Doping in sport: misuse, analytical tests, and legal aspects.

As part of the International Congress of Clinical Chemistry, a symposium, Doping in Sport: Misuse, Analytical Tests, and Legal Aspects, was held, a week before the start of the Olympic Games at Atlanta, bringing together a number of international experts concerned with various aspects of controlling drug abuse in sport. The presentations focused particularly on anabolic-androgenic steroids (AAS), these analytes still comprising the greatest number of positive findings in samples tested by International Olympic Committee (IOC)-accredited sports drug-testing laboratories. Although various aspects of AAS use and detection have been reported on in the last decade, the proceedings of this symposium, published in this issue of Clinical Chemistry, bring together health, social, endocrine, and analytical perspectives in a widely read peer-reviewed journal. Those who think that the harmful effects of AAS administration are relatively benign and perhaps should not be banned by the IOC may find particularly sobering the article by Franke and Berendonk [1 ], which describes the health and social consequences of the clandestine state-sponsored program of administration of AAS in the former East Germany. This article should be extremely useful for educational purposes and, we hope, will encourage some present users to abandon the practice. The mechanism of action of AAS is still not well understood, and the article by Wu [2 ] is a useful update. Catlin et al. [3 ] discuss the pertinent issues of detecting AAS administration, in particular of testosterone (T), which is commonly abused. Stenman et al. [4 ] give a clinical chemistry perspective on the problems of detecting human chorionic gonadotropin (hCG) by immunoassay, the protein hormone that may be used by competitors to stimulate testicular production of T. Bowers [5 ] discusses analytical advances to detect performance-enhancing compounds, particularly with reference to xenobiotic AAS and peptide hormones, such as hCG. But why bother about anabolic steroids? Attention began to focus on the steroid problem in modern-day sports with the allegation that Soviet weightlifters were administering T to gain strength in the early 1950s [6 ]. The problem became greater with the advent of synthetic analogs designed to enhance the anabolic properties. Nandrolone, the 19-nor analog of T, was the first compound to show enough myotrophic-androgenic dissociation in animal experiments [7 ] to justify its introduction in clinical therapy as an anabolic steroid [8 ]. With the development of nandrolone, studies on numerous substituted and hydrogenated analogs of T soon followed. Many US patents were awarded to drug companies around 1960, e.g., methandrostenolone to Ciba (1959), oxymesterone to Farmitalia (1960), stanozolol to Sterling Drug (1962) [9 ]. Clinically, there was great hope for the use of these drugs in promoting protein anabolism without evoking a strong androgenic effect. However, some sporting competitors also desired these drugs, in preference to T, for the same reasons. In 1967 the IOC Medical Commission banned the practice of doping in sport; at that time, anabolic steroids were not included in the banned class of compounds because there was no test for them. Nonetheless, use of anabolic steroids at international level was perceived to be rife; e.g., a decathlon athlete, Dr. Tom Wadell, told the New York Times that he estimated about a third of the US track and field team had used steroids at the pre-Olympic training camp before the Mexico City Games in 1968 [6 ]. With the successful introduction of an RIA screen for anabolic steroids, [10 ] and a GC-MS method for confirmatory purposes [11 ], a trial test was introduced at the Commonwealth Games in New Zealand in February 1974, targeting the orally active alkylated AAS. Of 55 samples, 9 failed the screen and 7 samples were confirmed to be positive. In April 1974, the IOC Medical Commission included anabolic steroids as a banned class of compounds. Since then, the number of samples tested has grown to .90 000 annually, the tests have evolved, and so has the sophistication of doping. Ironically, the projected clinical usefulness of these hormones in reversing the catabolic state of patients, such as those with severe burns or wasting diseases, has not been realized. Consequently, many anabolic steroids have been withdrawn as licensed products in numerous countries, but a surplus of these steroids remains on the world market. AAS continue to be used as doping agents, despite a previous abundance of scientific literature supporting a lack of effect in intact men. For example, the extensive review of the literature by Ryan in 1976 [12 ] found a substantial body of evidence that these drugs do not contribute to muscle size and strength in healthy young men. More recent papers suggested that gains are possible if certain criteria are satisfied [13–15]. The new study by Bhasin et al. [16 ], using the advanced technique of magnetic resonance imaging [17 ], shows that administration of supraphysiological doses of T causes a significant increase in muscle mass in comparison with controls and that the effect of exercise is additive. This observation, combined with a significant increase in muscle strength, is powerful evidence and demonstrates that the athletes’ beliefs that AAS are effective were well founded. The anabolic/anti-catabolic actions of androgens are discussed by Wu [2 ], who also points out that the orally active 17-alkylated steroids are potentially the most toxic. In these proceedings, Franke and Berendonk [1 ] describe several cases of liver dysfunction and severe damage from 17-alkylated steroids. In comparison, T is a much less harmful alternative, despite its androgenic properties. Bhasin and Bremner [18 ], in their review on the emerging issues in androgen replacement therapy, note that androEditorial