A NDROGEN E XCESS D ISORDERSIN W OMEN

A ^NDROGEN E ^XCESS D ISORDERS IN W ^OMEN

C ONTEMPORARY E NDOCRINOLOGY

P. Michael Conn, S ^ERIES E ^DITOR

Treatment of the Obese Patient, edited by R

F. K

D

H. B

, 2007 Androgen Excess Disorders in Women: Polycystic

Ovary Syndrome and Other Disorders, Second Edition, edited by R

A

, J

E. N

,

D

D

, 2006

Evidence-Based Endocrinology, edited by V

M. M

, 2006

Stem Cells in Endocrinology, edited by L

B.

L

, 2005

Office Andrology, edited by P

E. P

D

E. B

, 2005

Male Hypogonadism: Basic, Clinical, and Therapeutic Principles, edited by S

J. W

, 2004

Androgens in Health and Disease, edited by C

B

W

J. B

, 2003

Endocrine Replacement Therapy in Clinical Practice, edited by A. W

M

, 2003 Early Diagnosis of Endocrine Diseases, edited

by R

S. B

, 2003

Type I Diabetes: Etiology and Treatment, edited by M

A. S

, 2003

Handbook of Diagnostic Endocrinology, edited by J

E. H

L

K. N

, 2003

Pediatric Endocrinology: A Practical Clinical Guide, edited by S

R

M

H. M

G

, 2003 Diseases of the Thyroid, 2nd ed., edited by

L

E. B

, 2003

Developmental Endocrinology: From Research to Clinical Practice, edited by E

A.

E

O

H

P

, 2002 Osteoporosis: Pathophysiology and Clinical

Management, edited by E

S. O

M

B

, 2002

Challenging Cases in Endocrinology, edited by M

E. M

, 2002

Selective Estrogen Receptor Modulators:

Research and Clinical Applications, edited by A

M

M

F.

V

, 2002

Transgenics in Endocrinology, edited by M

M

, C

W. B

,

AND

T. R

K

, 2001

Assisted Fertilization and Nuclear Transfer in Mammals, edited by D

P. W

M

Z

-W

, 2001

Adrenal Disorders, edited by A

N. M

G

P. C

, 2001

Endocrine Oncology, edited by S

P. E

, 2000

Endocrinology of the Lung: Development and Surfactant Synthesis, edited by C

R. M

, 2000

Sports Endocrinology, edited by M

P.

W

N

W. C

, 2000 Gene Engineering in Endocrinology, edited by

M

A. S

, 2000 Endocrinology of Aging, edited by J

E.

M

L

B

, 2000 Human Growth Hormone: Research

and Clinical Practice, edited by R

G. S

M

O. T

, 2000

Hormones and the Heart in Health and Disease, edited by L

S

, 1999

Menopause: Endocrinology and Management, edited by D

B. S

AND

E

A. K

, 1999 The IGF System: Molecular Biology,

Physiology, and Clinical Applications, edited by R

G. R

AND

C

T. R

, J

., 1999 Neurosteroids: A New Regulatory Function

in the Nervous System, edited by E

-E

B

, M

S

,

AND

P

R

, 1999

Autoimmune Endocrinopathies, edited by R

V

, 1999

Hormone Resistance Syndromes, edited by J. L

J

, 1999

Hormone Replacement Therapy, edited by A. W

M

, 1999

Insulin Resistance: The Metabolic Syndrome X, edited by G

M. R

A

L

, 1999

Endocrinology of Breast Cancer, edited by A

M

, 1999

Molecular and Cellular Pediatric Endocrinology, edited by S

H

, 1999 Gastrointestinal Endocrinology, edited by

G

H. G

, J

., 1999

A ^NDROGEN E ^XCESS D ^ISORDERS

IN W ^OMEN

P ^OLYCYSTIC O ^VARY S ^YNDROME

AND O ^THER D ^ISORDERS S ^ECOND E ^DITION

Edited by

R ^ICARDO A ^ZZIZ , ^MD , ^MPH , ^MBA

Center for Androgen Related Disorders, Cedars-Sinai Medical Center;

and Department of Obstetrics and Gynecology, and Department of Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, CA

J ^OHN E. N ^ESTLER , ^MD

Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA

D ^IDIER D ^EWAILLY , ^MD

Department of Endocrine Gynaecology and Reproductive Medicine,

Lille University Hospital, Lille, France

© 2006 Humana Press Inc.

