SEXUAL MEDICINESEXUAL DYSFUNCTIONS

IN MEN AND WOMEN

2nd International Consultation on Sexual Dysfunctions - Paris Co-Sponsored by

International Consultation on Urological Diseases (ICUD)International Society of Urology (SIU)

International Society for Sexual and Impotence Research (ISSIR)

Edition 2004

T.F. LUE - R. BASSON - R. ROSEN -F. GIULIANO - S. KHOURY - F. MONTORSI

EDITORS

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ISBN 0-9546956-0-7

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FOREWORD

The first International Consultation on Erectile Dysfunction held in Paris, France July 1999 wasa milestone in the history of scholarly research in men’s sexual function and dysfunction. The pro-ceedings of the Congress,” Erectile Dysfunction: 1st International Consultation on Erectile Dys-function” has become the most quoted reference on men’s sexual dysfunction in the world.

The ensuing years have seen an explosion of interest in both men’s and women’s sexual functionand dysfunction. There are numerous scientific articles reporting topics from molecular biologyto epidemiology to surgical treatments from all corners of the world. The Second InternationalConsultation inherited this great tradition and expanded the agenda to cover and update the know-ledge related to function and dysfunction of both genders. This proceeding is thus correctlynamed “Sexual Medicine” with the first volume dedicated to men’s sexual function and dysfunc-tion and the second to women’s sexual health and dysfunction.

The more than 200 members of the 19 committees are all internationally known scholars andexperts from the 5 continents of the globe. This marvelous proceeding is the product of 4 prepa-ratory meetings, 4 days of presentations, debates and discussions in Paris and numerous hours ofhard work of the committee members and their committee chairpersons. Besides the committeeson male-specific conditions such as penile prosthesis, Peyronie’s disease and penile reconstruc-tion, all other committees are charged to address issues related to both men and women. There-fore, there is a welcomed huge expansion on the findings of research related to women’s sexualfunction and dysfunction in this book. Although the common theme is an update on the scienceand expert opinion, individual committees have the freedom to add different flavors to its styleand content- making it a truly world effort in this endeavor. Although evidence-based medicine isthe guiding principle in selecting and analyzing articles, consensus expert opinion and geogra-phic, religious and cultural factors are also taken into consideration in forming the recommenda-tions.

Besides updated information on both men’s and women’s sexual health issues and dysfunction,several notable topics are new to this book. These include: 1) Quantitatie research vs. evidencebased medicine; 2) Male Sexual Dysfunction Scale (MSDS) - an important project commissionedby the International Consultation; 3) a brief psychosexual evaluation questionnaire which givesthe clinicians a user-friendly tool to properly evaluate the psychosexual aspect of the patient; 4)brain imaging; and 5) greatly expanded coverage of sexual dysfunction in women.

This tremendous world-wide task would be impossible without the vision of the InternationalConsultation, the generous support of various organizations and industry and the flawless coor-dination by Professor. Saad Koury and his staff. We are also indebted to the important contribu-tions from all committee members and chairpersons and the 4 vice chairs of this Congress: Drs.Francois Giuliano, Raymond Rosen, Rosemary Basson and Francesco Montorsi.

A. Jardin - T.F. Lue

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Some of the members of the international committeesParis - June

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EDITORS

T.F. Lue (USA),

F. Giuliano (France),

S. Khoury (France),

F. Montorsi (Italy),

R. Rosen (USA)

MEMBERS OF THE COMMITTEES(Alphabetical order - Chairmen in bold print)

ABDO C. Brazil 9ADAIKAN G. Singapore 14ADAMS M Canada 10AKKUS E. Turkey 8ALTER G. U.S.A. 8ALTHOF S. U.S.A. 2ALTHOF S. U.S.A. 16AMAR E. France 4ANDERSSON K.E. Sweden 15ANGULO J. Spain 11ARGIOLAS A. Italy 15AUSTONI E. Italy 13BANCROFT J. U.S.A. 16BARADA J. U.S.A. 13BASSON R. Canada 16BAUM M. U.S.A. 10BAUMEISTER R. U.S.A. 16BECHER E. Argentina 14BINIK I. Canada 16BIVALACQUA T. U.S.A. 10BONDIL P. France 3BOSCH R. Netherlands 1BROCK G. Canada 14BRODERICK G. U.S.A. 5BROTTO L. U.S.A. 16BURNETT A. U.S.A. 15BUVAT J. France 12CARRIER S. Canada 14CARSON C. U.S.A. 14CATANIA J. U.S.A. 1CELLEK S. U.K. 11CHEN K. China 15CHEVRET-MEASSON M. France 2CHOI H.K Korea 13CHRIST G. U.S.A. 14CLAYTON A. U.S.A. 5COOLEN L. U.S.A. 10CORBIN J.D. U.S.A. 14

