood of cuff erosion into the vagin*. Attention is next directed to the anterior aspect of the proximal urethra or bladder neck to free its attachments from the overlying symphysis pubis. If possible, blunt finger dissection should be used to perform this part of the procedure. However, in the patient who has had a previous retropubic operation, dense scarring may be encountered in the anterior portion of the urethra. Overly aggressive dissection may lead to unintentional bladder opening or urethral tear. The dissection on the anterior side of the urethra may be particularly difficult because of its relative inaccessibility through the transvagin*l approach. To facilitate exposure of the top side of the urethra a separate suprameatal incision may be used. The previously placed Foley catheter is retracted downward, and a small (1 – 2 cm), crescent-shaped incision is made above the external meatus (Fig. 4A). Sharp dissection is then done in the midline below the symphysis pubis (Fig. 4B). After the bladder is allowed to drop away from its attachments to the symphysis, lateral blunt dissection can be easily performed to complete the dissection to the retropubic space previously opened through the vagin*l incision. Thus, a circumferential dissection is completed around the bladder neck. However, if one is readily able to free the urethra from its anterior attachments through the vagin*l incision alone, this suprameatal dissection is not necessary. After the proximal urethra has been freed circumferentially, a broken-back small vascular clamp (Dale femoral-popliteal anastomosis clamp, Pilling 35-3543) is passed around the urethra from the left to right. The cuff-measuring tape is grasped and passed around the urethra (Fig. 5), and the circumference of the urethra is measured. If the circumference is equivocal, it is best to err in favor of a slightly larger cuff size. Using a curved clamp, the appropriate-size cuff of the

Artificial Urinary Sphincter


Figure 3 Using a combination of sharp and blunt dissection, the retropubic space is entered lateral to the bladder neck. (From Ref. 14.)

artificial urinary sphincter is placed around the proximal urethra (Fig. 6). If the pump of the artificial urinary sphincter is to be inserted into the right labium majus, the cuff is withdrawn from right to left. If, however, the pump is to be placed in the left labia majora, the cuff should be withdrawn from left to right. The cuff is then locked in place (see Fig. 6) and rotated 1808 so that the hard-locking button lies on the anterior aspect of the urethra, away from the anterior vagin*l wall (Fig. 7). A 4-cm transverse suprapubic incision is made on the side that the pressure-regulating balloon and pump mechanism will be implanted. The tubing passer is passed antegrade under fingertip guidance from the suprapubic incision lateral to the midline and down to the vagin*l incision on the ipsilateral side of the bladder neck. (This operative step is similar to passing a needle carrier under fingertip guidance during a Pereyra-type bladder neck suspension.) The cuff tubing is attached to the tubing passer and then withdrawn up to the suprapubic incision. The anterior rectus sheath is incised transversely, and the prevesical space is developed adjacent to the bladder. The pressure-regulating balloon is then inserted in the prevesical space. In women, the 51 –60 cmH2O pressure balloon reservoir is routinely used. From the suprapubic incision a subcutaneous tunnel is created through which the pump will be inserted into the labia majora. The pump is passed into the labia majora to the level of the urethra with the deactivation button facing anteriorly. Filling of the cuff and reservoir is performed according to the instructions specified by the manufacturer. The tubings are trimmed to the appropriate lengths and then irrigated to remove any air or debris from the system. The suprapubic and vagin*l wounds are irrigated with copious amount of antibiotic solution. The wounds are then closed in multiple layers with absorbable sutures to ensure good



Figure 4 (A) If dense scarring is encountered anterior to the urethra, a separate incision is made above the urethral meatus. (B) The suprameatal dissection is done in the midline just below the symphysis pubis. (From Ref. 14.)

Artificial Urinary Sphincter


Figure 5 A Penrose drain is placed around the bladder neck to demonstrate the completed circumferential dissection. (From Ref. 14.)

coverage of the prosthesis with healthy overlying tissue. If the integrity of the vagin*l wall appears to be compromised, an interposition of a vascularized flap (e.g., Martius flap) should be considered. The pump is left in the deactivated mode for 6 weeks. A vagin*l gauze pack is placed and removed on the first postoperative day. The Foley catheter is removed on the third postoperative day.



Favorable outcomes of transvagin*l placement of the AUS have been published. Appell reported a series of 34 patients in whom the artificial urinary sphincter was placed through simultaneous vagin*l and abdominal incisions (1). Nineteen patients underwent follow-up of 3 years. The overall continence rate was 100%. Three patients, however, required revisionary operations for inadequate cuff compression and connector leak. Abbassian described the implantation of the artificial urinary sphincter in four patients utilizing the vagin*l incision alone (4). At mean follow-up of 14 months, all patients were dry. The potential advantage of the artificial urinary sphincter over the urethral sling is the capability to place a known circumferential compressive force around the entire urethra rather than a single force on the posterior surface of the urethra. Women with severe leakage (e.g., ,40 – 50 cmH2O) do not respond as well to traditional treatments as compared to their counterparts with higher pretreatment leak point pressures. The AUS may therefore be the preferred treatment in those patients with severe symptoms of stress incontinence associated with very low leak-point pressures.



Figure 6 The cuff of the artificial urinary sphincter is passed around the bladder neck and then locked in place. (From Ref. 14.)

