Table Of Content

E. Nieschlag H. M. Behre (Eds.) Testosterone Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Santa Clara Singapore Tokyo 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 Prof. Dr. med. Eberhard Nieschlag Priv.-Doz. Dr. med. Hermann M. Behre Institute of Reproductive Medicine, University of Munster Domagkstrasse 11, D-48129 Munster, Germany Editorial Assistant: Susan Nieschlag, MA ISBN -13: 978-3-642-72187-8 e-ISBN -13: 978-3-642-72185-4 DOl: 10.1007/978-3-642-72185-4 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-13:978-3-642-72187-8 1. Testosterone - Therapeutic use. 2. Testosterone - Physiological effect. 1. Nieschlag. E. II. Behre, H.M. (Hermann M.), 1961- . RM296.5.T47T47 1998 615'.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 illus trations, 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. Viola tions 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 publica tion 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 10566757 13/3135-5 4 3 2 1 0 - Printed on acid-free paper Preface The first edition of "Testosterone: Action, Deficiency, Substitu tion" was published in 1990. 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 de fined. We have a more complete understanding of the psychotro pic 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 sys tem, hair, bones and muscles. The general chapter on pharmacol ogy and clinical uses of testosterone, in particular in male hypo gonadism, is extended by pharmacokinetic studies on testoster one preparations and individual substitution modalities using testosterone esters as well as implants and advanced trans dermal applications. The physiologic basis and possible clinical applica tions of testosterone in non-gonadal diseases, in male senes cence, 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 coopera tion in this venture. We are grateful for a generous grant from SmithKline Beecham Pharma (Munich) facilitating the meeting VI Preface of the authors in combination with a Symposion open to profes sionals interested in the topic. The splendid isolation of Castle Elmau high up in the Bavarian Alps provided a congenial atmo sphere for a productive meeting. Much of the editorial work was performed by Susan Nieschlag M. A. whose untiring professional help is gratefully acknowl edged. 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 Table of Contents 1. Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions 1 F. F. G. Rommerts 2. The androgen receptor: Physiology and pathophysiology 33 C. A. Quigley 3. Behavioural correlates of testosterone • . . . . . . . . . . . . .. 107 K. Christiansen 4. The role of testosterone in spermatogenesis .......... 143 G. F. Weinbauer and E. Nieschlag 5. Androgens and hair ........................... 169 V. A. Randall 6. Androgens and bone metabolism . . . . . . . . . . . . . . . . .. 187 J. S. Finkelstein 7. Androgens and muscles ........................ 209 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 ..................... 259 J. Frick, A. Jungwirth and E. Rovan 10. Pharmacology and clinical uses of testosterone ........ 293 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 ................... 349 D. J. Handelsman VIII Table of Contents 13. Long-term experience with testosterone replacement through scrotal skin .......................... 365 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 ..................•..... 389 W.A. Meikle 15. Percutaneous dihydrotestosterone treatment 423 G. Schaison and B. Couzinet 16. Androgens in male senescence .................. 437 J. M. Kaufman and A. Vermeulen 17. Androgen therapy in non-gonadal disease. . • . . . . . . . . 473 P. Y. Liu and D. J. Handelsman 18. Testosterone in male contraception. . . • . . . . . . . . • . . . 513 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 ...... 545 W. Schiinzer Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 567 List of Contributors Atkinson, L. E. Christiansen, K. ALZA Corporation, Institute for Human Biology 950 Page Mill Road, of the University, Palo Alto, CA 94394-0802, USA Allende-Platz 2, 20146 Hamburg, Germany Behre, H.M. Institute of Reproductive Medicine, Couzinet, B. University of Miinster, Department of Endocrinology Domagkstr. 11,48129 Miinster, and Reproductive Medicine, Germany Centre Hospitalier de Bicetre, 78, rue du General Leclerc, Bhasin, s. Division of Endocrinology, 94275 Kremlin-Bicetre, France Metabolism and Molecular Medicine, Charles R. Drew University von Eckardstein, A. of Medicine and Science, Institute of Clinical Chemistry 1621 E 120th Street, MP-02, and Laboratory Medicine, Central Los Angeles, CA 90059, USA Laboratory, Albert -Schweitzer-Str. 33, 48129 Miinster, Germany Bross, R. Division of Endocrinology, Finkelstein, J. S. Metabolism and Molecular Medicine, Endocrinology Unit, Massachusetts Charles R. Drew University General Hospital, Bulfinch 327 - of Medicine and Science, Fruit Street, Boston, MA 02114, USA 1621 E 120th Street, MP-02, Los Angeles, CA 90059, USA Frick, J. Department of Urology, Casaburi, R. Hospital Salzburg, General Hospital, Division of Respiratory Medicine, Miillner Hauptstr. 48, Pulmonary Physiology, and Critical 5020 Salzburg, Austria Care Medicine, Harbor-UCLA Medical Center, Torrance CA 90502, USA Gooren, L. J. Dept. of Endocrinology, Chang, Y.-L. Free University Hospital, ALZA Corporation, P. O. Box 7057, 950 Page Mill Road, 1007 MB Amsterdam, Palo Alto, CA 94304-0802, USA The Netherlands