CUZIN B. France 5DABEES K. Egypt 3DAVIS S. Australia 12DEAN J. U.K. 3DEROGATIS L. U.S.A. 5DONATUCCI C. U.S.A. 6EARDLEY U.K. 14ESCHENBACH D. U.S.A. 16FOURCROY J. U.S.A. 3FUGL-MEYER A. Sweden 1FUGL-MEYER K. Sweden 1GIAMI A France 17GINGELL C. U.K. 3GIRALDI A. Denmark 7GLINA S. Brazil 6GOH V. Singapore 12GOLDSTEIN I. U.S.A. 7GONZALES-CADAVID N. U.S.A. 11GOOREN L.J. Netherlands 12GRAHAM C Canada 17GUAY A. U.S.A. 12GUESS M. U.S.A. 6HACKETT G. U.K. 4HARTMAN U. Germany 2HATZICHRISTOU D. Greece 5HEATON J. Canada 11HEDLUND P. Sweden 10HEDLUND H. Norway 14HEIMAN J. U.S.A. 6HELLSTROM W. U.S.A. 13HIRSCH M. U.S.A. 6HULL E. U.S.A. 9HUTTER D. U.S.A. 14HYDE J.S. U.S.A. 6INCROCCI L. Netherlands 9JACKSON G. U.K. 14JAROW J. U.S.A. 4JORDAN G.H U.S.A. 8

JÜNEMANN K.P Germany 14KADIOGLU A. Turkey 7KAUFMAN J.M. Belgium 12KIM Y.C. Korea 12KIMOTO Y. Japan 4KINGSBERG S. U.S.A. 3KOTHARI P. India 3KRISNAMURTI S. India 13LAAN E. Netherlands 16LAUMANN E. U.S.A. 1LEBRET T. France 8LEIBLUM S. U.S.A. 2LEIBLUM S. U.S.A. 16LEJEUNE H. France 12LEVIN R. U.K. 9LEVINE S.B. U.S.A. 2LEVINE L.A. U.S.A. 8LEWIS R. U.S.A. 1LIN C-S U.S.A. 14LITWIN M. U.S.A. 5LIZZA E. U.S.A. 1MARSON L. U.S.A. 7MARTIN-MORALES A.M. Spain 1MAZER N. A. U.S.A. 12MC KENNA K. U.S.A. 10MC VARY K.T. U.S.A. 14MCCABE M. Australia 2MCCULLOUGH A. U.S.A. 14MCMAHON C. Australia 9MESTON C. U.S.A. 9MEULEMAN E. Netherlands 5MILLS T.M U.S.A. 15MIRONE V. Italy 4MONCADA I. Spain 13MONTAGUE K. U.S.A. 6MONTORSI F. Italy 6MORALES A. Canada 12MOREIRA E. Brazil 1MULCAHY J. U.S.A. 13MULHALL J. U.S.A. 8NAPPI R. Italy 7NEHRA A. U.S.A. 14O’LEARY M. U.S.A. 5OKUYAMA A. Japan 3OSWALDO R. Brazil 2PADMA-NATHAN H. U.S.A. 14PARK K. Korea 10PERELMAN M. U.S.A. 9PEROVIC S. Serbia 8PESCATORI E. Italy 10PFAUS J. Canada 7PICKARD R. U.K. 11PLAUT M. U.S.A. 2POPAY J. U.K. 5POPAY J U.K. 17

PORST H. Germany 14PRYOR J. U.K. 8QUIRK F. U.K. 5RAJFER J. U.S.A. 10RALPH D. U.K. 8REDMOND G. U.S.A. 16RICHTER S. Israël 4ROSEN R. U.S.A. 5ROSEN R. U.S.A 17ROWLAND D. U.S.A. 9RUBIO AURIOLES E. Mexico 3SADOVSKY R. U.S.A. 5SAENZ DE TEJADA I. Spain 11SALONIA A. Italy 7SANDERS S. U.S.A. 17SATO Y. Japan 10SCHMIDT A. South Africa 4SCHULMAN C.C. Belgium 14SCHULTHEISS D. Germany 13SCHULTZ W.C. Netherlands 16SEFTEL A. U.S.A. 5SEGRAVES R.T. U.S.A. 6SHABSIGH R. U.S.A. 4SHARLIP I. U.S.A. 14SHIFREN J.L. U.S.A. 12SIMON A. U.S.A. 12SIMONSEN U. Denmark 11SOHN M. Germany 13STACKL W. Austria 8STEERS W.D. U.S.A. 15STIEF C.G. Germany 14STUCKEY B. Australia 9TAN H.M. Malaysia 12TELOKEN C. Brazil 14TIEFER T. U.S.A. 17TORRES L.O. Brazil 12TRAISH A. U.S.A. 7UGARTE F. Mexico 3UTIAN W. U.S.A. 16VAN LANKVELD J. Netherlands 16VAN LUNSEN R. Netherlands 7VARDI Y Israel 7VELA NAVARRETE R. Spain 3WAGNER G. Denmark 3WALDINGER M.D. Netherlands 9WESSELLS H. U.S.A. 13WESSELMANN U. U.S.A. 16WYATT G. U.S.A. 16WYATT L. U.S.A. 16WYLIE K. U.K. 2WYLLIE M. U.K. 6XIN Z.C. China 9YAFFE L. U.S.A. 4

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1. Definitions, Classification and Epidemiologyof Sexual Dysfunctions

BOSCH R. The NetherlandsCATANIA J. U.S.A. FUGL-MEYER A. Sweden FUGL-MEYER K. Sweden LAUMANN E. U.S.A.LEWIS R. U.S.A.LIZZA E. U.S.A.MARTIN-MORALES A.M. SpainMOREIRA E. Brazil 2. Psychological and Interpersonal Dimension

of Sexual Functions and Dysfunctions ALTHOF S. U.S.A.CHEVRET-MEASSON M. France HARTMAN U. GermanyLEIBLUM S. U.S.A.LEVINE S.B. U.S.A. MCCABE M. AustraliaOSWALDO R. Brazil PLAUT M. U.S.A.WYLIE K. U.K. 3. Educational, Socio-Cultural and Ethical