999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 humanapress.com

All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher.

All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher.

Due diligence has been taken by the publishers, editors, and authors of this book to assure the accuracy of the information published and to describe generally accepted practices. The contributors herein have carefully checked to ensure that the drug selections and dosages set forth in this text are accurate and in accord with the standards accepted at the time of publication. Notwithstanding, as new research, changes in government regulations, and knowledge from clinical experience relating to drug therapy and drug reactions constantly occurs, the reader is advised to check the product information provided by the manufacturer of each drug for any change in dosages or for additional warnings and contraindications. This is of utmost importance when the recommended drug herein is a new or infrequently used drug. It is the responsibility of the treating physician to determine dosages and treatment strategies for individual patients. Further it is the responsibility of the health care provider to ascertain the Food and Drug Administration status of each drug or device used in their clinical practice. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences from the application of the information presented in this book and make no warranty, express or implied, with respect to the contents in this publication.

This publication is printed on acid-free paper. f

ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials.

Production Editor: Robin B. Weisberg Cover design by Patricia F. Cleary

For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341; E-mail:

orders@humanapr.com; or visit our Website: www.humanapress.com Photocopy Authorization Policy:

Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients is granted by Humana Press, provided that the base fee of US $30.00 per copy is paid directly to the Copyright Clearance Center (CCC), 222 Rosewood Dr., Danvers MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to the Humana Press. The fee code for users of the Transactional Reporting Service is 1- 58829-663-6/06 $30.00.

Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 eISBN 1-59745-179-7

Library of Congress Cataloging-in-Publication Data

Androgen excess disorders in women : polycystic ovary syndrome and other disorders / edited by Ricardo Azziz, John E. Nestler, Didier Dewailly.-- 2nd ed.

p. ; cm. -- (Contemporary endocrinology) Includes bibliographical references and index.

ISBN 1-58829-663-6 (alk. paper)

1. Adrenal glands--Diseases. 2. Androgens--Metabolism. 3. Androgens--Physiological effect.

4. Polycystic ovary syndrome.

[DNLM: 1. Adrenocortical Hyperfunction. 2. Hyperandrogenism. 3. Androgens.

4. Polycystic Ovary Syndrome. WK 770 A573 2006] I. Azziz, Ricardo. II. Nestler, John E.

III. Dewailly, Didier. IV. Series: Contemporary endocrinology (Totowa, N.J.) RG207.5.A53 2006

618.1--dc22

2006003453

D ^EDICATION

v

To Cindy, Ashlee, Jonathon, and Mallory, for their loving and patient support and encouragement.

—RA

To my brother, Gregory, whose love, encouragement, and sense of humor were always a source of comfort.

—JEN To my family and friends, with love and fondness.

—DD

P ^REFACE

vii

The field of androgen excess disorders has advanced substantially since the original publication of this book. The Androgen Excess Society (AES) was founded to bring together investigators in the field. A better understanding of the screening, progression, and molecular genetics of nonclassic adrenal hyperplasia (NCAH) has improved the clinical care and diagnostic accuracy of these patients. New criteria for the diagnosis of the polycystic ovary syndrome (PCOS) were proposed in Rotterdam, criteria that have resulted in controversy and, hopefully, initiation of new studies. The association of insulin resistance with PCOS has been strengthened, and the role of metformin in treat- ing the infertility of the PCOS has been validated. Risks for diabetes and, more contro- versially, cardiovascular disease in women with PCOS have received substantial investigation. Our understanding of the epidemiology and economic impact of these disorders has expanded, emphasizing their critical importance. These are but a few highlights of how the terrain has changed in a relatively brief period of time.

In keeping with these advances, the title of this book has been revised to reflect the growing importance of PCOS as the most prevalent androgen excess disorder in women, and arguably, as the one that might have the most serious adverse consequences for general health. There are fewer chapters to provide a more focused elucidation of the area. Several chapters were penned by new (and young) authors who are conducting cutting-edge research in the field. The time line for publication of the book was inten- tionally kept tight, so that the information would be fresh and current. Although the editors have grown grayer, and not necessarily wiser, we nonetheless hope that this second edition of Androgen Excess Disorders in Women: Polycystic Ovary Syndrome and Other Disorders will prove to be a helpful guide and resource for all clinicians and researchers in the field of androgen excess.

