Historical aspects of the anabolic steroid controversy

Soon after the biochemical synthesis of testosterone, several groups investigated the anabolic effects of testosterone in animal models. During the 1930s, Kochakian

(1935) first described the nitrogen-retaining properties of urinary androgens in the castrate dog. He recorded similar effects of androgens in the castrated male rat and found that the androgen stimulation resulted in dose-related increases in nitrogen retention and body weight (Kochakian 1935; 1937; 1950).

Shortly after the initial animal studies, Kenyon etal. (1940) studied the effects of testosterone propionate in eunuchoidal men, and eugonadal men andwomen. During androgen treatment, urinary nitrogen excretion diminished, with the greatest magnitude of effects observed in eunuchoidal men. Kenyon concluded presciently that "The... protein estimated as retained by these subjects is not accounted for by increases in the bulk of genital tissues and represents deposit of new material elsewhere in the body" (Kenyon 1940). These observations, combined with the results of the animal studies, allowed the early recognition of the anabolic effects of andro-gens. It is notable that Kenyon and others were not able to demonstrate sustained increases in nitrogen retention with testosterone supplementation in eugonadal men, an observation that sparked considerable skepticism for the next fifty years about the anabolic effects of supraphysiological doses of androgens in eugonadal men.

Although the use of performance-enhancing products dates back to antiquity, anabolic steroids have emerged as the most prevalent drugs of abuse among athletes in recent decades (Dawson 2001). Although the Russian power lifters were perhaps the first to abuse anabolic steroids in the early 1950s, this practice spread quickly to athletes in other countries. The systematic use of anabolic steroids by athletes in the former German Democratic Republic was an extreme example of state-sponsored malpractice; however, the abuse of performance-enhancing drugs is not limited to any one nation. Athletes and recreational bodybuilders who abuse androgenic steroids believe that these compounds increase muscle mass and performance and that higher doses of androgens produce greater effects on the muscle than lower doses (Wilson 1988). Hence, they take large doses and abuse multiple steroids simultaneously in a practice called stacking (Dawson 2001; Wilson 1988). Until a few years ago, the academic community was skeptical of these claims, and interpreted the available data to imply that only replacement doses of androgens in castrated males increased nitrogen retention, and that supraphysiologic doses of androgens did not further increase muscle mass and strength when given to eugonadal men. Considerable debate raged in the academic community for five decades on whether androgenic steroids had anabolic effects on the muscle, due in part to the shortcomings of previous studies; several reviews (Bardin 1996; Wilson 1988) have discussed these study design issues. Many of the previous studies that examined the effects of androgenic steroids were neither blinded nor randomized. Some studies included competitive athletes, whose desire to win might preclude compliance with a standardized regimen of diet and exercise. Nutritional intake was not controlled in many of the studies; changes in energy and protein intake might have had independent effects on nitrogen balance. Exercise stimulus was not standardized and, in some studies, the participants were allowed to exercise ad libitum. Therefore, the effects of androgen administration could not be separated from the effects of resistance exercise training (Bhasin et al. 2001a). Most of the studies used relatively small doses of androgenic steroids (Bhasin etal. 2003a), in contrast, athletes use much larger doses of androgenic steroids. Not surprisingly, the results of these studies were inconclusive. However, studies published in the last decade by a number of groups have established that testosterone supplementation increases muscle mass and maximal voluntary strength (Bhasin et al. 1996; 1997; Brodsky etal. 1996; Katznelson etal. 1996; Snyder and Laurence 1980; Snyder etal. 2000; Wang etal. 1996; 2000).

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