Aspects of Sexual Dysfunctions BONDIL P. FranceDABEES K. EgyptDEAN J. U.K.FOURCROY J. U.S.A.GINGELL C. U.K. KINGSBERG S. U.S.A. KOTHARI P. IndiaOKUYAMA A. JapanRUBIO AURIOLES E. MexicoUGARTE F. MexicoVELA NAVARRETE R. SpainWAGNER G. Denmark 4. Economical Aspects of Sexual DysfunctionsAMAR E. FranceHACKETT G. U.K. JAROW J. U.S.A.KIMOTO Y. JapanMIRONE V. ItalyRICHTER S. Israël SCHMIDT A. S.AfricaSHABSIGH R. U.S.A.YAFFE L. U.S.A. 5. Clinical Evaluation and Symptom Scores of

Sexual Dysfunctions BRODERICK G. U.S.A.CLAYTON A. U.S.A.CUZIN B. France DEROGATIS L. U.S.A.HATZICHRISTOU D. Greece LITWIN M. U.S.AMEULEMAN E. The Netherlands

O’LEARY M. U.S.A. POPAY J. U.K. QUIRK F. U.K. ROSEN R. U.S.A.SADOVSKY R. U.S.A.SEFTEL A. U.S.A. 6. Standards for Clinical Trials in Sexual

Dysfunctions : Research Designs and Outcomes Assessment

DONATUCCI C. U.S.A.GLINA S. BrazilGUESS M. U.S.A.HEIMAN J. U.S.A. HIRSCH M. U.S.A. HYDE J.S. U.S.A.MONTAGUE K. U.S.A.MONTORSI F. ItalySEGRAVES R.T. U.S.A.WYLLIE M. U.K. 7. Physiology - Pathophysiology of Female

Sexual Function GIRALDI A. Denmark GOLDSTEIN I. U.S.A.KADIOGLU A. TurkeyMARSON L. U.S.A.NAPPI R. ItalyPFAUS J. CanadaSALONIA A. Italy TRAISH A. U.S.AVAN LUNSEN R. The NetherlandsVARDI Y Israel 8. Priapism, Peyronie’s Disease and Penile

Reconstructive Surgery AKKUS E. TurkeyALTER G. U.S.A.JORDAN G.H. U.S.A. LEBRET T. France LEVINE L.A. U.S.A.MULHALL J. U.S.A.PEROVIC S. SerbiaPRYOR J. U.K.RALPH D. U.K.STACKL W. Austria 9. Disorders of Orgasm in Male and Female,

Ejaculatory Disorders in Males ABDO C. BrazilHULL E. U.S.A.INCROCCI L. The NetherlandsLEVIN R. U.K.MCMAHON C. Australia MESTON C. U.S.A.PERELMAN M. U.S.A.ROWLAND D. U.S.A. WALDINGER M.D. The NetherlandsXIN Z.C China

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MEMBERS OF THE COMMITTEES (by Committee)

10. Experimental Studies of Sexual Functions and Dysfunctions IncludingBrain Imaging Studies

ADAMS M Canada BAUM M. U.S.A.BIVALACQUA T. U.S.A. HEDLUND P. SwedenMC KENNA K. U.S.A.PARK K. KoreaPESCATORI E. ITALYRAJFER J. U.S.A.SATO Y. Japan 11. Physiology, Molecular Biology of Erectile

Function and Pathophysiology of ErectileDysfunction

ANGULO J. SpainCELLEK S. U.K.GONZALES-CADAVID N. U.S.A.HEATON J. CanadaPICKARD R. U.K.SAENZ DE TEJADA I. SpainSIMONSEN U. Denmark 12. Endocrine Aspects of Male and Female

Sexual Dysfunctions including HormonalTreatment

SIMON A. U.S.A. BUVAT J. France DAVIS S. AustraliaGOH V. Singapore GOOREN L.J. The NetherlandsGUAY A. U.S.A. KAUFMAN J.M. Belgium KIM Y.C. Korea LEJEUNE H. France MAZER N. A. U.S.A.MORALES A. Canada SHIFREN J.L. U.S.A.TAN H.M. MalaysiaTORRES L.O. Brazil 13. Implants and Vascular Surgery, Mecha-

nical Devices for Erectile Dysfunction.AUSTONI E. ItalyBARADA J. U.S.A.CHOI H.C Korea HELLSTROM W. U.S.A. KRISNAMURTI S. India MONCADA I. SpainMULCAHY J. U.S.A. SCHULTHEISS D. Germany SOHN M. Germany WESSELLS H. U.S.A.

