The anabolic effects of androgens have generated enormous controversy for more than 60 yr, in part because of flaws in the design of studies published before the 1990s. Many of the earlier studies were neither randomized nor blinded, and the doses of androgenic steroids used were relatively small. Exercise stimulus and protein and energy intakes were not standardized in many studies. Some of the studies even included competitive athletes, and failure to control exercise regimens made it difficult to separate the effects of androgens from those of resistance exercise training.
However, several recent studies have demonstrated unequivocally that testosterone supplementation in androgen-deficient men increases fat-free mass, muscle size, and maximal voluntary strength in numerous clinical paradigms. Some, but not all, testosterone replacement studies have reported loss of fat mass during testosterone replacement. Brodsky et al. (46) reported that testosterone replacement increases fractional muscle protein synthesis.
Conversely, lowering of serum testosterone concentrations by administration of a long-acting GnRH agonist is associated with a decline in fat-free mass and decreased muscle protein synthesis (47). Furthermore, fat-free mass is lower and fat mass is higher in androgen-deficient men when compared to age-matched controls. Several epidemiological studies are in agreement that low non-sex hormone-binding globulin (SHBG) (bioavailable) testosterone levels correlate with lower whole body and appendicular fat-free mass and strength of knee flexion and extension in older men.
Supraphysiological doses of testosterone, when administered to eugonadal men, further increase fat-free mass, muscle size, and strength, when confounding variables, such as energy and protein intake and exercise stimulus, are controlled (48-50). Testosterone effects on the muscle are related to testosterone dose and concentrations (51). Resistance exercise training augments the anabolic response to androgen administration; thus, the combination of administration of testosterone and strength training is associated with greater increments in fat-free mass and muscle strength than either intervention alone (52,53).
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