Ricardo Azziz, ^MD , ^MPH , ^MBA

John E. Nestler, ^MD

Didier Dewailly, ^MD

A CKNOWLEDGMENTS

A text of this size and depth cannot be created by only a dedicated few and the authors must, out of fairness, acknowledge the support and assistance of many. We would like to thank our staff who helped in the preparation and formatting of the many drafts involved, particularly acknowledging the expert administrative assistance of Lois Dollar and April Moore. We also greatly appreciate the support, patience, and guidance offered to us by the editorial staff at Humana Press, notably Richard Lansing, Executive Director for Continuing Medical Education and New Project Development; Patrick Marton, Acquisitons Editor; and Robin B. Weisberg, Director of Editorial Services. Our young collaborators, and past and present fellows, deserve special thanks for their generous and enthusiastic intellectual contributions; a notable example is Dr. Daniela Jakubowicz who has played a significant role in furthering our understanding of the therapeutic value of metformin in the polycystic ovary syndrome. We are also deeply indebted to the many authors who gave freely of their time and effort, and who endured our frequent requests for revisions under a tight and unforgiving timeline. Finally, we acknowledge with profound gratitude our many patients who suffer from androgen excess disorders, and who trusted us to care for them, teaching us so much about these disorders and about living gracefully despite their disability.

Ricardo Azziz, ^MD , ^MPH , ^MBA John E. Nestler, ^MD Didier Dewailly, MD

ix

C ^ONTENTS

xi

Dedication ...

Preface ...

Acknowledgments ...

Contributors ...

I. Introduction 1 A Brief History of Androgen Excess

Ricardo Azziz ... 3 II. Physiology of Androgens

2 Ovarian and Adrenal Androgen Biosynthesis and Metabolism Walter L. Miller, David H. Geller, and Mitchell Rosen ... 19 3 Androgens Throughout the Life of Women

C. Richard Parker, Jr. ... 35 4 Physiological Effects of Androgens in Women

T. Keta Hodgson and Glenn D. Braunstein ... 49 5 Androgen Measurements: Methods, Interpretation,

and Limitations

Frank Z. Stanczyk ... 63 III. Uncommon Causes of Androgen Excess

6 Androgen-Secreting Adrenal and Ovarian Neoplasms

Michel Pugeat, Gérald Raverot, Ingrid Plotton, Aude Brac de la Perrière, Pascale Mirakian, Henri Déchaud,

Nicole Berger, and Jean Louis Peix ... 75 7 Cushing’s Syndrome, Acromegaly, and Androgen Excess

Anne-Céline Reyss and Didier Dewailly ... 85 8 The Nonclassic Adrenal Hyperplasias

Didier Dewailly and Ricardo Azziz ... 91 9 Pregnancy-Related Androgen Excess

Howard D. McClamrock ... 107 10 Drug-Induced Hyperandrogenism

Barbara Neraud and Didier Dewailly ... 121 11 Severe Insulin-Resistant Hyperandrogenic Syndromes

David E. Moller, Antonio Vidal-Puig, and Ricardo Azziz ... 129 12 Idiopathic Hirutism

Enrico Carmina ... 139

xii Contents IV. The Polycystic Ovary Syndrome

13 Definition and Epidemiology of the Polycystic Ovary Syndrome

Ricardo Azziz ... 145 14 Clinical Features of the Polycystic Ovary Syndrome

Walter Futterweit, Evanthia Diamanti-Kandarakis,

and Ricardo Azziz ... 155 15 Biochemical Features of the Polycystic Ovary Syndrome