In addition, a decreased likelihood of urinary retention and bladder instability may be associated with the artificial urinary sphincter. The incidence of prolonged postoperative urinary retention after the urethral sling operation has been reported to be up to 10%, especially in patients with a preoperative hypotonic bladder (5). Persistent postoperative frequency and urgency due to bladder instability has been demonstrated in 6 – 18% of patients after placement of the pubovagin*l sling in the treatment of type III stress urinary incontinence (6,7). In our experience of 25 patients who underwent transvagin*l placement of the AS-800 artificial urinary sphincter for primary urethral insufficiency, seven patients had preoperative hypotonic bladder documented on urodynamic studies. Follow-up lasted from 3 to 16 months (mean, 7.3 months). None of the patients developed clinically significant postoperative frequency or urgency. All seven patients were dry and able to void spontaneously with or without abdominal straining. Prolonged (i.e., .1 month) urinary retention requiring intermittent catheterization was not demonstrated by any of the patients who had hypocontractile bladders preoperatively (8). The continence rate of the AUS successfully implanted either by the transvagin*l or transabdominal approach in women who have not had an erosion in either the bladder or vagin* has been very good. A recent series of more than 200 women undergoing a transabdominal placement of the AUS reported a continence rate of .90% with a mean follow-up of 3.9 years. In this same series the explantation rate was 6% (12). Long-term reliability of the artificial sphincter, regardless of the technique of implantation, is reported sparingly in the urological literature. Our experience from the artificial sphincter in both men and women indicates that the revision rate from all causes is 50% at 5 years and .90% at 10 years. Similar 10-year revision rates have been reported from Fulford et al. (13).

Artificial Urinary Sphincter


Figure 7 The cuff is rotated 1808 clockwise so that the hard-locking button lies anterior to the urethra, away from the anterior vagin*l wall. (From Ref. 14.)

Erosion of the AUS, like all nonhuman implantable devices, is a risk that cannot be completely avoided. Extrusion may occur if the pump erodes through the skin of the labium or the cuff erodes into the urethra or the vagin*. Device erosion has been attributed to poor circulation, low-grade infection, technical difficulties, and shifting of the cuff (4). Cuff erosion commonly occurs in patients who have undergone prior pelvic irradiation (9). Our earlier experience included two patients who had been previously irradiated for cervical carcinoma. Both patients developed repeated cuff erosion into the vagin* despite multiple revisionary operations. With the use of a low-pressure-regulating balloon (51 – 60 cmH2O pressure), delayed primary activation of the cuff, and exclusion of the patient with prior pelvic radiotherapy, the incidence of device erosion may be much reduced (1,9). In the past, mechanical malfunction of the artificial urinary sphincter has been common, revision occurring in 31 – 43% of women with the device (10,11). However, since the introduction of the newly improved cuff design and the in situ activation-deactivation control assembly of the AS-800 model in 1983, the incidence of mechanical malfunction has dramatically decreased (2).



Intrinsic urethral deficiency in women with stress urinary incontinence associated with a nonmobile, well-supported urethra and bladder neck is certainly a challenge in management to the urinary incontinence specialist. Many of these patients have undergone previous



unsuccessful anti-incontinence operations. The artificial urinary sphincter is a viable alternative treatment modality to the urethral sling or periurethral injection therapy for these difficult patients. It may be the most appropriate mode of treatment for those patients with severe stress incontinence since these patients have not responded well to the customary urethral slings and periurethral bulking agents. The advantage of the transvagin*l approach in the placement of the artificial urinary sphincter is that it offers the surgeon the ability to dissect through the difficult urethrovagin*l plane under direct vision. In the patient with abundant scar tissue, the addition of a suprameatal incision reduces the likelihood of an inadvertent cystotomy or urethral injury during the anterior dissection of the urethra. With familiarization of the implantation technique, the use of a low-pressure-regulating balloon reservoir (51 –60 cmH2O pressure), delayed primary activation of the cuff, and selective patient criteria (e.g., exclusion of patients with prior pelvic irradiation), the artificial urinary sphincter can result in reasonable long-term social continence in patients with urinary incontinence due to intrinsic urethral insufficiency. In the subgroup of patients with a combination of hypotonic bladder and intrinsic sphincteric incompetence, the artificial urinary sphincter may be the initial treatment of choice over the urethral sling because of its lower incidence of prolonged postoperative urinary retention and vesical instability.