14. Pharmacological Treatment of Erectile Dysfunction

ADAIKAN G. SingaporeBECHER E. Argentina

BROCK G Canada CARRIER S. Canada CARSON C. U.S.A. CHRIST G. U.S.A. CORBIN J.D. U.S.A. EARDLEY I. U.K. HEDLUND H. Norway HUTTER D. U.S.A. JACKSON G. U.K. JÜNEMANN K.P Germany LIN C-S U.S.A.MC VARY K.T. U.S.A.MCCULLOUGH A. U.S.A. NEHRA A. U.S.A.PADMA-NATHAN H. U.S.A. PORST H. GermanySCHULMAN C.C. BelgiumSHARLIP I. U.S.A. STIEF C.G. GermanyTELOKEN C Brazil 15 Future Treatment Target ANDERSSON K.E. SwedenARGIOLAS A. Italy BURNETT A. U.S.A. CHEN K. China MILLS T.M. U.S.A. 16. Female Sexual Desire and Arousal

Disorders and Sexual Pain Disorders :Pathophysiology and Treatment

16 ALTHOF S. U.S.A. BASSON R. Canada BAUMEISTER R. U.S.A. BINIK I. CanadaBROTTO L. U.S.A.ESCHENBACH D. U.S.A. LAAN E. The NetherlandsLEIBLUM S. U.S.A. REDMOND G. U.S.A.SCHULTZ W.C. The NetherlandsUTIAN W. USAVAN LANKVELD J. The netherlandsWESSELMANN U. U.S.A. WYATT G. U.S.A. WYATT L. U.S.A. BANCROFT J. U.S.A. 17. Special Working Group on : “Qualitative

Methods in Sexuality Research” GIAMI A. France GRAHAM C. CanadaPOPAY J. U.K. ROSEN R. USASANDERS S. USATIEFER L. USA

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Prof. Robert KRANE Honorary President of the 2nd InternationalConsultation on Sexual Dysfunctions

Robert J. Krane, my mentor, my professor, my chairman, my friend. You left us too young. Howdo I describe you to people who never knew you? To put it simply, Bob Krane was a visionary.At a time when the word "sex" wasn't used publicly by anyone over 30, and no one would darecomplain of impotence, Bob had the vision to see that erectile dysfunction was a real problemwhich affected men deeply, and deserved medical attention. He took it upon himself to learnmore, and brought what we now know as sexual medicine to Northeastern United States.

I met Bob when I started as a resident at Boston University School of Medicine. At that time CarlOlsson was chair of the department. When Carl left for Columbia, Bob was a natural to take overthe department. At that time he became the youngest chairman of Urology in the U.S.

Right from the beginning Bob had a sense that the practice of the future was one of specializa-tion. His right hand man was Mike Siroky, who specialized in neurology. Bob had flown to Texasto learn from Brantley Scott himself how to implant this newfangled device, the penile prosthe-sis. I had always been interested in flow, but Bob turned to me one day and declared, I was tobecome the world's expert in penile vascular function. I had no idea to what he was referring, butI said yes.

Bob raised the funds to fly in Vaclav Michal, the developer of the penile microvacscular arterialbypass procedure, from Czechoslovakia. Vaclav showed me his technique in Boston and I trai-ned with one of our local vascular surgeons after he left. Thus started our first clinic for sexualdysfunction in 1978, although we couldn't call it that. It was named the New England MaleReproductive Center, avoiding the words sex or erectile dysfunction, but we no longer were res-tricted to just sex therapy to treat out patients. We added into the mix penile implants and peni-le revascularization surgery.

During that time we found funding sources to open a basic science lab, with Inigo Saenz de Teja-da as director. Bob knew that an academic practice needed hard science to back it up. In 1988 inBoston we co-chaired the International Society for Impotence Research, as the ISSIR was knownthen. By then Bob had friends around the world and was known as a brilliant physician and witty,thoughtful friend. Many of the world's most renown scientists in the field of impotence wereBob's personal friends, and attended this meeting.

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Over the years we learned the various therapies to treat erectile dysfunction. At the same timeour basic science researchers under the directorship of Abdul Traish and Noel Kim discovered therole of nitric oxide in smooth muscle relaxation facilitating erection. Bob Krane encouragedresearch and looking beyond the obvious. Over the years we had fellows from around the worldvisit us or train with us. In Bob's absence we continue with this model.

Everywhere we travel we find friends of Bob and Bambi's.

Bob's gift to us was this vision of which I spoke. The ordinary needed embellishment, the ave-rage needed education, the picture needed to extend into the future. This image of Bob helps toexplain his extraordinary ability to bring out the best in people. It also helps to explain his dri-ving passion that helped bring the field of sexual medicine to where it is today.

After helping to found the ISIR and chairing the 1988 meeting, Bob went on to be president for4 years ED consultation.

This year marks the 25th anniversary of the clinic started so long ago by Bob Krane to treat impo-tence, then erectile dysfunction and now sexual medicine. Along the way he trained scores ofresidents, many fellows and hundreds of health care professionals as he traveled the world. It isfitting that we remember him to today at the this consultation on sexual dysfunctions.

This is the legacy Bob leaves us. Never settle for what is, when we can learn so much more. Askquestions. Talk to people. Make friends. In the world Bob was born into talking about sex wastaboo. Now we proclaim to the world that every human being has a right to health includingsexual health.

Bob's special legacy to me was his allowing me to follow my passion. Today this gift continuesto live as I am attempting to follow that vision and create a department of sexual medicine. Buteverywhere I look I see and hear Bob--in his family's faces, in his friends' conversations, in hisformer students' research and in myself whenever I have a new idea.

You left us too young, but thank you Bob for all you have left for us to do, and thank you for thegiving us the passion with which to do it. We shall follow in your footsteps and leave carry itthrough to the next generation.

