E. Nieschlag H. M. Behre (Eds.) Testosterone

Transcription

1 E. Nieschlag H. M. Behre (Eds.) Testosterone

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3 E. Nieschlag H. M. Behre (Eds.) Testosterone Action - Deficiency - Substitution Second Edition Editorial Assistant: S. Nieschlag With Contributions by 1. E. Atkinson H. M. Behre S. Bhasin R. Bross R. Casaburi Y.-L. Chang K. Christiansen B. Couzinet A. von Eckardstein J. S. Finkelstein J. Frick L.J. Gooren D. J. Handelsman A. Jungwirth J.M. Kaufman P. Y. Liu W.A. Meikle E. Nieschlag C.A. Quigley Y.A. Randall EEG. Rommerts E. Rovan G. Schaison W. Schanzer P.J. Snyder T. W. Storer A. Vermeulen G. E Weinbauer With 95 Figures and 28 Tables, Springer

4 Prof. Dr. med. Eberhard Nieschlag Priv.-Doz. Dr. med. Hermann M. Behre Institute of Reproductive Medicine, University of Munster Domagkstrasse 11, D Munster, Germany Editorial Assistant: Susan Nieschlag, MA ISBN -13: e-isbn -13: DOl: / Library of Congress Cataloging-in Publication Data Testosterone: action, deficiency, substitution / E. Nieschlag, H. M. Behre (eds.); editorial assistant, S. Nieschlag; with contributions by L. E. Atkinson... [et al.]. - 2nd ed. Includes bibliographical references and index. ISBN-13: Testosterone - Therapeutic use. 2. Testosterone - Physiological effect. 1. Nieschlag. E. II. Behre, H.M. (Hermann M.), RM296.5.T47T '.366-dc21 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 1990, 1998 Softcover reprint of the hardcover 2nd edition 1998 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. production: PRO EDIT GmbH, Heidelberg Illustrations: G. Hippmann, Niirnberg Typesetting (Data conversion): K+V Fotosatz GmbH, Beerfelden Cover-Design: E. Kirchner, Heidelberg SPIN / Printed on acid-free paper

5 Preface The first edition of "Testosterone: Action, Deficiency, Substitution" was published in Since then our understanding of the hormone that turns males into men has tremendously increased. Therefore, the editors felt that a second extended edition of the book is warranted in order to summarize established and recent findings in the field and to present the reader with an up-to-date textbook. The increased mass of knowledge is reflected by the growth of the volume from 14 to 20 chapters. In the updated edition the biochemistry and metabolism of androgens have been complemented by extensive information on the molecular biology of the androgen receptor and its disorders. The key role of testosterone in spermatogenesis is now better defined. We have a more complete understanding of the psychotropic effects of testosterone and know so much about the different target organs and functions that individual chapters deal with testosterone and the prostate, lipids and the cardiovascular system, hair, bones and muscles. The general chapter on pharmacology and clinical uses of testosterone, in particular in male hypogonadism, is extended by pharmacokinetic studies on testosterone preparations and individual substitution modalities using testosterone esters as well as implants and advanced trans dermal applications. The physiologic basis and possible clinical applications of testosterone in non-gonadal diseases, in male senescence, in hormonal male contraception and in transsexuals are discussed. The last chapter describes the role of "investigative" steroid biochemistry applied to tracking anabolic steroid abuse. In order to synchronize the writing of the various chapters the authors met on January 22-25, 1998 at Castle Elmau, Bavaria, for final editing of their previously submitted chapters. This guaranteed that all chapters were concluded simultaneously and reflect precisely the state of current knowledge. The contributors deserve our appreciation for their prompt and reliable cooperation in this venture. We are grateful for a generous grant from SmithKline Beecham Pharma (Munich) facilitating the meeting

6 VI Preface of the authors in combination with a Symposion open to professionals interested in the topic. The splendid isolation of Castle Elmau high up in the Bavarian Alps provided a congenial atmosphere for a productive meeting. Much of the editorial work was performed by Susan Nieschlag M. A. whose untiring professional help is gratefully acknowledged. Barbel Bahnes, Kerstin Neuhaus and Angelika Schick helped with the word processing of the manuscripts. Finally we would like to thank Dr. Carol Bacchus and the Springer-Verlag for supporting the project and producing the book. Munster/SchloB Elmau, April 1998 Eberhard Nieschlag Hermann M. Behre

7 Table of Contents 1. Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions F. F. G. Rommerts 2. The androgen receptor: Physiology and pathophysiology C. A. Quigley Behavioural correlates of testosterone K. Christiansen 4. The role of testosterone in spermatogenesis G. F. Weinbauer and E. Nieschlag 5. Androgens and hair V. A. Randall 6. Androgens and bone metabolism J. S. Finkelstein 7. Androgens and muscles S. Bhasin, R. Bross, T. W. Storer and R. Casaburi 8. Androgens, cardiovascular risk factors and atherosclerosis 229 A. von Eckardstein 9. Androgens and the prostate J. Frick, A. Jungwirth and E. Rovan 10. Pharmacology and clinical uses of testosterone E. Nieschlag and H. M. Behre 11. Comparative pharmacokinetics of testosterone esters 329 H. M. Behre and E. Nieschlag 12. Clinical pharmacology of testosterone pellet implants D. J. Handelsman