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Appell RA. Techniques and results in the implantation of the artificial urinary sphincter in women with type III stress urinary incontinence by a vagin*l approach. Neurourol Urodyn 1988; 7:613– 619. Webster GD, Perez LM, Khoury JM. Management of type III stress urinary incontinence using artificial urinary sphincter. Urology 1992; 39(6):499– 503. Hadley R. Transvagin*l placement of the artificial urinary sphincter in women. Neurourol Urodyn 1988; 7:292– 293. Abbassian A. A new operation for insertion of the artificial urinary sphincter. J Urol 1988; 140:512 – 513. Blaivas JG, Jacobs BZ. Pubovagin*l fascial sling for the treatment of complicated stress urinary incontinence. J Urol 1991; 145:1214– 1218. Blaivas JG, Olsson CA. Stress incontinence: classification and surgical approach. J Urol 1988; 139:727. McGuire EJ, Bennett CJ, Konnak JA. Experience with pubovagin*l slings for urinary incontinence at the University of Michigan. J Urol 1987; 138:525. Wang Y, Hadley HR. Artificial urinary sphincter in the female: is it procedure of choice for the patient with type III urinary incontinence associated with an acontractile bladder?. J Urol 1992; 147(4):377A. Duncan HJ, Nurse DE, Mundy AR. Role of the artificial urinary sphincter in the treatment of stress incontinence in women. Br J Urol 1992; 69:141. Donovan MG, Barrett DM, Furlow WL. Use of the artificial urinary sphincter in the management of severe incontinence in females. Surg Gynecol Obstet 1985; 161:17. Light JK, Scott FB. Management of urinary incontinence in women with the artificial urinary sphincter. J Urol 1985; 134:476 – 478. Costa P. The use of an artificial urinary sphincter in women with type III incontinence and a negative Marshall test. J Urol 2001; 165(4):1172– 1176. Fulford SCV, Sutton C, Bales G. The fate of the “modern” artificial urinary sphincter with a follow-up more than 10 years. Br J Urol 1997; 79:713– 716. Wang Y, Hadley R. Artificial sphincter: transvagin*l approach. In: Raz, S, ed. Female Urology. 2nd ed. Philadelphia: W.B. Saunders, 1996.

21 Urethral Injectables in the Management of SUI and Hypermobility Sender Herschorn and Adonis Hijaz University of Toronto and Sunnybrook and Women’s Health Sciences Centre, Toronto, Ontario, Canada



Murless, in 1938, first reported on injection of sodium morrhuate around the urethra by (1), and since then various materials have been injected for urinary incontinence as an alternative to surgery. Quackels (2) reported paraffin wax in 1955, and Sachse (3) used sclerosing agents in 1963. The initial results were poor, and significant complications such as pulmonary emboli and urethral sloughing were seen. Polytetrafluoroethylene (Teflon) paste, was first introduced by Berg (4) and then popularized by Politano (5) in the 1970s. Shortliffe et al. (6) published the first report on glutaraldehyde cross-linked collagen, and more recently autologous fat injection (7) has been described. Newer agents, such as silicone microparticles (8) and injectable microballoons, have also been reported (9). Despite a tremendous growth in interest recently in injectable agents, there have been few published prospective randomized trials comparing different agents or injectables to other treatments for SUI. Outcome measures have not been standardized. This article will summarize the properties, published results, and complications of the various agents as well as examine some of the controversies.



It is generally agreed that these agents improve intrinsic sphincter function. Collagen injections have been reported (10,11) to augment urethral mucosa and to improve coaptation and intrinsic sphincter function as evidenced by an increase in posttreatment abdominal leak pressure (12 –14). Initial investigators with collagen (15,16) postulated obstruction as a mechanism of action, but Monga et al. (11) showed that successfully treated patients have an increased area and pressure transmission ratio in the first quarter of the urethra. They suggested that placement of the injectable at the bladder neck or proximal urethra prevents bladder neck opening under stress. Proper placement of the injectable, possibly just below the bladder neck, rather than actual quantity (17) of the agent improves intrinsic sphincter deficiency (ISD). 329


Herschorn and Hijaz

The ideal injectable agent (18) should be easily injectable and conserve its volume over time. If unsuccessful, it should not interfere with subsequent surgical intervention. It should also be biocompatible, nonantigenic, noncarcinogenic, and nonmigratory. To date, no substance has met all of these requirements.



Patients with ISD and normal detrusor function are candidates for injectable agents (19). McGuire et al. (20) identified these patients with the use of abdominal leak pressures to measure the strength of the intrinsic sphincter. Low leak pressures (,65 cmH2O) correlate well with type 3 videourodynamic findings, i.e., a poorly functioning bladder neck and proximal urethra (ISD), and higher leak pressures correlated with types 1 or 2 hypermobility. The presence of ISD is the primary indication for the use of injectable agents in patients with stress incontinence (10). Since ISD can coexist with hypermobility (21), injectables have been administered to patients with hypermobility to improve the ISD component of their incontinence. Furthermore, elderly women with hypermobility, who are poor operative risks, have also been injected (22).



The materials can be administered under local anaesthesia with cystoscopic control as an outpatient procedure. Both the periurethral and transurethral methods are done to implant the agent within the urethral wall, preferably into the submucosa or lamina propria. It is thought that the implant should be positioned at the bladder neck or proximal urethra. Different sites can be chosen such as 3 and 9 o’clock or 4 and 8 o’clock positions. The needle size depends on the viscosity of the injectable. Pre- and postoperative antibiotics are usually administered. The technique of injection is seen in Figures 1 and 2. With the periurethral approach, perimeatal blebs are raised with 1% or 2% lidocaine at the 3 and 9 o’clock or 4 and 8 o’clock positions 3–4 mm lateral to the urethral meatus. A 20F urethroscope with a 308 telescope is inserted into the urethra after instillation of topical urethral lidocaine. The periurethral needle is introduced and advanced parallel to endoscope sheath until its position can be seen cystoscopically just below the bladder neck within the mucosa. Care must be taken to prevent the needle from getting to close to or entering the urethral lumen as rupture of the mucosa and extravasation will occur. Rocking the needle will confirm the position of the tip. If penetration of the mucosa occurs, the needle should removed and repositioned. The substance is injected either unilaterally or bilaterally to create the appearance of “prostatic” lobes. The patient is asked to cough or strain in the supine and then upright position. If leakage still occurs, more agent may be given. If no leakage is seen, the procedure may be terminated. The patient then voids and can be discharged. Acute retention can be treated by insertion of a fine 8F catheter. The implant can also be injected transurethrally through the cystoscope with specially designed needles. Teflon, silicone microparticles, and fat, owing to their high viscosity, may require the use of injection guns. A.