Irwin Goldstein

CHAPTER 1 Historical Highlights of Erectile and Sexual Dysfunction An Illustrated Chronology - DIRK SCHULTHEISS (GERMANY) 19

CHAPTER 2 Committee 1 Definitions, Classification, and Epidemiology of Sexual Dysfunction 37

R. W. LEWIS (USA), K.S. FUGL-MEYER (SWEDEN), R. BOSCH (NETHERLANDS), A. R. FUGL-MEYER (SWEDEN),E. O. LAUMANN (USA), E. LIZZA (USA), A. MARTIN-MORALES (SPAIN)

CHAPTER 3 Committee 2 Psychological and Interpersonal Dimensions of Sexual Function and Dysfunction 73

S.E. ALTHOF (USA), S.R. LEIBLUM (USA), M. CHEVERT-MEASSON (FRANCE), U. HARTMAN (GERMANY), S.B. LEVINE (USA), M. MCCABE (AUSTRALIA),M. PLAUT (USA),O. RODRIGUES (BRAZIL), K. WYLIE (U.K)

CHAPTER 4 Committee 3 Ethical, Socio-cultural and Educational Aspects of Sexual Medicine 117

G. WAGNER (DENMARK) P. BONDIL (FRANCE), K. DABEES (EGYPT), J. DEAN (U.K), J. FOURCROY (USA), C. GINGELL (U.K), S. KINGSBERG (USA), P. KOTHARI (INDIA), E. RUBIO AURIOLES (MEXICO), F. UGARTE (MEXICO), R. VELA NAVARRETE (SPAIN)

CHAPTER 5 Committee 4 Economical Aspects of Sexual Dysfunctions 139R. SHABSIGH (USA), Y. KIMOTO (JAPAN), E. AMAR (FRANCE), G. HACKETT (U.K), J.P. JAROW (USA), V. MIRONE (ITALY), S. RICHTER (ISRAEL), A. SCHMIDT (S. AFICA), L. YAFFE (USA)

CHAPTER 6 Committee 17 Qualitative Health Research and Sexual Dysfunction 161L. TIEFER (USA), R. ROSEN (USA) A. GIAMI (FRANCE), J. POPAY (U.K.), C. GRAHAM (USA), S. SANDERS (USA)

CHAPTER 7 Committee 5 Clinical Evaluation and Symptom Scales: Sexual Dysfunction Assessment in Men 173

R. ROSEN (U.S.A.), D. HATZICHRISTOU (GREECE), G. BRODERICK (USA), A. CLAYTON (USA), B. CUZIN (FRANCE), L. DEROGATIS (USA), M. LITWIN (USA), E. MEULEMAN (THE NETHERLANDS), M. O’LEARY (USA), F. QUIRK (UK), R. SADOVSKY (USA), A. SEFTEL (USA) Assistant M. WIEGEL (USA)

CHAPTER 8 Committee 6 A Standards for Clinical Trials in Male Sexual Dysfunction:Erectile Dysfunction and Rapid Ejaculation 221

M. HIRSCH (USA), C. DONATUCCI (USA), S. GLINA (BRAZIL), D. MONTAGUE (USA), F. MONTORSI (ITALY), M. WYLLIE (U.K)

CHAPTER 9 Committee 10 Experimental Models for the Study of Male Sexual Function 241

K. MCKENNA (USA), M.A. ADAM (USA), T. BIVALACQUA (USA), L. COOLEN (USA), N. GONZALEZ-CADAVID (USA), P. HEDLUND (SWEDEN), K. PARK (KOREA), E. PESCATORI (ITALY), J.RAJFER (USA), Y. SATO (JAPAN)

CHAPTER 10 Committee 11 Physiology of Erectile Function and Pathophysiology of Erectile Dysfunction 287

I. SÁENZ DE TEJADA (SPAIN), J. ANGULO (SPAIN), S. CELLEK (U.K), N.F. GONZÁLEZ-CADAVID (USA), J. HEATON (CANADA), R. PICKARD (U.K), U. SIMONSEN (DENMARK)

SEXUAL DYSFUNCTIONS IN MEN2

BASIC CONSIDERATIONS1

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CONTENTS

CHAPTER 11 Committee 12A Endocrine Aspects of Men Sexual Dysfunction 345 A. MORALES (CANADA), J. BUVAT (FRANCE), L.J. GOOREN (NETHERANDS), A.T. GUAY (USA), J.M. KAUFMAN (BELGIUM), YOUNG C. KIM (KOREA), H.M. TAN (MALAYSIA), L.O. TORRES (BRAZIL)

CHAPTER 12 Committee 8 Priapism, Peyronie’s Disease, Penile Reconstructive Surgery 383

J. PRYOR (U.K), E. AKKUS (TURKEY), G. ALTER (USA), G. JORDAN (USA), T. LEBRET (FRANCE), L. LEVINE (USA), J. MULHALL (USA), S. PEROVIC (SERBIA), D. RALPH (U.K.), W. STACKL (AUSTRIA)

CHAPTER 13 Committee 9 A Disorders of Orgasm and Ejaculation in Men 409C. G MCMAHON (AUSTRALIA), C. ABDO (BRAZIL), E. HULL (USA), L. INCROCCI (NETHERLANDS), R. LEVIN (U.K), M. PERELMAN (USA), D. ROWLAND (USA), M. SIPSKI (USA), B. STUCKEY (AUSTRALIA), M. WALDINGER (THE NETHERLANDS) Z. CHENG XIN (CHINA)

CHAPTER 14 Committee 13 Implants, Mechanical Devices and Vascular Surgery for Erectile Dysfunction 469

JOHN J. MULCAHY (USA), E. AUSTONI (ITALY), J. H. BARADA (USA), H. KI CHOI (KOREA), W. J.G. HELLSTROM (USA), S. KRISNAMURTI (INDIA), I. MONCADA (SPAIN), D. SHULTHEISS (GERMANY), M. SOHN (GERMANY), H. WESSELLS (USA)