Adam H. Balen ... 169 16 Ovarian Histology, Morphology, and Ultrasonography

in the Polycystic Ovary Syndrome

Sophie Jonard, Yann Robert, Yves Ardaens,

and Didier Dewailly ... 183 17 Hypothalamic–Pituitary–Gonadotrophic Dysfunction

in the Polycystic Ovary Syndrome

R. Jeffrey Chang and Rinku V. Mehta ... 195 18 Ovarian Steroidogenic Abnormalities in the Polycystic Ovary

Syndrome

Denis A. Magoffin ... 203 19 Hypothalamic–Pituitary–Adrenal Dysfunction

in the Polycystic Ovary Syndrome

Bulent O. Yildiz, Enrico Carmina, and Ricardo Azziz ... 213 20 The Genetic Basis of the Polycystic Ovary Syndrome

Mark O. Goodarzi ... 223 21 Pediatric Hyperandrogenism and the Polycystic Ovary

Syndrome in Adolescence

Kathleen M. Hoeger ... 235 22 Environmental Factors in the Polycystic Ovary Syndrome

Marie-France Hivert and Jean-Patrice Baillargeon ... 247 23 Animal Models and Fetal Programming of the Polycystic

Ovary Syndrome

David H. Abbott, Daniel A. Dumesic, Jon E. Levine,

Andrea Dunaif, and Vasantha Padmanabhan ... 259 24 Insulin Resistance and Hyperinsulinism in the Polycystic

Ovary Syndrome

Paulina A. Essah and John E. Nestler ... 273 25 The Endocrine Impact of Obesity and Body Habitus

in the Polycystic Ovary Syndrome

Renato Pasquali and Alessandra Gambineri ... 283 26 Molecular Mechanisms of Insulin Resistance

in the Polycystic Ovary Syndrome

Theodore P. Ciaraldi ... 293

27 Menstrual Dysfunction and Endometrial Neoplasia in the Polycystic Ovary Syndrome and Other Androgen Excess Disorders

Abdulkadir Wagley and Paul Hardiman ... 303 28 E-Cell Dysfunction, Glucose Intolerance, and Diabetes

in the Polycystic Ovary Syndrome

David A. Ehrmann ... 319 29 Hypertension and Cardiovascular and Lipoprotein

Abnormalities in the Polycystic Ovary Syndrome

Francesco Orio and Stefano Palomba ... 325 30 Reproductive and Obstetrical Consequences of the Polycystic

Ovary Syndrome

Mary C. Johnson and Richard S. Legro ... 333 31 Psychosocial and Quality-of-life Consequences of Androgen

Excess and the Polycystic Ovary Syndrome

Onno E. Janssen, Susanne Hahn, and Sigrid Elsenbruch ... 343 32 Overview of Long-Term Morbidity and Economic Cost

of the Polycystic Ovary Syndrome

Ricardo Azziz ... 353 V. Evaluation and Treatment of Androgen Excess

33 Clinical and Hormonal Evaluation of Androgen Excess

Ricardo Azziz ... 365 34 Ovarian Suppression and Treatment of Hirsutism

Paolo Moghetti ... 377 35 Polycystic Ovary Syndrome and Ovulation Induction

Bulent O. Yildiz and Ricardo Azziz ... 389 36 In Vitro Fertilization for the Polycystic Ovary Syndrome

Hanadi Ba-Akdah, Ezgi Demirtas, Hananel Holzer,

William Buckett, and Seang Lin Tan ... 405 37 Surgical Management of the Polycystic Ovary Syndrome

Adam H. Balen ... 415 38 Use of Insulin Sensitizers in the Polycystic Ovary Syndrome

Kai I. Cheang and John E. Nestler ... 421 39 Weight Reduction and Lifestyle Modification in the Treatment

of Androgen Excess

Manny Noakes, Lisa J. Moran, Grant D. Brinkworth,

and Robert J. Norman ... 435 Index ... 445

Contents xiii

C ONTRIBUTORS

xv

D AVID H. A BBOTT , P h D • National Primate Research Center and Department of Obstetrics and Gynecology, University of Wisconsin, Madison, WI

Y VES A RDAENS , MD • Department of Radiology, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

R ICARDO A ZZIZ , MD , MPH , MBA • Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center; Department of Obstetrics and Gynecology, and Department of Medicine, The David Geffen School of Medicine at University of California, Los Angeles, CA

H ANADI B A -A KDAH , MD • Department of Obstetrics and Gynecology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada

J EAN -P ATRICE B AILLARGEON , MD , MSC • Division of Endocrinology, Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada

A DAM H. B ALEN , MD • Department of Reproductive Medicine, The General Infirmary, Leeds, UK

N ICOLE B ERGER , MD • Laboratoire d Anatomie et de Cytologie pathologiqus, Hopital Lyon Sud, Pienne-Benite, France

A UDE B RAC DE LA P ERRIÉRE , MD • Fédération d Endocrinologie, Pole Est des Hopitaux de Lyon, Bron, France

G LENN D. B RAUNSTEIN , MD • Department of Medicine, Cedars-Sinai Medical Center, Department of Medicine, The David Geffen School of Medicine at University of California, Los Angeles, CA

G RANT D. B RINKWORTH , P h D • CSIRO Human Nutrition, Adelaide, Australia W ILLIAM B UCKETT , MD • Department of Obstetrics and Gynecology, McGill

University, Royal Victoria Hospital, Montreal, Quebec, Canada

E NRICO C ARMINA , MD • Department of Clinical Medicine, University of Palermo, Palermo, Italy

R. J EFFREY C HANG , MD • Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla, CA

K AI I. C HEANG , P harm D • Department of Pharmacy, Virginia Commonwealth University School of Pharmacy, Richmond, VA

T HEODORE P. C IARALDI , P h D • Department of Medicine, University of California, San Diego, VA San Diego Healthcare System, San Diego, CA

H ENRI D ÉCHAUD , MD • Laboratoire de Radioanalyse, Pole Est des Hopitaux de Lyon, Hopital Neuro-Cardio, Lyon, France

E ZGI D EMIRTAS , MD • Department of Obstetrics and Gynecology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada

D IDIER D EWAILLEY , MD • Service d'Endocrinologie et Diabetologie, Department of Endocrine Gynaecology and Reproductive Medicine, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

E VANTHIA D IAMANTI -K ANDARAKIS , MD • Department of Medicine, Athens University

Medical School, Athens, Greece

xvi Contributors D ANIEL A. D UMESIC , MD • National Primate Research Center, University of Wiscon-

sin, Madison, WI and Reproductive Medicine & Infertility Associates, Woodbury, MN

A NDREA D UNAIF , MD • Division of Endocrinology, Metabolism and Molecular

Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL D AVID A. E HRMANN , MD • Section of Endocrinology, The University of Chicago,

Chicago, IL

S IGRID E LSENBRUCH , P h D • Institute of Medical Psychology, University Hospital of Essen Medical School, Essen, Germany

P AULINA A. E SSAH , MD • Division of Endocrinology and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA W ALTER F UTTERWEIT , MD , FACP • Division of Endocrinology, Mount Sinai School

of Medicine, New York, NY

A LESSANDRA G AMBINERI , MD • Department of Internal Medicine, S. Orsola-Malpighi, Bologna, Italy

D AVID H. G ELLER , MD , P h D • Ahmanson Department of Pediatrics Cedars-Sinai Medical Center; Department of Pediatrics, The David Geffen School of Medicine at UCLA, Los Angeles, CA

M ARK O. G OODZARZI , MD , P h D • Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center; Department of Medicine, The David Geffen School of Medicine at University of California, Los Angeles, CA

S USANNE H AHN , MD • Division of Endocrinology, Department of Medicine, University Hospital of Essen Medical School, Essen, Germany

P AUL H ARDIMAN , MBBS , MD , FRCOG • University Department of Obstetrics and

Gynaecology, Royal Free and University College of Medical School, London, UK M ARIE -F RANCE H IVERT , MD • Division of Endocrinology, Department of Internal

Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada

T. K ETA H ODGSON , BSN , RN • Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA

K ATHLEEN M. H OEGER , MD • Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY

H ANANEL H OLZER , MD • Department of Obstetrics and Gynecology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada

O NNO E. J ANSSEN , MD • Division of Endocrinology, Department of Medicine, University Hospital of Essen Medical School, Essen, Germany

M ARY C. J OHNSON , BS • Department of Obstetrics and Gynecology, Penn State College of Medicine, Penn State University College of Medicine, M.S. Hershey Medical Center, Hershey, PA

S OPHIE J ONARD , MD • Department of Endocrine Gynaecology and Reproductive Medicine, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