Glutaraldehyde cross-linked collagen or Gax-collagen is a highly purified suspension of bovine collagen in normal saline containing at least 95% type I collagen and 1– 5% type III

Urethral Injectables for SUI


Figure 1 Periurethral collagen injection. The 20F cystoscope with a 308 lens is positioned in the urethra while the substance is injected into the bladder neck region.

collagen (23). This cross-linking makes the Gax-collagen resistant to the fibroblast-secreted collagenase. As a result of this, the Gax-collagen is only very slightly resorbed. The implant causes no inflammatory reaction or granuloma formation and is colonized by host fibroblasts and blood vessels. It is not known to migrate. However, it does degrade over time and is replaced by host collagen, to explain its persistence (23). Since 2 –5% of patients (24) are sensitized to collagen through dietary exposure, all patients must undergo a skin test into the volar aspect of the forearm 30 days prior to treatment. Positive responders should be excluded. 1. Collagen Results Numerous reports of its efficacy, safety, ease of administration, and relative lack of morbidity have appeared since the first description of collagen injections for urinary incontinence. Our original report, with short-term follow-up of 6 months (12), showed a cured and improved rate of 90.3%. With longer follow-up the success rate decreased, but there were still long-term cures. Table 1 lists various reported series.


Herschorn and Hijaz

Figure 2 (a) Cystoscopic view of the open bladder neck region prior to injection. (b) Collagen has been injected via the periurethral route on the patient’s left side. Note the intraluminal bulking effect of the agent.

Persistence of the implant itself has been demonstrated with magnetic resonance imaging of the urethra at intervals of up to 22 months after injection although the measured volume was less than that injected (25). Early results are generally good with success rates of 72– 100% (Table 1). Maintenance of good results in the long term may be from durability of the initial procedure itself or from reinjections with additional collagen. It is important for authors to differentiate the durability of the original procedure(s) from reinjections or top-ups by reporting the follow-up period starting from after the last injection.

16 25 44

11 50 17 137 12 60


Kieswetter et al. (27) Eckford and Abrams (15) O’Connell et al. (28)

Moore et al. (29) Winters and Appell (13) McGuire and Appell (10)

Richardson et al. (14)

Faerber (22) Monga et al. (11)


No. pts.

Stricker and Haylen (26)



Types 1 and 3 ISD Mobile ISD Type 1 Some hypermobile

Not specified Not specified 42 with ISD 2 hypermobile


Type of incontinence

Table 1 Comparison of Collagen Parameters and Results

2 .12 .12 .12 10.3 (Range 3 – 24) 3 (N ¼ 59) 12 (N ¼ 54) 24 (N ¼ 29) 46 (10– 66 after 1st injection)

Mean: 11 Range: 1 –21 9 3 1 –2(longest 7)

Follow-up (mo.)

(17) (34) (17) (40) (37) (20) (43)


7 (44) 4 (16) 8 (18)

20 (40)

(continued )

7 (17)

2 (18) 2 (4) 6 (35) 29 (19) 0

2 (12) 5 (20) 16 (37)

7 (14)

No. pts. No. pts. improved (%) failed (%)

1 (9) 7 48 (96) dry or socially continent 8 (47) 3 63 (46) 47 10 (83) 2 27 (46) 24 22 (40) 20 14 (48) 6 17 (40) 18

7 (44) 16 (64) 20 (45)

21 (42)

No. pts. dry (%)

Urethral Injectables for SUI 333


94 21 107 103 63

90 40

Smith et al. (31) Khullar et al. (17) Swami et al. (32) Cross et al. (33)

Groutz et al. (34)

Bent et al. (35) Corcos and Fournier (36)

No. pts.

Herschorn et al. (30)


Table 1 Continued

Type Type Type Type

1&2 1 (8) 2 (20) 3 (12)

Type 3

Type 1: 54 Type 2: 67 Type 3: 60 Type 3 Not specified Some hypermobile Type 3

Type of incontinence

12 Av 52; 47 – 55

Mean 6.4 þ 4.9

Mean: 22 (Range 4 – 69) .¼24 (N ¼ 62) .¼36 (N ¼ 25) Median: 14 24 (minimum) 24 (minimum) Median: 18 (Range 6 – 36)

Follow-up (mo.)

