Several regulatory concerns have hindered development of
androgens as anabolic
therapies, despite unequivocal evidence that
testosterone supplementation increases muscle mass and strength in men; it induces
hypertrophy of type I and II muscle fibers, and increases myonuclear and satellite cell number.
Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, by facilitating association of
androgen receptors with
beta-catenin and activating
T-cell factor 4. Meta-analyses indicate that
testosterone supplementation increases fat-free mass and muscle strength in HIV-positive men with
weight loss,
glucocorticoid-treated men, and older men with low or low-normal
testosterone levels. The effects of
testosterone on physical function and outcomes important to patients have not, however, been studied. In older men, increased hematocrit and increased risk of prostate biopsy and detection of prostate events are the most frequent,
testosterone-related adverse events. Concerns about long-term risks have restrained enthusiasm for
testosterone use as anabolic
therapy. Selective
androgen-receptor modulators that are preferentially anabolic and that spare the prostate hold promise as anabolic
therapies. We need more studies to determine whether
testosterone or selective
androgen-receptor modulators can induce meaningful improvements in physical function and patient-important outcomes in patients with physical dysfunction associated with
chronic illness or aging.