R ICHARD S. L EGRO , MD • Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA

J ON E. L EVINE , MD • Department of Neurobiology and Physiology, Northwestern University, Evanston, IL

D ENIS A. M AGOFFIN , P h D • Department of Obstetrics and Gynecology, Cedars-Sinai

Medical Center, Los Angeles, CA

H OWARD D. M C C LAMROCK , MD • Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD

R INKU V. M EHTA , MD • Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla, CA

W ALTER L. M ILLER , MD • Division of Endocrinology, UCSF Children's Hospital, Division of Endocrinology, Department of Pediatrics, University of California San Francisco, San Francisco, CA

P ASCALE M IRAKIAN , MD • Fédération d Endocrinologie, Pole Est des Hopitaux de Lyon, Bron, France

P AOLO M OGHETTI , MD • Division of Endocrinology and Metabolism, Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy

D AVID E. M OLLER , MD • Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ

L ISA J. M ORAN , BND • Research Center for Reproductive Health and CSIRO Human Nutrition, Adelaide, Australia

B ARBARA N ERAUD , MD • Service d'Endocrinologie et Diabetologie, Department of Endocrine Gynaecology and Reproductive Medicine, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

J OHN E. N ESTLER , MD • Division of Endocrinology and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA M ANNY N OAKES , P h D • Diet & Lifestyle Interventions, CSIRO Human Nutrition,

Adelaide, Australia

R OBERT J. N ORMAN , P h D • Department of Obstetrics and Gynecology, Research Centre for Reproductive Health, University of Adelaide, Adelaide, Australia

F RANCESCO O RIO , MD , P h D • Department of Molecular and Clinical Endocrinology and Oncology, University "Federico II," Naples, Italy

V ASANTHA P ADMANABHAN , MD • Departments of Pediatrics, Obstetrics and Gynecology, and Molecular and Integrative Physiology, University of Michigan Reproductive Sciences Program, Ann Arbor, MI

S TEFANO P ALOMBA , MD • Department of Obstetrics and Gynecology, University

"Magna Graecia” of Catanzaro, Catanzaro, Italy

C. R ICHARD P ARKER , J R ., P h D • Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL

R ENATO P ASQUALI , MD • Department of Internal Medicine, S. Orsola-Malpighi, Bologna, Italy

J EAN L OUIS P EIX , MD • Département de Chirurgie, Hopital Lyon Sud, Pienne-Benite, France

I NGRID P LOTTON , MD • Fédération d Endocrinologie, Pole Est des Hopitaux de Lyon, Bron, France

M ICHEL P UGEAT , MD • Fédération d Endocrinologie, Pole Est des Hopitaux de Lyon, Bron, France

G ÉRALD R AVEROT , MD • Fédération d Endocrinologie, Pole Est des Hopitaux de Lyon, Bron, France

A NNE -C ÉLINE R EYSS , MD • Department of Endocrine Gynaecology and Reproductive Medicine, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

Contributors xvii

Y ANN R OBERT , MD • Department of Radiology, Hopital Jeanne de Flandre, Centre Hospitalier et Universitaire de Lille, Lille, France

M ITCHELL R OSEN , MD • Division of Reproductive Endocrinology & Infertility,

Department of Obstetrics and Gynecology, UCSF Center for Reproductive Health, San Francisco, CA

F RANK Z. S TANCZYK , P h D • Departments of Obstetrics and Gynecology, University of Southern California, Keck School of Medicine, Women & Children's Hospital, Los Angeles, CA

S EANG L IN T AN , MBBS , FRCOG , FRCSC , MM ed ( O & G ) , MBA • Department of Obstetrics and Gynecology, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada

A NTONIO V IDAL -P UIG , MD , P h D • Metabolic Medicine, Addenbrooke’s Hospital, Cambridge, UK

A BDULKADIR W AGLEY , MB

h B , MRCOG • Department of Obstetrics and Gynecology, Royal Free & University College Medical School, London, UK

B ULENT O. Y ILDIZ , MD • Department of Medicine, Hacettepe University School of Medicine, and Department of Internal Medicine, Endocrinology & Metabolism Unit Hacettepe, Ankara, Turkey

xviii Contributors