19 (21%) 12 (30%)

42 (23) 27 (43.5) 13 (52) 36 (38.3) 10 (48) 27 (25) Substantially improved 103 (74) 13%

No. pts. dry (%)

(52) (46.8) (32) (28.7) (9) (40) (20) 10% good 17% fair 42% poor 19 (21%) 16 (40%)

94 29 8 27 2 43 29

(25) (9.7) (16) (33) (43) (35) (6)

62 (58%) 12 (30%)


45 6 4 31 9 37 7

No. pts. No. pts. improved (%) failed (%)

334 Herschorn and Hijaz

Urethral Injectables for SUI


Longer-term results of more than 1 –2 years vary from 57%, cure and improved (17), to 94% (36). Most patients need one or two treatment sessions with means of 5.6 – 15 cc collagen. Since patients are treated at different times and durations of follow-up vary, the Kaplan-Meier curve can be useful to display the persistence of a good result. In our series (30), the probability of remaining dry was 72% at 1 year, 57% at 2 years, and 45% at 3 years (Fig. 3). Winters and Appell (13) also reported a similar 50% rate of complete continence in the multicentre trial after 2 years. Corcos and Fournier reported a 4-year follow-up with 40% improvement and 30% cure rates (36). Additional administration of collagen usually resulted in restoration of continence, and this has to be factored into the reporting. Berman and Kreder (37) analyzed the cost effectiveness of collagen versus sling cystourethropexy for type 3 incontinence. They concluded that surgery was more cost effective than collagen.


Collagen and Hypermobility

The use of collagen for patients with hypermobility has been reported. Moore et al. (29) included patients with both type 1 and type 3 abnormalities. Faerber (22) treated elderly patients with type 1 abnormality. In the report by McGuire and Appell (10), the results at .1 year in women with ISD were similar to those in women with hypermobility, although there were far more women with ISD. However, Appell (19) subsequently reported that these patients with hypermobility all required bladder neck surgery within 2 years. Monga et al. (11) included patients with hypermobility and found that cure rates were not reduced for women with up to 2.5 cm of movement. In our series of 181 patients there was no significant difference in outcome in patients with or without hypermobility (30). Steele et al. (38) found that urethral mobility did not significantly affect the success rate. As a matter of fact, four of six patients with urethral hypermobility were dry at the 6-month follow-up examinations; however, among the 19 women

Figure 3 Durability: Kaplan-Meier curve showing durability of cure of incontinence after the last collagen injection in 78 patients. (From Ref. 30.)


Herschorn and Hijaz

without hypermobility, only a 32% remained dry. Corcos and Fournier found no difference between patients with and without bladder neck hypermobility in their 4-year follow-up on 40 patients (36). 3.

Collagen Complications

Treatment-related morbidity has been minimal. Urinary retention ranges from 1% to 21% (12,13,19) and can be managed with intermittent catheterization or short-term foley. Urinary tract infection occurs in 1– 25% (12,13,19). Extravasation resolves quickly with flushing away of the dilute collagen suspension and sealing over of the small needle site. Hematuria can occur in 2% of patients (19). Another rare complication is periurethral abscess formation (39). Other complications include de novo instability, seen in 11 of 28 elderly women (39%) treated by Khullar et al. (17). Stothers et al. reported de novo urgency with urgency incontinence in 43 of 337 patients (12.9%), 21% of whom did not respond to anticholinergics (40). Another rare complication is a reaction in the previously negative skin test site following a urethral collagen injection (24). This occurred in three patients (1.9%) and was associated with arthralgias in two. This reaction has been reported before in the dermatologic literature (41), and two negative pretreatment skin tests have been suggested to prevent it. The potential for hypersentivity reactions is present since antibody production is stimulated by collagen injection (42). B.

Polytetrafluoroetylene Paste (PTFE, Teflon, Urethrin)

Polytetrafluoroetylene Paste (Teflon) is composed of equal parts Teflon paste and glycerine with polysorbate 20 (43). Teflon is a resin polymer with a very high molecular weight and high viscosity, and is composed of small particles (40 mm in diameter). It is inert and stable, and does not induce an allergic response. However, it does cause a local inflammatory response with histiocytes phagocytizing the particles and coalescing to form foreign body giant cells and a granuloma. There is also fibrous tissue ingrowth that adds to the bulk formed by the Teflon. Owing to the small particle size, Malizia et al. (44) also showed distant migration of teflon particles to pelvic nodes, lung, brain, and kidneys of experimental animals. Teflon paste has been used to treat urinary incontinence since 1964, but it was not reported until 1975, by Berg (4). Since that time, numerous reports relating to its use in treating incontinence have appeared in the literature. Although not approved in the United States, Teflon has been approved in Canada and in other countries. It may be injected via the periurethral route and volumes of up to 10 –20 cc are reported. The procedure is done under local or spinal anesthesia, and repeats may be done after 6 months. We have modified the procedure by injecting small amounts (2.5 cc) via the periurethral approach under local anesthetic (45). Heating the Teflon reduces its viscosity and allows injection without a gun. 1.

Teflon Results

Table 2 lists various series. There are wide-ranging outcomes with longer-term series showing poorer results (33 –76% cure and improved) than those of short-term series (57 – 86%) (46 –54). 2. Teflon Complications Since relatively large volumes of Teflon have been injected with the patient under general anesthesia, the incidence of urinary retention at 25% (46) is higher than that of collagen. Irritative voiding symptoms have also been seen transiently in 20% (48). Urinary infection is

Urethral Injectables for SUI


Table 2 Teflon Results for Female Stress Incontinence Study

No. pts.

Follow-up (mo.)

