Androgen Abuse in Athletes: Detection and Consequences

S P E C I A L C l i n i c a l F E A T U R E R e v i e w Androgen Abuse in Athletes: Detection and Consequences Shehzad Basaria Division of Endocrinology and Metabolism, Boston University School of Medicine, Boston, Massachusetts 02118 Evidence Acquisition: The PubMed and Google Scholar search engines were used to identify publications addressing various forms of doping, methods employed in their detection, and adverse effects associated with their use. Evidence Synthesis: The list of drugs prohibited by the World Anti-Doping Agency (WADA) has grown in the last decade. The newer entries into this list include gonadotropins, estrogen antagonists, aromatase inhibitors, androgen precursors, and selective androgen receptor modulators. The use of mass spectrometry has revolutionized the detection of various compounds; however, challenges remain in identifying newer designer androgens because their chemical signature is unknown. Development of high throughput bioassays may be an answer to this problem. It appears that the use of AAS continues to be associated with premature mortality (especially cardiovascular) in addition to suppressed spermatogenesis, gynecomastia, and virilization. Conclusion: The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. The development of sensitive detection techniques may help discourage (at least to some extent) the abuse of these compounds. Investigations are needed to identify ways to hasten the recovery of the gonadal axis in AAS users and to determine the mechanism of cardiac damage by these compounds. (J Clin Endocrinol Metab 95: 1533–1543, 2010) here was a collective failure to recognize the problem as it emerged and to deal with it early on.” Senator George J. Mitchell, “Steroid Report”, December 2007. The culture of using ergogenic (performance enhancing) compounds among athletes dates back to the initial Olympiad in ancient Greece where herbal remedies and animal extracts were apparently used by the athletes before the competition. Hence, the history of “doping” began long before the discovery of androgens. Not surprisingly, soon after their discovery, androgens made their way on the list of ergogenic com- “T pounds. Although androgens were used in various sporting events, they only received major attention once their use became apparent in the Olympic Games. The most notorious era in the doping history of the Olympic Games was the use of anabolic-androgenic steroids (AAS) by the athletes (mainly women) of the German Democratic Republic (1960s to 1980s) (1). However, it wasn’t until 1967 that the International Olympic Committee (IOC) released its first list of banned drugs. In 1974, AAS abuse was prohibited by the IOC (2). Currently, the scrutiny of doping in sports is conducted by ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2010 by The Endocrine Society doi: 10.1210/jc.2009-1579 Received July 23, 2009. Accepted January 6, 2010. First Published Online February 5, 2010 Abbreviations: AAS, Anabolic-androgenic steroid(s); hCG, human chorionic gonadotropin; IRMS, isotope ratio mass spectrometry; SARM, selective androgen receptor modulator; T/E, testosterone/epitestosterone. J Clin Endocrinol Metab, April 2010, 95(4):1533–1543 jcem.endojournals.org 1533 Context: Doping with anabolic androgenic steroids (AAS) both in sports (especially power sports) and among specific subsets of the population is rampant. With increasing availability of designer androgens, significant efforts are needed by antidoping authorities to develop sensitive methods to detect their use. 1534 Basaria Androgen Abuse in Athletes TABLE 1. Locations of the 35 accredited laboratories of the WADA Continent (n) Asia (6) Africa (2) Australia (1) Europe (20) South and Central America (3) a subsidiary of IOC called the World Anti-Doping Agency (WADA), which was formed a decade ago. Although based in Montreal, WADA currently has a network of 35 international doping control laboratories (Table 1). Every year WADA publishes its ever-growing list of prohibited drugs; however, androgens remain the most commonly used ergogenic drugs in sports (3). The discovery of selective androgen receptor modulators (SARMs) has introduced another potential avenue for abuse among the athletic community. Hence, in January 2008, WADA also announced banning of SARMs from the Olympic Games. Table 2 lists the current list of prohibited drugs used for direct and indirect doping. History of AAS Abuse Almost half a century before the discovery of androgens, Brown-Sequard (the father of andrology) had recognized that the contents of testicular extracts could improve libido, energy, and muscle strength (4, 5). After synthesis of testosterone, Boje (6) was the first to suggest that sex hormones may enhance physical performance. Although the most well-known phase of AAS abuse in Olympic history is that of the Soviet weight-lifting team in the 1952 and 1956 Olympic Games, it is believed that some German athletes were given androgens even during the 1936 Berlin Olympics (7). The introduction of AAS among the American athletes is attributed to Dr. John Ziegler (a physicianmember of the U.S. Weight-Lifting Team) who learned about the use of AAS by the Russian team in 1954 during his trip to weight-lifting championships in Vienna (8). Upon his return, Dr. Ziegler experimented with testosterone on weight lifters in the York Babel Club in Pennsylvania. That is considered to be the beginning of AAS abuse in sports in the United States, which later spread from high-intensity strength-training games to sports such as field athletics, baseball, swimming, etc. The two common patterns of AAS abuse are “stacking” and “cycling.” Stacking involves the use of two or more androgens in progressively increasing doses over a short period of time. Cycling refers to the intermittent use of AAS where use of steroids is followed by a drug holiday. The practice of TABLE 2. The 2009 WADA list of prohibited androgens and androgen modulators Exogenous AAS Androstendiol Androstendione Bolandiol Bolasterone Calusterone Desoxymethyltestosterone Fluoxymesterone Mestanolone Mesterolone Methandienone Methyltestosterone Methylnortestosterone Nandrolone Oxandrolone Oxymesterone Oxymetholone Stanozolol Testosterone Tetrahydrogestrinone Tibolone Trenbolone Endogenous AAS Androstendiol Androstendione Dihydrotestosterone Testosterone Epitestosterone Gonadotropins hCG (men) LH (men) Androgen modulators Aromatase inhibitors Antiestrogens Androstendione DHEA Other SARMs North America (3) Country (city) China (Beijing), India (New Delhi), Japan (Tokyo), Korea (Seoul), Malaysia (Penang), Thailand (Bangkok) Republic of South Africa (Bloemfontein), Tunisia (Tunis) Australia (Sydney) Austria (Seibersdorf), Belgium (Ghent), Czech Republic (Prague), Finland (Helsinki), France (Paris (...truncated)