8 VIII Table of Contents 13. Long-term experience with testosterone replacement through scrotal skin L.E. Atkinson, Y.-L. Chang and P.J. Snyder 14. A permeation-enhanced non-scrotal testosterone transdermal system for the treatment of male hypogonadism W.A. Meikle 15. Percutaneous dihydrotestosterone treatment G. Schaison and B. Couzinet Androgens in male senescence J. M. Kaufman and A. Vermeulen 17. Androgen therapy in non-gonadal disease P. Y. Liu and D. J. Handelsman 18. Testosterone in male contraception E. Nieschlag and H. M. Behre 19. Androgen treatment of female-to-male transsexuals 529 L.J. Gooren 20. Abuse of androgens and detection of illegal use W. Schiinzer Subject Index

9 List of Contributors Atkinson, L. E. ALZA Corporation, 950 Page Mill Road, Palo Alto, CA , USA Behre, H.M. Institute of Reproductive Medicine, University of Miinster, Domagkstr. 11,48129 Miinster, Germany Bhasin, s. Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1621 E 120th Street, MP-02, Los Angeles, CA 90059, USA Bross, R. Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1621 E 120th Street, MP-02, Los Angeles, CA 90059, USA Casaburi, R. Division of Respiratory Medicine, Pulmonary Physiology, and Critical Care Medicine, Harbor-UCLA Medical Center, Torrance CA 90502, USA Chang, Y.-L. ALZA Corporation, 950 Page Mill Road, Palo Alto, CA , USA Christiansen, K. Institute for Human Biology of the University, Allende-Platz 2, Hamburg, Germany Couzinet, B. Department of Endocrinology and Reproductive Medicine, Centre Hospitalier de Bicetre, 78, rue du General Leclerc, Kremlin-Bicetre, France von Eckardstein, A. Institute of Clinical Chemistry and Laboratory Medicine, Central Laboratory, Albert -Schweitzer-Str. 33, Miinster, Germany Finkelstein, J. S. Endocrinology Unit, Massachusetts General Hospital, Bulfinch Fruit Street, Boston, MA 02114, USA Frick, J. Department of Urology, Hospital Salzburg, General Hospital, Miillner Hauptstr. 48, 5020 Salzburg, Austria Gooren, L. J. Dept. of Endocrinology, Free University Hospital, P. O. Box 7057, 1007 MB Amsterdam, The Netherlands

10 X List of Contributors Handelsman, D.J. Andrology Unit, Department of Medicine and Obstetrics/Gynecology (D02), University of Sydney, Sydney 2006, NSW, Australia Jungwirth, A. Department of Urology, Salzburg General Hospital, Mullner Hauptstr. 48, 5020 Salzburg, Austria Kaufman, J. M. Department of Endocrinology, Academish Ziekenhuis, 185 de Pintelaan, 9000 Gent, Belgium Liu, P. Y. Andrology Unit, Department of Medicine and Obstetrics/Gynecology (D 02), University of Sydney, Sydney 2006, NSW, Australia Meikle, W. A. Division of Endocrinology, University of Utah Medical School, 50 North Medical Drive, Salt Lake City, UT , USA Nieschlag, E. Institute of Reproductive Medicine, University of Munster, Domagkstr. 11, Munster, Germany Quigley, C. A. Department of Pediatrics, Indiana University Medical Center, 702 Barnhill Drive, Indianapolis, Indiana , USA Randall, V. A. Department of Biomedical Sciences, Richmond Building, University of Bradford, Richmond Road, Bradford BD 7 1 DP, United Kingdom Rommerts, F. F. G. Department of Endocrinology and Reproduction, Erasmus University Rotterdam, P. O. Box 1738, 3000 DR Rotterdam, The Netherlands Rovan, E. Department Urology, Salzburg General Hospital, Miillner Hauptstr. 48, 5020 Salzburg, Austria Schaison, G. Department of Endocrinology and Reproductive Medicine, Centre Hospitalier de Bicetre, 78, rue du General Leclerc, Kremlin-Bicetre, France Schanzer, W. Institute of Biochemistry, German Sports University Kaln, Carl-Diem-Weg 6, Kaln, Germany Snyder, P.J. Department of Medicine, University of Pennsylvania, 520 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA , USA Storer, T. W. Laboratory of Exercise Science, EI Camino College, Torrance, CA 90502, USA Vermeulen, A. Maaltemeers 33, 9052 Ghent-Zwijnaarde, Belgium Weinbauer, G. F. Institute of Reproductive Medicine, University of Munster, Domagkstr. 11,48129 Munster, Germany