Pharmacology, Doping and Sports The work of dope testers is constantly being obstructed by the development of ever harder-to-trace new forms of banned substances.Organisations such as the World Anti-Doping Association and the United States Anti-Doping Agency are pioneering cutting-edge techniques designed to keep competition at the highest level fair and safe, and must ensure that their drug-testing laboratories adhere to the highest scientific standards. In Pharmacology, Doping and Sports,these techniques and procedures are explained by the anti- doping experts who practice them. Broad-ranging in scope, this book examines the effects of performance- enhancing substances on the athlete’s health and the role of anti-doping procedures as an ethical question. Additionally, it explains the background to, and the emergence of, the anti-doping movement. The book also offers in-depth analysis of key scientific matters,such as: • standardanalytical and diagnostic tests for sports doping • regulatory standards for laboratory proficiency • common performance-enhancing techniques such as anabolic and designer steroids,blood doping,growth hormones,and gene doping • carbon isotope ratio testing Written by some of the world’s leading authorities on the science of sports doping, Pharmacology, Doping and Sports provides an invaluable study of up-to-the-minute anti-doping techniques.This book is essential reading for all sports scientists,coaches,policy-makers,students and athletes interested in the science or ethics of doping in sport. Jean L Fourcroy is a regulatory consultant in urology and endocrinology, and a leading authority on the science ofanti-doping.She has been appointed to the Board of the United States Anti-Doping Agency,is an active member of the American Urological Association and the American Society of Andrology, and is a Past President of the American Medical Women’s Association. Pharmacology, Doping and Sports A scientific guide for athletes, coaches, physicians, scientists and administrators Edited by Jean L Fourcroy First published 2009 by Routledge 2Park Square,Milton Park,Abingdon,Oxon OX144RN Simultaneously published in the USA and Canada byRoutledge 270 Madison Ave,New York,NY 10016 This edition published in the Taylor & Francis e-Library, 2008. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” Routledge is an imprint ofthe Taylor & Francis Group,an informa business ©2009 Jean L Fourcroy,selection and editorial matter; individual chapters,the contributors All rights reserved.No part ofthis book may be reprinted or reproduced or utilized in any form or by any electronic,mechanical,or other means,now known or hereafter invented,including photocopying and recording,or in any information storage or retrieval system,without permission in writing from the publishers. British Library Cataloguing in Publication Data Acatalogue record for this book is available from the British Library Library ofCongress Cataloging-in-Publication Data Pharmacology,doping and sports:a scientific guide for athletes,coaches, physicians,scientists and administrators / edited by Jean L.Fourcroy. p.;cm. Includes bibliographical references. 1.Doping in sports.I.Fourcroy,Jean L. [DNLM:1.Doping in Sports—methods.2.Anabolic Agents—adverse effects.3.Doping in Sports—ethics. 4.Steroids—adverse effects.5.Substance Abuse Detection—methods.QT 261 P5362008] RC1230.P532008 362.29–dc22 2008011128 ISBN 0-203-89104-X Master e-book ISBN ISBN10:0–415–42845–9 (hbk) ISBN10:0–203–89104–X (ebk) ISBN13:978–0–415–42845–3 (hbk) ISBN13:978–0–203–89104–9 (ebk) Contents Notes on contributors vii Foreword xi Preface xiii Prologue:an athlete’s perspective xv Acknowledgments xvii List of abbreviations xviii 1 The historical and scientificpathway to fair and accurate testing 1 JEAN L FOURCROY AND BAARON PITTINGER 2 Ensuring quality results in a global testing system 9 LARRYDBOWERS 3 Anabolic-androgenic steroids:Historical background, physiology,typical use and side effects 23 RICHARD VCLARK 4 Testing for anabolic agents 37 CHRISTIANE AYOTTE 5 The art of ferreting out a designer steroid 55 LARRY D BOWERS 6 Isotope ratio mass spectrometry:Carbon