Pts. dry (%)

Politano et al. (46) Lim et al. (47) Schulman et al. (48) Deane et al. (49) Beckingham et al. (50) Harrison et al. (51) Lotenfoe et al. (52) Lopez et al. (53) Vesey et al. (54) Herschorn and Glazer (45)

51 28 56 28 26 36 21 74 36 46

6 — 3 3 – 24 36 61 11 31 9 (3 – 36) 12

26 6 39 9 2 4 8 41 20 14

(51) (21) (70) (32) (7) (11) (38) (56) (56) (31)

Pts. improved (%) 10 9 9 8 7 8 4 15 4 19

(20) (33) (16) (28) (27) (22) (19) (20) (11) (41)

Pts. failed (%) 15 (29) 13 (46) 8 (4) 11 (40) 17 (66) 24 (67) 9 (43) 18 (24) 12 (33) 13 (28)

rare at 2% (47). Perineal discomfort may occur in 5% (46), and transient fever in 10– 15% of patients. Perforation and extravasation can occur and, if recognized at the time of injection, the Teflon should be removed. Although Teflon particles can migrate (44), only one case of clinical significance has been reported in the literature in humans. Claes et al. (55) described a woman previously treated with large volumes of periurethral Teflon for urinary incontinence who later presented with lymphocytic alveolitis and fever. Light microscopy showed Teflon particles in the lungs. She was treated successfully with steroids. Mittleman and Marraccini (56) reported an incidental finding of postmortem interstitial pulmonary granulomas in a previously asymptomatic man who had received Teflon. Kiilhoma et al. (57) reported three complications out of 22 women—a sterile periurethral abscess, a urethral diverticulum, and a urethral granuloma—that all required surgical intervention. In another case, the material migrated into the bulbar corpus spongiosum causing perineal pain for 3 months necessitating medication for pain relief (58). Although neoplastic transformation was hypothesized (44), there has never been a clinical occurrence reported. Furthermore, in a long-term rat study, Dewan et al. (59) demonstrated no increase in tumor risk and no tumors found at the injection site. Despite the potential for complications with Teflon the actual rate of reported problems is low. However, Teflon is rarely used as an injectable now. C.

Autologous Fat

Autologous fat has been used for aesthetic and defect reconstruction since the 1980s (60). Although fat is biocompatible and readily available, 50–90% of the transferred adipose tissue graft may not survive (61). Graft survival depends on minimal handling, low suction pressure during liposuction, and the use of large-bore needles. Smaller grafts survive better than larger ones (62). The procedure involves harvesting abdominal wall fat by liposuction either under local (63) or general anesthesia (64). The injection is usually carried out via the periurethral route with a 16- or 18-gauge needle. Postprocedure care may involve intermittent catheterization or even a suprapubic tube (64). 1.

Autologous Fat Results

A number of reports of urethral fat injections have been published and appear in Table 3. Most of the series report short-term results with success apparently lower than that of other injectables,


Herschorn and Hijaz

Table 3 Results of Autologous Fat Injection


No. pts.

Follow-up (mo.)

Cervigni and Panei (7) Santarosa and Blaivas (65) Trockman and Leach (63) Haab et al. (66) Su et al. (64)

14 12 32 45 26

Palma et al. (67)


9.7 11 6 7 Mean 17.4; range 12 – 30 12

No. pts. dry (%) 8 7 4 6 13

(57) (58) (12) (13) (50)

No. pts. No. pts. improved failed (%) (%) 4 (29) 14 (44) 13 (29) 4 (15)

2 5 14 26 9

(14) (42) (44) (58) (35)

1 injection: 4/13 (34) 2 injections:11/17 (67)

apart from the study of Su et al. (64) with a follow-up of more than 12 months. Palma et al. (67) showed that repeat injections improved the cure rate from 31% to 64%. Haab et al. (66) reported a comparative study with collagen. After a mean of 7 months, 13% of the women with fat injection were cured versus 24% of the women with collagen injections. The subjective improvement rate was also higher with the collagen. Lee and colleagues reported a randomized double-blind study of autologous fat versus saline injection (68). At 3 months, six of 27 (22.2%) and six of 29 (20.7%) women were cured or improved in the fat and saline groups, respectively. In this study periurethral fat injection did not appear to be more efficacious than placebo in treating stress urinary incontinence. 2. Autologous Fat Complications Reported complications are similar to other injectables with urinary infection, retention, hematuria, and extravasation. Additional problems, such as pain, with donor site, the abdominal wall, hematomas, and infection may also be seen. Other noteworthy complications are urethral pseudolipoma (69) and fat embolism (39), one of which was fatal (70). D.

