Table Of ContentCONTEMPORARY ENDOCRINOLOGY™
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Business Media, LLC
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ALE YPOGONADISM
C E
ONTEMPORARY NDOCRINOLOGY
P. Michael Conn, S E
ERIES DITOR
Male Hypogonadism: Basic, Clinical, and Endocrinology of Aging, edited by JOHN E.
Therapeutic Principles,edited by MORLEYAND LUCRETIAVANDEN BERG, 2000
STEPHENJ. WINTERS,2004 Human Growth Hormone: Research and
Androgens in Health and Disease, edited by Clinical Practice, edited by ROY G. SMITH
CARRIE BAGATELLAND WILLIAMJ. BREMNER, AND MICHAEL O. THORNER,2000
2003 Hormones and the Heart in Health and Disease,
Endocrine Replacement Therapy in Clinical edited by LEONARD SHARE,1999
Practice, edited by A. WAYNE MEIKLE,2003 Menopause: Endocrinology and Management,
Early Diagnosis of Endocrine Diseases, edited edited by DAVID B. SEIFERAND ELIZABETHA.
byROBERTS. BAR,2003 KENNARD,1999
Type I Diabetes: Etiology and Treatment, edited The IGF System: Molecular Biology, Physiology,
byMARKA. SPERLING, 2003 and Clinical Applications, edited by RONG.
Handbook of Diagnostic Endocrinology, edited ROSENFELDAND CHARLEST. ROBERTS, JR., 1999
byJANET E. HALLAND LYNNETTE K. NIEMAN, Neurosteroids: A New Regulatory Function in the
2003 Nervous System,edited by ETIENNE-EMILE
Pediatric Endocrinology: A Practical Clinical BAULIEU, MICHAEL SCHUMACHER,AND PAUL
Guide, edited by SALLY RADOVICK ROBEL, 1999
AND MARGARETH. MACGILLIVRAY,2003 Autoimmune Endocrinopathies,edited by
Diseases of the Thyroid, 2nd ed., edited by ROBERT VOLPÉ,1999
LEWIS E. BRAVERMAN,2003 Hormone Resistance Syndromes, edited by
Developmental Endocrinology: From Research J. LARRY JAMESON,1999
to Clinical Practice, edited by ERICAA. Hormone Replacement Therapy, edited by
EUGSTERAND ORA HIRSCH PESCOVITZ,2002 A. WAYNE MEIKLE,1999
Osteoporosis:Pathophysiology and Clinical Insulin Resistance: The Metabolic Syndrome X,
Management, edited by ERIC S. ORWOLL edited by GERALD M. REAVENAND AMI LAWS,
AND MICHAEL BLIZIOTES,2002 1999
Challenging Cases in Endocrinology, edited by Endocrinology of Breast Cancer, edited by
MARK E. MOLITCH, 2002 ANDREA MANNI, 1999
Selective Estrogen Receptor Modulators: Molecular and Cellular Pediatric Endocrinology,
Research and Clinical Applications, edited by STUART HANDWERGER, 1999
edited by ANDREA MANNIAND MICHAELF. Gastrointestinal Endocrinology, edited by
VERDERAME,2002 GEORGEH. GREELEY, JR.,1999
Transgenics in Endocrinology, edited by
The Endocrinology of Pregnancy, edited by
MARTIN MATZUK, CHESTERW. BROWN, FULLERW. BAZER, 1998
ANDT. RAJENDRA KUMAR, 2001 Clinical Management of Diabetic Neuropathy,
Assisted Fertilization and Nuclear Transfer in
edited by ARISTIDIS VEVES, 1998
Mammals, edited by DONP. WOLF G Proteins, Receptors, and Disease, edited by
AND MARY ZELINSKI-WOOTEN, 2001 ALLEN M. SPIEGEL,1998
Adrenal Disorders, edited by ANDREWN. MARGIORIS Natriuretic Peptides in Health and Disease,
AND GEORGEP. CHROUSOS, 2001 edited by WILLISK. SAMSON
Endocrine Oncology,edited by STEPHENP. ETHIER, AND ELLIS R. LEVIN,1997
2000
Endocrinology of Critical Disease, edited by
Endocrinology of the Lung: Development
K. PATRICK OBER,1997
and Surfactant Synthesis, edited by
Diseases of the Pituitary: Diagnosis and
CAROLE R. MENDELSON, 2000 Treatment, edited by MARGARET E.