isotope ratio analysis 61 RODRIGO AGUILERA 7 Stimulants,diuretics and masking of doping in sport 91 RICHARD L HILDERBRAND 8 Erythropoietin doping:Detection in urine 107 FRANÇOISE LASNE 9 Erythrocyte volume expansion and human performance 125 MICHAEL N SAWKA,STEPHEN R MUZA ANDANDREW J YOUNG vi Contents 10 Growth hormone,secretogogues and related issues 135 PETER H SÖNKSEN ANDRICHARD HOLT 11 Gene doping 167 THEODORE FRIEDMANN 12 Therapeutic gene use 171 JEAN L FOURCROY 13 Doping and its impact on the the healthy athlete 177 ANDREW PIPE 14 Conclusions 199 JEANLFOURCROY Index 209 Notes on contributors Dr Rodrigo Aguilera completed his B.Sc. M.S. at the university of Lyon and Ph.D. at the CNRS Mass Spectrometry Laboratory in the Chemistry and Biology department.At the CNRS he worked for 5 years to develop a new approach to the detection of performance-enhancing drugs used by profes- sional athletes by measuring the Carbon Isotope Ratio Mass Spectrometry (IRMS). He was then employed at the Olympic Analytical Laboratory headed by Dr Don Catlin in the Department of Medical and Molecular Pharmacology at UCLA where he worked for 4 years. Using the IRMS detection method he developed while in France, Dr Aguilera became an authority in this field, and was one of the pioneers in the application of IRMS to identify the use of exogenous testosterone.He was responsible for the drug testing analysis by IRMS at the Atlanta Summer Olympics, Salt Lake City Winter Olympics and the 2007 Pan American Games as well as at other sporting events. Since joining the Mass Spectrometry Laboratory at UCLA in 2002 Dr Aguilera expanded his experience to the field of pro- teomics. Dr Aguilera has worked closely with Dr Julian Whitelegge on a US Department of Energy funded project investigating the proteomics of a blue-green alga. In 2003 Dr Aguilera helped to establish and directed the University of Southern California Proteomics Core Facility Laboratory. Since 2006 Dr Aguilera has established and directed the Proteomics Core Facility at the House Ear Institute. Christiane Ayottehas been Director of the Doping Control Laboratory,INRS – Institut Armand-Frappier, Quebec, since 1991. She has been a member of the IAAF Doping Commission since 1995 and of the IOC Working Group on Harmonization of Laboratory Protocols since 1996, and was elected representative of the Heads of IOC Accredited Laboratories in 1995–6. Larry D Bowers serves on the WADA Laboratory Accreditation Sub- committee. He served as Deputy Director of the drug-testing laboratory for the 1996 Olympic Games in Atlanta and 1999 Pan Am Games in Canada. He also received the MCF LS Palmer Award for outstanding contributions to chromatography in 1985, and the annual Franklin & viii Notes on contributors Marshall College Alumni Citation in 2007 for distinguished professional contributions. Richard V Clark is a Clinical Researcher in Endocrinology and Metabolism, and a Group Director in Metabolic Discovery Medicine and Clinical Pharmacology at GlaxoSmithKline.Prior to moving to GSK,Dr Clark was in academic medicine, initially on faculty at Emory University School of Medicine,Atlanta,and then at Duke University Medical Center,Durham. He is a past president of the American Society of Andrology. Jean L Fourcroyis a regulatory consultant in urology and endocrinology,and aleading authority on the science ofanti-doping.She has been appointed to the Board of USADA and is an active member of the American Urological Association and the American Society of Andrology,and past president of the American Medical Women’s Association. Theodore Friedmann is Professor of Pediatrics at the Center for Molecular Genetics, School of Medicine, University of California, San Diego. The primary area of research for his laboratory is gene therapy. Professor Friedmann was named president of the American Society of Gene Therapy in 2006.He is also Director of the interdepartmental UCSD Gene Therapy Program and Whitehill Chair of Biomedical Ethics. Richard L Hilderbrand joined USADA in March 2003 as Science Director, where he currently manages the Therapeutic Use Exemption process.He is retired from