There is a high prevalence of low testosterone concentrations in HIV-infected individuals resulting from defects at all levels of the hypothalamic-pituitary-gonadal axis. Both hypogonadotropic and hypergonadotropic hypogonadism have been described, the former being more prevalent. Low testosterone concentrations are associated with adverse disease outcomes, including weight loss, disease progression, and decreased muscle mass and exercise capacity. Physiologic testosterone replacement increases fat-free mass and maximal voluntary strength in HIV-infected men with low testosterone concentrations. Testosterone administration also decreases whole body and visceral fat mass in middle-aged men with low normal testosterone concentrations. The effects of testosterone supplementation in HIV-associated fat redistribution syndromes are being investigated. Testosterone increases muscle mass and decreases fat mass by promoting the differentiation of pluipotent precursor cells into the myogenic lineage and inhibiting their differentiation into the adipogenic lineage. Long-term, adequately powered, randomized, placebo-controlled, studies are needed to determine the effects of testosterone replacement on health-related outcomes, such as cardiovascular event rates, health-related quality of life, and disability.

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