EFFECTS OF TESTOSTERONE REPLACEMENT ON MUSCLE MASS AND MUSCLE PROTEIN-SYNTHESIS IN HYPOGONADAL MEN - A CLINICAL RESEARCH-CENTER STUDY

Testosterone replacement in hypogonadism has long been known to promot e nitrogen retention and increase body density, but the mechanisms of nitrogen retention and body composition changes are poorly defined. We measured body composition and muscle protein synthesis in five hypogo nadal men before and 6 months after initiating testosterone replacemen t. Body composition was examined using dual energy x-ray absorptiometr y. Muscle mass was estimated both by excretion of creatinine on a meat -free diet and from appen dicular mass measured using dual energy x-ra y absorptiometry. Muscle protein synthesis was assessed by measuring t he increment of [C-13]leucine in mixed muscle protein and myosin heavy chain during a continuous infusion of L-[1-C-13]leucine. In all subje cts there was an increase in fat-free mass (average, 15%; range, 10-22 %; P = 0.02) and a decrease in fat mass (-11%; range, -0.4% to -22.0%; P = 0.03). Muscle mass also increased in everybody (mean, 20%; range, 11-32%; P = 0.04) such that 65% of the increase in fat-free mass coul d be attributed to accretion of muscle. The accumulation of muscle was associated with a 56% (P = 0.015) increase in the fractional synthesi s rate of mixed skeletal muscle proteins and a trend toward a similar increase in the fractional synthesis rate of myosin heavy chain (46%; P = 0.098). We conclude that testosterone replacement in hypogonadal m en enhanced skeletal muscle mass by stimulating the muscle protein syn thesis rate.