the Navy, where his last assignment was at the Office of the Secretary of Defense,The Pentagon, where he had primary responsibility for drug abuse reduction programs for the military services. Richard Holt became Reader in Endocrinology and Metabolism at the University ofSouthampton in 2006.His current research interests are broadly focused around the GH–IGF axis and the pathogenesis of the insulin resistance syndrome.These studies have led on to research into the develop- ment of a test for the detection of GH abuse in sport. He has acted as an adviser to WADAand USADA. Françoise Lasne is head of the Research and Biological Development Department at the French National Anti-Doping Laboratory. Dr Lasne developed the first urine test for detection of recombinant human erythro- poietin (EPO) in 1999.This form of testing,first used in Sydney at the 2000 Olympic Games,is now used by all international anti-doping agencies. Stephen Muzais a research physiologist at the US Army Research Institute of Environmental Medicine in Natick, MA. Dr Muza has investigated high- altitude sickness,physiological adaptations to high altitude,human perform- ance at high altitude and control of respiration. He has authored over 100 peer-reviewed articles in scholarly journals,and many textbook chapters. Notes on contributors ix Andrew Pipe is the Director of the Minto Prevention and Rehabilitation Centre at the University of Ottawa Heart Institute.He is also a Professor at the Faculty of Medicine,University of Ottawa,Ontario,Canada.He was the founding Chair of Physicians for a Smoke-Free Canada and was made an honorary life member of the Canadian Council on Smoking and Health in 1989.In addition,he is Team Physician for the Canadian National Men’s Basketball Team and Chair Emeritus of the Canadian Centre for Ethics and Sport. Baaron Pittingerjoined the United States Olympic Committee (USOC) in 1977 as Director of Special Events. He subsequently served the USOC as Assistant Executive Director (1981–7) and Executive Director (1988–90) prior to being named Executive Director of US Hockey (1990–3).Pittinger was awarded the prestigious Olympic Order by the International Olympic Committee in 1992. Michael N Sawkais Chief of the Thermal and Mountain Medicine Division at the U.S.Army Research Institute ofEnvironmental Medicine in Natick,MA. His research interests are environmental and exercise physiology, fluid/ electrolyte balance and rehabilitation medicine. He has authored over 200 peer-reviewed articles in scholarly journals,and many textbook chapters. Peter H Sönksen is Emeritus Professor of Endocrinology at St Thomas’ Hospital and King’s College London,and Visiting Professor at Southampton University Medical School. Professor Sönksen’s group were the first to dis- cover the syndrome of “growth hormone deficiency in adults”(1991) and to demonstrate the benefits of growth hormone replacement (1989). He has worked for the IOC Medical Commission as an expert on growth hormones. Carl Swenson has been a USADA Board Member since 2007, and is attend- ing the University of Utah S.J.Quinney School of Law.He represented the United States both in mountain biking and in cross-country skiing,appear- ing as a representative in the latter at the 1994, 2002 and 2006 Olympic Winter Games. Travis TTygartis the ChiefExecutiveOfficer ofthe United States Anti-Doping Agency(USADA).As part of his duties,he investigated the BALCO doping conspiracy,and arbitrated over 30 cases before the AAA or CAS,including the cases of Tim Montgomery,Michelle Collins andChryste Gaines.He was involved with drafting the USADA Protocol for Olympic Movement Testing and the World Anti-Doping Agency’s Code. Andrew J Youngis a research physiologist and Chief of the Military Nutrition Division atthe US Army Research Institute of Environmental Medicine in Natick,MA.Dr Young has investigated the biological basis for,and strate- gies to mitigate, performance degradations in people exposed to stressors such as intense physical exertion, nutritional deprivation and exposure to extremes of heat,cold and high altitude.
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