Sports Endocrinology, edited by MICHELLEP. WIERMAN,1997
WARRENAND NAAMAW. CONSTANTINI, 2000 Endocrinology of the Vasculature, edited by
Gene Engineering in Endocrinology, edited by
JAMES R. SOWERS, 1996
MARGARET A. SHUPNIK, 2000
M
ALE
H
YPOGONADISM
B , C ,
ASIC LINICAL
T P
AND HERAPEUTIC RINCIPLES
Edited by
S J. W ,
TEPHEN INTERS MD
Chief, Division of Endocrinology, Metabolism and Diabetes,
Department of Medicine, University of Louisville, Louisville, KY
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
© 2004 Springer Scienc e+Business Media New York
Originally published by Humana Press Inc. in 2004
Softcover reprint of the hardcover 1st edition 2004
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Production Editor: Robin B. Weisberg.
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ISBN 978-1-60761-739-6
Library of Congress Cataloging-in-Publication Data
Male hypogonadism : basic, clinical, and therapeutic principles / edited by Stephen J. Winters.
p. ; cm. -- (Contemporary endocrinology)
Includes bibliographical references and index.
ISBN 978-1-60761-739-6 ISBN 978-1-59259-727-7 (eBook)
DOI 10.1007/978-1-59259-727-7
1. Hypogonadism. 2. Generative organs, Male--Diseases.
[DNLM: 1. Hypogonadism. 2. Genital Diseases, Male. WK 900 M245 2004]
I. Winters, Stephen J. II. Series: Contemporary endocrinology (Totowa, N.J.)
RC898.M345 2004
616.6'8--dc21
2003013034
P
REFACE
Recent advances in cellular and molecular biology have markedly increased our
understanding of normal and abnormal hypothalamic–pituitary–testicular function. Like
other volumes in the Contemporary Endocrinology series, the goal of Male Hypo-
gonadism: Basic, Clinical, and Therapeutic Principlesis to link current knowledge of
basic biology to the practice of medicine. The development of new methods for testoster-
one replacement has substantially increased the number of men who are seeking to
determine whether they are hypogonadal, and who are using testosterone replacement
therapy, thus mandating a broader understanding of testosterone deficiency.
The chapters of this book were contributed by authors from around the world, and
from various scientific and clinical disciplines, who have devoted their careers to the
study of the physiology and pathophysiology of the male. Thus, this comprehensive and
focused volume is intended for a wide audience encompassing both basic scientists and
practicing clinicians. Its scope will provide a wealth of information for students and
fellows as well.
Chapters 1–3 review the neuroendocrine regulation of testicular function and provide
an overview of Leydig cell steroidogenesis and the normal spermatogenic process in
primates. The causes of gonadotropin deficiency and testicular failure are described in
Chapters 4–10. The impact of chronic illness on testicular function is the focus of Chap-
ters 11–13. Chapter 14 describes the endocrine mechanism for the decline in testicular
function with aging. Chapter 15 summarizes the data supporting an impact of environ-
mental factors on testicular function, whereas Chapters 16 and 17 discuss the testicular
consequences of exercise and obesity. Finally, Chapters 18 and 19 provide an overview
of androgen replacement therapy and an approach to stimulating spermatogenesis in
gonadotropin-deficient men.
I wish to thank the contributors who spent many hours researching, pondering, and
preparing their chapters, which collectively are exceedingly informative and clearly
presented.
