Abstract

Total and free testosterone concentrations decline progressively with advancing age because of defects at all levels of the hypothalamic-pituitary-testicular axis. Low total and bioavailable testosterone levels have been associated with decreased skeletal muscle mass, muscle strength, physical function, bone mineral density, and fracture risk, although these associations are weak. The risks and health benefits of long-term testosterone remain poorly understood. Physiologic testosterone replacement of young, androgen-deficient men and older men with low testosterone levels is associated with an increase in fat-free mass, grip strength, and fractional muscle protein synthesis, but we do not know whether testosterone replacement improves quadriceps strength, power, muscle fatigability, and physical function in older men, and whether it can reduce the risk of disability and falls. Testosterone replacement increases vertebral bone mineral density in young hypogonadal men and older men with low testosterone levels, but we do not know whether testosterone reduces fracture risk. Concerns about the potential adverse effects of testosterone on the prostate have encouraged the development of selective androgen receptor modulators that increase muscle mass while sparing the prostate.