It is well established that androgens cause nitrogen retention in the body. Androgens increase the lean body mass and muscle mass by increasing muscle protein synthesis (36). A recent study showed that testosterone treatment induces muscle fiber hypertrophy (37). Androgens administered as sublingual tablets, injections, and transdermals increased muscle mass assessed by dual-energy X-ray absorptiometry (DEXA) scans in hypogonadal men (16,17,38-40). This increase in muscle mass is observed not only in younger but also in older men with partial androgen deficiency (18,20). The increase in muscle mass was associated with increased muscle strength in both the upper and the lower limbs in younger hypogonadal men assessed by several different techniques (16,17,38-40). In older men, assessment of muscle strength is more difficult (41) and improvement in strength has not been always demonstrated (18,20). Moreover, it is not clear whether the increase in muscle strength will be functionally important in older men. The increase in muscle mass is directly related to the amount of testosterone administered and to the serum testosterone concentration. This dose-response relationship is also observed between changes in muscle strength and serum testosterone concentrations achieved (21).
Concomitant with the increases in muscle mass after androgen substitution in hypogonadal men, there are decreases in fat mass and percent fat measured by DEXA or visceral fat measured by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) scan. The decreases in fat mass have been demonstrated with injectables and transdermals but not with the sublingual testosterone (16,17,38-40), which may be related to the amount of testosterone delivered to the body. A dose-response study showed that the decrease in fat mass is inversely related to the serum testosterone level and the dose of testosterone administered (21). Decreases in fat mass are also observed in middle-aged or older men administered testosterone (18,30,42). The decrease in visceral fat observed in some studies has been suggested to result in decrease in insulin resistance. Testosterone and its esters have no significant effects on glucose metabolism and insulin sensitivity in younger men (43). In older men, whether androgen replacement has any effect on insulin resistance, and, if so, whether it acts through visceral fat decreases has not been clarified (42,43).
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