Stephen J. Winters, MD
v
C
ONTENTS
Preface .........................................................................................................v
Contributors................................................................................................ix
1 Neuroendocrine Control of Testicular Function
Stephen J. Winters and Alan C. Dalkin ......................................................1
2 Leydig Cell Function in Man
Qiang Dong and Matthew P. Hardy.........................................................23
3 Spermatogenesis and Its Regulation in Higher Primates
Gary R. Marshall.......................................................................................45
4 Normal and Delayed Puberty
Leo Dunkel.................................................................................................63
5 Congenital Hypogonadotropic Hypogonadism: Clinical Features
and Pathophysiology
William F. Crowley and Nelly Pitteloud...................................................81
6 Male Hypogonadism Resulting From Mutations in the Genes
for the Gonadotropin Subunits and Their Receptors
Ilpo T. Huhtaniemi...................................................................................101
7 Hypogonadism in Males With Congenital Adrenal Hyperplasia
Barto J. Otten, Nike M. M. L. Stikkelbroeck,
and Ad R. M. M. Hermus ....................................................................125
8 Male Hypogonadism Resulting From Disorders of the Pituitary
and Suprasellar Region
Annamaria Colao, Giovanni Vitale, Michele De Rosa,
and Gaetano Lombardi.......................................................................139
9 Klinefelter’s Syndrome
John K. Amory and William J. Bremner.................................................159
10 Cryptorchidism
Peter A. Lee, Barry A. Kogan, and Michael T. Coughlin ......................171
11 Hypogonadism in Men With HIV-AIDS
Shalender Bhasin.....................................................................................207
12 Hypogonadism in Men With Chronic Renal Failure
Peter Y. Liu and David J. Handelsman ..................................................227
13 Male Hypogonadism Resulting From Cancer
and Cancer Treatments
Simon J. Howell and Stephen M. Shalet.................................................247
vii
viii Contents
14 An Ensemble Perspective of Aging-Related Hypoandrogenemia
in Men
Johannes D. Veldhuis, Ali Iranmanesh, and Daniel Keenan.................263
15 Environmental Causes of Testicular Dysfunction
Richard M. Sharpe...................................................................................287
16 Exercise and Male Hypogonadism: Testosterone, the Hypothalamic–
Pituitary–Testicular Axis, and Physical Exercise
Anthony C. Hackney and Jennifer Dobridge..........................................305
17 Testosterone, SHBG, and the Metabolic Cardiovascular
Syndrome
Joseph M. Zmuda and Stephen J. Winters..............................................331
18 Androgen Replacement Therapy in Hypogonadal Men
Christina Wang and Ronald S. Swerdloff...............................................353
19 Stimulation of Spermatogenesis in Hypogonadotropic Men
Marion Depenbusch and Eberhard Nieschlag .......................................371
Index ........................................................................................................387
C
ONTRIBUTORS
JOHN K. AMORY,MD • Department of Medicine, University of Washington, Seattle, WA
SHALENDER BHASIN,MD • Department of Medicine, UCLA School of Medicine,
Division of Endocrinology, Metabolism, and Molecular Medicine,
Charles R. Drew University of Medicine and Science, Los Angeles, CA
WILLIAM J. BREMNER,MD,PhD • Department of Medicine, University of Washington,
Seattle, WA
ANNAMARIA COLAO, MD, PhD • Department of Molecular and Clinical Endocrinology
and Oncology, “Federico II” University of Naples, Naples, Italy
MICHAEL T. COUGHLIN, MA • Department of Critical Care Medicine, University
of Pittsburgh School of Medicine, Pittsburgh, PA