CHAPTER 15 Committee 14 Pharmacotherapy for Erectile Dysfunction 503H. PADMA-NATHAN (USA), G.CHRIST (USA), G.ADAIKAN (SINGAPORE), E. BECHER (ARGENTINA), G. BROCK (CANADA), S. CARRIER (CANADA), C. CARSON (USA), J. CORBIN (USA), S. FRANCIS (USA), R. DEBUSK (USA), I. EARDLEY (U.K.), H. HEDLUND (NORWAY), A. HUTTER (USA), G. JACKSON (U.K.), R. KLONER (USA), C. LIN (USA), K. MCVARY (USA), A. MCCULLOUGH (USA), A. NEHRA (USA), H. PORST (GERMANY), C. SCHULMAN (BELGIUM), A. SEFTEL (USA), I. SHARLIP (USA), C. STIEF (GERMANY), C. TELOKEN (BRAZIL)

CHAPTER 16 Committee 15 Future Treatment Targets 567K-E ANDERSSON (SWEDEN), A. ARGIOLAS (ITALY), A. BURNETT (USA), K.K CHEN (CHINA), T.M MILLS (USA), W. D STEERS (USA)

CHAPTER 17 SUMMARY OF THE RECOMMENDATION FOR MEN 605

CHAPTER 18 Committee 6B Standards for Clinical Trials in Sexual Dysfunctions of Women: Research Designs and Outcomes Assessment 631J. R. HEIMAN (USA), M. K. GUESS (USA), K. CONNELL (USA), A. MELMAN (USA),J. S. HYDE (USA), T. SEGRAVES (USA), M. G. WYLLIE (U.K)

CHAPTER 19 Committee 7 Physiology of Female Sexual Function and Pathophysiology of Female Sexual Dysfunction 683

I. GOLDSTEIN (USA), A. GIRALDI (DENMARK), A. KODIGLIU (TURKEY),HW VAN LUNSEN (THE NETHERLANDS), L. MARSON (USA), R. NAPPI (ITALY),J. PFAUS (CANADA), A. SALONIA (ITALY), A.M. TRAISH (USA), Y. VARDI (ISRAEL)

CHAPTER 20 Committee 12B Endocrine Aspects of Female Sexual Dysfunction 749S.R. DAVIS (AUSTRALIA), A.T. GUAY (USA), J.L. SHIFREN (USA), N.A. MAZER (USA)

CHAPTER 21 Committee 9B Women’s Orgasm 783C.M. MESTON (USA), E. HULL (USA), R.J. LEVIN (UK), M. SIPSKI (USA)

CHAPTER 22 Committee 16 Women’s Sexual Desire and Arousal Disorders and Sexual Pain 851

R. BASSON (CANADA), W.C.M. WEIJMAR SHULTZ (NETHERLANDS) Y.M. BINIK (CANADA), L.A. BROTTO (USA), D.A. ESCHENBACH (USA), E. LAAN (NETHERLANDS), W.H. UTIAN (USA),U. WESSELMANN (USA), J. VAN LANKVELD (NETHERLANDS), G. WYATT (USA), L. WYATT (USA),S. LEIBLUM (USA), S.E. ALTHOF (USA), G. Redmond (USA)

CHAPTER 23 SUMMARY OF THE RECOMMENDATION FOR WOMEN 975

SEXUAL DYSFUNCTIONS IN WOMEN3

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INTRODUCTION

The International Consultation on Urological Diseases (ICUD)is a non-governmental organization registered with the WorldHealth Organisation (WHO). In the last ten years Consultationshave been organised on BPH, Prostate Cancer, Urinary StoneDisease, Nosocomial Infections, Erectile Dysfunction and Uri-nary Incontinence. These consultations have looked at publi-shed evidence and produced recommendations at four levels;highly recommended, recommended, optional and not recom-mended. This method has been useful but the ICUD believesthat there should be more explicit statements of the levels ofevidence that generate the subsequent grades of recommen-dations.

The Agency for Health Care Policy and Research (AHCPR)have used specified evidence levels to justify recommenda-tions for the investigation and treatment of a variety of condi-tions. The Oxford Centre for Evidence Based Medicine haveproduced a widely accepted adaptation of the work of AHCPR.(June 5th 2001 http://minerva.minervation .com/cebm/docs/levels.html).

The ICUD has examined the Oxford guidelines and discussedwith the Oxford group their applicability to the Consultationsorganised by ICUD. It is highly desirable that the recommen-dations made by the Consultations follow an accepted gradingsystem supported by explicit levels of evidence.

The ICUD proposes that future consultations should use amodified version of the Oxford system which can be directly‘mapped’ onto the Oxford system.

1. 1st Step: Define the specific questions or statementsthat the recommendations are supposed to address.

2. 2nd Step: Analyse and rate (level of evidence) the rele-vant papers published in the literature.

The analysis of the literature is an important step in prepa-ring recommendations and their guarantee of quality.

2.1 What papers should be included in the analysis ?

• Papers published, or accepted for publication in the peerreviewed issues of journals.

• The committee should do its best to search for papersaccepted for publication by the peer reviewed journals in therelevant field but not yet published.

