Testosterone Effects On Fat Metabolism

Percent body fat is increased in hypogonadal men (76). Induction of androgen deficiency in healthy men by administration of a GnRH agonist leads to an increase in fat mass (47). Some studies of young, hypogonadal men have reported a decrease in fat mass with testosterone replacement (46,76), whereas others (77,78) found no change. In contrast, long-term studies of testosterone supplementation of older men are consistent in demonstrating a significant decrease in fat mass (79). Epidemiological studies (80,81) have found lower serum testosterone levels in middle-aged men with visceral obesity. Serum testosterone levels correlate inversely with visceral fat area and directly with plasma high-density lipoprotein (HDL) levels. Testosterone replacement of middle-aged men with visceral obesity improved insulin sensitivity and decreased blood glucose and blood pressure (82). Testosterone is an important determinant of regional fat distribution and metabolism in men (82). In our dose-response study of healthy, young men, we found testosterone dose and concentrations to be inversely related to whole body fat mass. Lower doses of testosterone that reduced serum testosterone concentrations below baseline were associated with gains

Fig. 3. Change in muscle fiber cross-sectional area in the vastus lateralis muscle of healthy, young men treated with a long-acting gonadotropin-releasing hormone agonist and graded doses of testosterone enanthate. The doses of testosterone enanthate are shown on the X-axis. Data are mean +/-SEM. (Reproduced from of ref. 84.)

in fat mass, whereas higher doses were associated with a dose-dependent decrease in fat mass. Loss of fat mass at higher doses was distributed evenly between the abdomen and trunk. Similarly, loss of fat mass was proportionate in the superficial subcutaneous compartment and the deep intermuscular compartments of the thigh. Grinspoon (61) also reported that administration of a supraphysiologic dose of testosterone is associated with loss of intermuscular fat mass in HIV-infected men. It has been hypothesized that testosterone supplementation might be beneficial in HIV-infected men with the fat-redistribution syndromes; this hypothesis is being investigated in ongoing studies.

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