Silicone Microimplants

Silicone microimplants (8) are solid polydimethylsiloxane (silicone rubber) particles suspended in a nonsilicone carrier gel that is absorbed by the reticuloendothelial system and excreted unchanged in the urine. Since 99% of the particles are between 100 and 450 mm in diameter, the likelihood of migration is low. Henly et al. (71) demonstrated distant migration of small particles, ,70 mm, but no migration of particles .100 mm in diameter. Although there was a typical histiocytic and giant cell reaction within the injection site, there was no granuloma formation in response to the larger particles. Since the substance is quite viscous, it must be injected with an injection gun and a 16-gauge tip transurethral needle. 1. Silicone Microimplant Results Hariss et al. (8) reported on 40 patients followed for a minimum of 3 years at which time 16 (40%) were dry, 7 (18%) were improved, and 17 (42%) failed. Twelve of the 16 required one injection, and four needed two injections to become dry. Sheriff et al. (72) reported an overall success of 48% in 34 patients after unsuccessful stress incontinence surgery, and Koelbl et al. (73)

Urethral Injectables for SUI


reported a 60% success rate in 32 women after 12 months but noted a time-dependent decrease in success. Radley et al. (74) reported a success rate of 61% (19.6% cured and 41.1% improved) in 60 women after a mean of 19 months. Barranger et al. (75), in a group of 21 patients, reported a dry rate of 19%, improved rate of 38%, and failure rate of 52% at a median follow-up of 31 months. Interestingly, they did not observe a time-dependent decrease in results.

2. Silicone Microimplant Complications Self-limited side effects of hematuria, dysuria, frequency, and retention have been reported in a minority of patients. The lack of a granulomatous reaction and migration of the large silicone particles may provide some benefit over Teflon, although no long-term data are available. Despite the laboratory and clinical evidence of safety with the large particles concerns still exist about the small silicone particle migration and long-term tissue response to the injection (71).


Other New Injectables

Calcium hydroxylapatite, which is a normal constituent of bone, can be manufactured into particles of a spherical mean diameter of 100 mm. There is one report of its use in 10 women with ISD and limited hypermobility (76). After 1 year, seven reported substantial improvement, two improved, and one had no change. No significant complications were reported. Another new synthetic agent, Durasphere, is composed of nonabsorbable pyrolytic zirconium oxide beads suspended in a carrier gel. The nonreactive beads range in size from 251 to 300 mm. Lightner et al. (77) reported results of a randomized trial compared to bovine collagen. At 1 year after the last treatment, 49 (80.3%) of 61 women in the Durasphere group had an improvement in Stamey continence grade of 1 or more, compared with 47 (69.1%) of 68 women in the collagen group. The difference was not statistically significant. There was also no difference in number of injections or pad weight test. However, the injected initial and repeat injection volume of Durasphere was significantly less than those of collagen. Adverse events were similar, but more women had posttreatment urgency and acute retention with Durasphere. Pelvic x-rays taken at 1 and 2 years after injection showed stability of the bulking agents at the injection site. This suggests potential durability. In another, small series of 13 women, Pannek and colleagues (78) reported a decline in success from 76.9% at 6 months to 33% at 12 months. In contast to the previous study, they demonstrated particle migration locally and to distant sites on follow-up plain x-rays.



To obviate the degradation and movement of injectable materials, Atala and coworkers (79) developed a self-detachable implantable balloon system. The balloon is a silicone elastomer with a check valve that prevents escape of the solution that is injected at the time of implant. The filling solution is a biocompatible cross-linked hydrogel that maintains its volume within the silicone shell. The balloons are inserted into the submucosal area, usually periurethrally, with cystoscopic control. Pycha et al. (9) reported that eight (42%) of 19 women were dry and seven (36.8%) were improved after a mean of 14.4 months. The patients with hypermobility had a poor outcome. Rare complications included bladder instability and balloon extrusion.



Herschorn and Hijaz


Considerable progress has been made since the introduction of collagen injections. Injectable agents are used for buttressing the ISD component of the incontinence, but patients with concomitant hypermobility may benefit as well. They have also been administered to elderly patients who were not surgical candidates. However, there are still a number of areas in which further study is needed. Durability is a concern. Although long-term successes have been reported with collagen and Teflon, the results of both deteriorate over time. Similarly autologous fat and silicone microimplants yield poorer long-term than short-term results. Comparisons of injectables and injectables to surgery have been done to a limited degree and prospective studies have yet to be reported. Despite the ease of the technique and the attractiveness to patients of an outpatient procedure that can be repeated if necessary, the cost-effectiveness of injectable agents relative to other treatments, such as newer, minimally invasive surgical procedures, still has to be addressed. Safety of the material is also a concern. All of the injectables have excellent safety profiles, although the risk of migration and granuloma formation with Teflon has prevented its widespread use. Rare but serious complications have also been reported with collagen and autologous fat. The long-term risks of silicone microparticles, carbon beads, and balloons are unknown. Longer-term and comparative studies may settle these issues. An exciting experimental model of using injected muscle derived cells into the bladder and urethra has been reported (80). There was persistence of the injected muscle cells compared to injected collagen. This may ultimately lead to additional treatments for stress incontinence. Despite the shortcomings of the technology, the lack of long-term data, and the continuing need for an ideal agent, injectables are a viable minimally invasive alternative. Furthermore, since they do work in patients with hypermobility, this has lead to an increase our knowledge of the pathophysiology of stress incontinence. The two major components in stress incontinence, ISD, and hypermobility can be considered as interdependent and not separate entities. The relative importance of each component in any patient is variable, so the result of bulking in one patient with hypermobility may not the same as that in another. Other than the challenges mentioned above, it would be beneficial to identify factors in patients with hypermobility that would predict for success with injectables. More work also needs to be done to find out whether results can be improved by injecting the agent at sites other than the bladder neck.