• Abstracts published in peer review journals should be iden-tified. If of sufficient interest the author(s) should be askedfor full details of methodology and results. The relevantcommittee members can then ‘peer review’ the data, and ifthe data confirms the details in the abstract, then that abs-tract may be included, with an explanatory footnote. This isa complex issue – it may actually increase publication biasas “uninteresting” abstracts commonly do not progress tofull publication.

• Papers published in non peer reviewed supplements will notbe included.

An exhaustive list should be obtained through:

I. the major databases covering the last ten years (e.g. Med-line, Embase, Cochrane Library, Biosis, Science CitationIndex)

II. the table of contents of the major journals of urology andother relevant journals, for the last three months, to take intoaccount the possible delay in the indexation of the publi-shed papers in the databases.

It is expected that the highly experienced and expert commit-

tee members provide additional assurance that no importantstudy would be missed using this review process.

2.2 How papers are analysed ?

Papers published in peer reviewed journals have differing qua-lity and level of evidence.

Each committee will rate the included papers according tolevels of evidence (see below).

The level (strength) of evidence provided by an individual studydepends on the ability of the study design to minimise the pos-sibility of bias and to maximise attribution.

is influenced by:

• the type of study

The hierarchy of study types are:

- Systematic reviews and meta-analysis of randomisedcontrolled trials

- Randomised controlled trials

- Non-randomised cohort studies

- Case control studies

- Case series

- Expert opinion

• how well the study was designed and carried out

Failure to give due attention to key aspects of study methodo-logy increase the risk of bias or confounding factors, and thusreduces the study’s reliability.

The use of standard check lists is recommended to insurethat all relevant aspects are considered and that a consistentapproach is used in the methodological assessment of the evi-dence.

The objective of the check list is to give a quality rating for indi-vidual studies.

• how well the study was reported

The ICUD has adopted the CONSORT statement and its wide-ly accepted check list. The CONSORT statement and thechecklist are available at http: //www.consort-statement.org

2.3 How papers are rated ?

Papers are rated following a « Level of Evidence scale ».

ICUD has modified the Oxford Center for Evidence-BasedMedicine levels of evidence.

The levels of evidence scales vary between types of studies (ietherapy, diagnosis, differential diagnosis/symptom prevalencestudy).

the Oxford Center for Evidence-Based Medicine Website:http://minerva. minervation. com/cebm /docs/ levels. html

3. 3rd Step: Synthesis of the evidence

After the selection of the papers and the rating of the level ofevidence of each study, the next step is to compile a summaryof the individual studies and the overall direction of the eviden-ce in an Evidence Table.

4. 4th Step: Considered judgment (integration of indivi-dual clinical expertise)

Having completed a rigorous and objective synthesis of the evi-dence base, the committee must then make a judgement as tothe grade of the recommendation on the basis of this evidence.This requires the exercise of judgement based on clinical expe-rience as well as knowledge of the evidence and the methods

EVIDENCE – BASED MEDICINE OVERVIEW OF THE MAIN STEPS FOR DEVELOPING AND GRADING GUIDELINE RECOMMENDATIONS.

used to generate it. Evidence based medicine requires the inte-gration of individual clinical expertise with best available exter-nal clinical evidence from systematic research. Without the for-mer, practice quickly becomes tyrannised by evidence, foreven excellent external evidence may be inapplicable to, orinappropriate for, an individual patient: without current best evi-dence, practice quickly becomes out of date. Although it is notpractical to lay our “rules” for exercising judgement, guidelinedevelopment groups are asked to consider the evidence interms of quantity, quality, and consistency; applicability; gene-ralisability; and clinical impact.

5. 5th Step: Final Grading

The grading of the recommendation is intended to strike anappropriate balance between incorporating the complexity oftype and quality of the evidence and maintaining clarity for gui-deline users.

The recommendations for grading follow the Oxford Centre forEvidence-Based Medicine.

The levels of evidence shown below have again been modifiedin the light of previous consultations. There are now 4 levels ofevidence instead of 5.

The grades of recommendation have not been reduced and a“no recommendation possible” grade has been added.

6. Levels of Evidence and Grades of RecommendationTherapeutic Interventions

All interventions should be judged by the body of evidence fortheir efficacy, tolerability, safety, clinical effectiveness and costeffectiveness. It is accepted that at present little data exists oncost effectiveness for most interventions.

6.1 Levels of Evidence

Firstly, it should be stated that any level of evidence may bepositive (the therapy works) or negative (the therapy doesn’twork). A level of evidence is given to each individual study.

• Level 1 evidence (incorporates Oxford 1a, 1b) usuallyinvolves meta-anaylsis of trials (RCTs) or a good qualityrandomised controlled trial, or ‘all or none’ studies in whichno treatment is not an option, for example in vesicovaginalfistula.

• Level 2 evidence (incorporates Oxford 2a, 2b and 2c)includes “low” quality RCT (e.g. < 80% follow up) or meta-analysis (with homogeneity) of good quality prospective‘cohort studies’. These may include a single group whenindividuals who develop the condition are compared withothers from within the original cohort group. There can beparallel cohorts, where those with the condition in the firstgroup are compared with those in the second group.

• Level 3 evidence (incorporates Oxford 3a, 3b and 4)includes:

good quality retrospective ‘case-control studies’ where a groupof patients who have a condition are matched appropriately(e.g. for age, sex etc) with control individuals who do not havethe condition.

good quality ‘case series’ where a complete group of patientsall, with the same condition/disease/therapeutic intervention,are described, without a comparison control group.