WILLIAM F. CROWLEY, MD • Reproductive Endocrine Unit, National Center
for Infertility Research, Department of Medicine, Massachusetts General Hospital,
Boston, MA
ALAN C. DALKIN,MD• Division of Endocrinology, Department of Medicine, University
of Virginia, Charlottesville, VA
MARION DEPENBUSCH,MD • Institute of Reproductive Medicine of the University,
Münster, Germany
MICHELE DE ROSA,MD • Department of Molecular and Clinical Endocrinology
and Oncology, “Federico II” University of Naples, Italy
JENNIFER DOBRIDGE,MA • Department of Exercise and Sport Science, University
of North Carolina, Chapel Hill, NC
QIANG DONG,MD,PhD • Department of Urology, West China Hospital of Sichuan
University, Chengdu, P.R. China
LEO DUNKEL,MD• Division of Pediatric Endocrinology, Hospital for Children
and Adolescents, Helsinki, Finland
ANTHONY C. HACKNEY,PhD,FACSM • Department of Exercise and Sport Science,
Department of Nutrition, School of Public Health, and Department
of Cell-Molecular Physiology , School of Medicine, University of North Carolina,
Chapel Hill, NC
DAVID J. HANDELSMAN,MBBS,PhD • ANZAC Research Institute, University of Sydney,
Sydney, Australia
MATTHEW P. HARDY,PhD • Center for Biomedical Research, Population Council
and the Rockefeller University, New York, NY
AD R. M. M. HERMUS,PhD,MD • Department of Endocrinology, University Medical
Center Nijmegen, Nijmegen, The Netherlands
SIMON J. HOWELL,MD,MRCP • Department of Endocrinology, Christie Hospital NHS
Trust, Manchester, United Kingdom
ILPO T. HUHTANIEMI,MD,PhD• Institute of Reproductive and Developmental Biology,
Imperial College London, Faculty of Medicine, London, United Kingdom
ALI IRANMANESH, MD • Endocrine Section, Medical Service, Salem Veterans Affairs
Medical Center, Salem, VA
ix
x Contributors
DANIEL KEENAN,PhD • Department of Statistics, University of Virginia,
Charlottesville, VA
BARRY A. KOGAN, MD • Division of Urology, Albany Medical College, Albany, NY
PETER A. LEE, MD, PhD • Department of Pediatrics, Penn State College of Medicine,
The Milton S. Hershey Medical Center, Hershey, PA
PETER Y. LIU,MBBS,PhD • Department of Andrology, Concord Hospital, ANZAC
Research Institute, University of Sydney, Sydney , Australia
GAETANO LOMBARDI,MD • Department of Molecular and Clinical Endocrinology
and Oncology, “Federico II” University of Naples, Italy
GARY R. MARSHALL,PhD • Department of Medicine, Division of Endocrinology
and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA
EBERHARD NIESCHLAG,MD • Institute of Reproductive Medicine of the University
of Münster, Münster, Germany
BARTO J. OTTEN,MD,PhD • Department of Pediatric Endocrinology, University
Medical Center Nijmegen, Nijmegen, The Netherlands
NELLY PITTELOUD,MD• Reproductive Endocrine Unit, Department of Medicine,
National Center for Infertility Research, Massachusetts General Hospital, Boston, MA
STEPHEN M. SHALET,MD,FRCP • Department of Endocrinology, Christie Hospital NHS
Trust, Manchester, United Kingdom
RICHARD M. SHARPE,PhD • MRC Human Reproductive Sciences Unit, Centre
for Reproductive Biology, University of Edinburgh, Edinburgh, United Kingdom
NIKE M. M. L. STIKKELBROECK,PhD,MD • Department of Pediatric Endocrinology, Uni-
versity Medical Center Nijmegen, Nijmegen, The Netherlands
RONALD S. SWERDLOFF,MD• Division of Endocrinology, Department of Medicine,
Harbor-UCLA Medical Center and Research and Education Institute, Torrance, CA
JOHANNES D. VELDHUIS,MD • Endocrine Research Unit, Mayo Clinic and Foundation,
Rochester, MN
GIOVANNI VITALE,MD • Department of Molecular and Clinical Endocrinology
and Oncology, “Federico II” University of Naples, Italy
CHRISTINA WANG,MD • Division of Endocrinology, Department of Medicine, Harbor-
UCLA Medical Center and Research and Education Institute, Torrance, CA
STEPHEN J. WINTERS,MD • Division of Endocrinology, Metabolism and Diabetes,
Department of Medicine, University of Louisville, Louisville, KY
JOSEPH M. ZMUDA,PhD • Department of Epidemiology, Graduate School of Public
Health, University of Pittsburgh, Pittsburgh, PA