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Murless BC. The injection treatment of stress incontinence. J Obstet Gynaecol Br Emp 1938; 45:67– 73. Quackels R. Deux incontinences apre`s ade´nectomie gue´ries par injection de paraffine dans la pe´rine´e. Acta Urol Belg 1955; 23:259– 262. Sachse H. Treatment of urinary incontinence with sclerosing solutions. Indications, results, complications. Urol Int 1963; 15:225 – 244. Berg S. Polytef augmentation urethroplasty. Correction of surgically incurable urinary incontinence by injection technique. Arch Surg 1973; 107:379– 381. Politano VA, Small MP, Harper JM, Lynne CM. Periurethral Teflon injection for urinary incontinence. J Urol 1974; 111:180– 183. Shortliffe LMD, Freiha FS, Kessler R, Stamey TA, Constantinou CE. Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. J Urol 1989; 141:538– 541.

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Cervigni M, Panei M. Periurethral autologous fat injection for type III stress urinary incontinence. J Urol 1993; 149(Part 2):403A. Harriss DR, Iacovou JW, Lemberger RJ. Peri-urethral silicone microimplants (Macroplastique) for the treatment of genuine stress incontinence. Br J Urol 1996; 78:722 – 728. Pycha A, Klingler CH, Haitel A, Heinz-Peer G, Marberger M. Implantable microballoons: an attractive alternative in the management of intrinsic sphincter deficiency. Eur Urol 1998; 33:469– 475. McGuire EJ, Appell R. Transurethral collagen injection for urinary incontinence. Urology 1994; 43:413– 415. Monga AK, Robinson D, Stanton SL. Periurethral collagen injections for genuine stress incontinence. Br J Urol 1995; 76:156 – 160. Herschorn S, Radomski SB, Steele DJ. Early experience with intraurethral collagen injections for urinary incontinence. J Urol 1992; 148:1797 – 1800. Winters JC, Appell R. Periurethral injection of collagen in the treatment of intrinsic sphincter deficiency in the female patient. Urol Clin North Am 1995; 22:673 – 678. Richardson TD, Kennelly MJ, Faerber GJ. Endoscopic injection of glutaraldehyde cross-linked collagen for the treatment of intrinsic deficiency in women. Urology 1995; 46:378 –381. Eckford SD, Abrams P. Para-urethral collagen implantation for female stress incontinence. Br J Urol 1991; 68:586 –589. Appell RA. New developments: injectables for urethral incompetence in women. Int Urogynecol J 1990; 1:117– 119. Khullar V, Cardozo LD, Abbott D, Anders K. GAX collagen in the treatment of urinary incontinence in elderly women: a two year follow up. Br J Obstet Gynaecol 1997; 104:96– 99. Kershen RT, Atala A. New advances in injectable therapies for the treatment of incontinence and vesicoureteral reflux. Urol Clin North Am 1999; 26:81– 94. Appell RA. Periurethral injection therapy. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, eds. Campbell’s Urology. 7th ed. Philadelphia: W.B. Saunders, 1998:1109 – 1120. McGuire EJ, Fitzpatrick CC, Wan J, Bloom D, Sanvordenker J, Ritchey M, Gormley EA. Clinical assessment of urethral sphincter function. J Urol 1993; 150:1452 –1454. Raz S, Little N, Juma S. Female urology. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED, eds. Campbell’s Urology. 6th ed. Philadelphia: W.B. Saunders, 1992:2782 – 2828. Faerber GJ. Endoscopic collagen injection therapy in elderly women with type I stress urinary incontinence. J Urol 1996; 155:512– 514. Remacle M, Bertrand B, Eloy P, Marbaix E. The use of injectable collagen to correct velopharyngeal insufficiency. Laryngoscope 1990; 100:269. Stothers L, Goldenberg SL. Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence. J Urol 1998; 159:1507– 1509. Carr LK, Herschorn S, Leonhardt C. Magnetic resonance imaging of intraurethral collagen injected for stress urinary incontinence. J Urol 1996; 155:1253 – 1255. Stricker P, Haylen B. Injectable collagen for type III female stress incontinence: the first 50 Australian patients. Med J Aust 1993; 158:89 – 91. Kieswetter H, Fischer M, Wo¨ber L, Flamm J. Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. Br J Urol 1992; 69:22 – 25. O’Connell HE, McGuire EJ, Aboseif S, Usui A. Transurethral collagen therapy in women. J Urol 1995; 154:1463 – 1465. Moore KN, Chetner MP, Metcalfe JB, Griffiths DJ. Periurethral implantation of glutaraldehyde crosslinked collagen (contigen?) in women with type I or type III stress incontinence: quantitative outcome measures. Br J Urol 1995; 75:359– 363. Herschorn S, Radomski SB. Collagen injections for genuine stress urinary incontinence: patient selection and durability. Int Urogynecol J 1997; 8:18– 24. Smith DN, Appell RA, Winters JC, Rackley RR. Collagen injection therapy for female intrinsic sphincteric deficiency. J Urol 1997; 157:1275 – 1278. Swami S, Batista JE, Abrams P. Collagen for female genuine stress incontinence after a minimum 2-year follow-up. Br J Urol 1997; 80:757 – 761.

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Herschorn and Hijaz Cross CA, English SF, Cespedes RD, McGuire, E