• Level 4 evidence (incorporates Oxford 4) includes expertopinion were the pinion is based not on evidence but on‘first principles’ (e.g. physiological or anatomical) or benchresearch. The Delphi process can be used to give ‘expertopinion’ greater authority. In the Delphi process a series ofquestions are posed to a panel; the answers are collectedinto a series of ‘options’; the options are serially ranked; ifa 75% agreement is reached then a Delphi consensus sta-tement can be made.

6.2 Grades of Recommendation

The ICUD will use the four grades from the Oxford system. Aswith levels of evidence the grades of evidence may apply eitherpositively (do the procedure) or negatively (don’t do the proce-dure). Where there is disparity of evidence, for example if therewere three well conducted RCT’s indicating that Drug A wassuperior to placebo, but one RCT whose results show no diffe-rence, then there has to be an individual judgement as to thegrade of recommendation given and the rationale explained.

• Grade A recommendation usually depends on consistentlevel 1 evidence and often means that the recommendationis effectively mandatory and placed within a clinical carepathway. However, there will be occasions where excellentevidence (level 1) does not lead to a Grade A recommen-dation, for example, if the therapy is prohibitively expensive,dangerous or unethical. Grade A recommendation can fol-low from Level 2 evidence. However, a Grade A recom-mendation needs a greater body of evidence if based onanything except Level 1 evidence

• Grade B recommendation usually depends on consistentlevel 2 and or 3 studies, or ‘majority evidence’ from RCT’s.

• Grade C recommendation usually depends on level 4 stu-dies or ‘majority evidence’ from level 2/3 studies or Dephiprocessed expert opinion. Grade C recommendation isgiven when expert opinion is delivered without a formal ana-lytical process, such as by Dephi.

• Grade D “No recommendation possible” would be usedwhere the evidence is inadequate or conflicting.

7. Levels of Evidence and Grades of Recommendationfor Methods of Assessment and Investigation

From initial discussions with the Oxford group it is clear thatapplication of levels of evidence/grades of recommendation fordiagnostic techniques is much more complex than for interven-tions. The ICUD recommend, that, as a minimum, any testshould be subjected to three questions:

1. does the test have good technical performance, for example,do three aliquots of the same urine sample give the sameresult when subjected to ‘stix’ testing?

2. Does the test have good diagnostic performance, ideallyagainst a “gold standard” measure?

3. Does the test have good therapeutic performance, that is,does the use of the test alter clinical management, does theuse of the test improve outcome?

For the third component (therapeutic performance) the sameapproach can be used as for section 6.

8. Levels of Evidence and Grades of Recommendation forBasic Science and Epidemiology Studies

The proposed ICUD system does not easily fit into these areasof science. Further research needs to be carried out, in orderto develop explicit levels of evidence that can lead to recom-mendations as to the soundness of data in these importantaspects of medicine.

CONCLUSION

The ICUD believes that its consultations should follow theICUD system of levels of evidence and grades of recom-mendation, where possible. This system can be mappedto the Oxford system.

There are aspects to the ICUD system that require furtherresearch and development, particularly diagnostic perfor-mance and cost effectiveness, and also factors such aspatient preference.

P. Abrams, S Khoury, A. Grant 19/1/04

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CHAPTER 1 Historical Highlights of Erectile and Sexual Dysfunction An Illustrated Chronology - DIRK SCHULTHEISS (GERMANY)

CHAPTER 2 Committee 1 Definitions, Classification, and Epidemiology of Sexual Dysfunction

R. W. LEWIS (USA), K.S. FUGL-MEYER (SWEDEN), R. BOSCH (NETHERLANDS), A. R. FUGL-MEYER (SWEDEN),E. O. LAUMANN (USA), E. LIZZA (USA), A. MARTIN-MORALES (SPAIN)

CHAPTER 3 Committee 2 Psychological and Interpersonal Dimensions of Sexual Function and Dysfunction

S.E. ALTHOF (USA), S.R. LEIBLUM (USA), M. CHEVERT-MEASSON (FRANCE), U. HARTMAN (GERMANY), S.B. LEVINE (USA), M. MCCABE (AUSTRALIA),M. PLAUT (USA),O. RODRIGUES (BRAZIL), K. WYLIE (U.K)

CHAPTER 4 Committee 3 Ethical, Socio-cultural and Educational Aspects of Sexual Medicine

G. WAGNER (DENMARK) P. BONDIL (FRANCE), K. DABEES (EGYPT), J. DEAN (U.K), J. FOURCROY (USA), C. GINGELL (U.K), S. KINGSBERG (USA), P. KOTHARI (INDIA), E. RUBIO AURIOLES (MEXICO), F. UGARTE (MEXICO), R. VELA NAVARRETE (SPAIN)

CHAPTER 5 Committee 4 Economical Aspects of Sexual DysfunctionsR. SHABSIGH (USA), Y. KIMOTO (JAPAN), E. AMAR (FRANCE), G. HACKETT (U.K), J.P. JAROW (USA), V. MIRONE (ITALY), S. RICHTER (ISRAEL), A. SCHMIDT (S. AFICA), L. YAFFE (USA)

CHAPTER 6 Committee 17 Qualitative Health Research and Sexual Dysfunction

L. TIEFER (USA), R. ROSEN (USA.) A. GIAMI (FRANCE), J. POPAY (U.K.), C. GRAHAM (USA), S. SANDERS (USA)

BASIC CONSIDERATIONS

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