Testosterone effects on fat metabolism

Percent body fat is higher in hypogonadal men in comparison to eugonadal controls (Katznelson etal. 1998). Induction of androgen deficiency in healthy men by administration of a GnRH agonist leads to an increase in fat mass (Mauras et al. 1998). Some studies of young, hypogonadal men have reported a decrease in fat mass with testosterone replacement therapy (Brodsky etal. 1996; Katznelson etal. 1996; Snyder etal. 2000) while others (Bhasin etal. 1997; Wang etal. 1996) found no change. In contrast, long-term studies of testosterone supplementation of older men have consistently demonstrated a decrease in fat mass (Kenny etal. 2001; Snyder etal. 1999; Tenover 2000). Epidemiologic studies (Khaw and Barrett-Connor 1992; Seidell etal. 1990) have shown that serum testosterone levels are lower in middle-aged men with visceral obesity. Serum testosterone levels correlate inversely with visceral fat area and directly with plasma HDL levels. Testosterone replacement of middle-aged men with visceral obesity improves insulin sensitivity, decreases blood glucose and blood pressure (Marin et al. 1992; 1996). In our dose-response studies, administration of graded doses of testosterone to men was associated with a dose-dependent decrease in fat mass (Bhasin etal. 2001). Loss of fat mass at higher doses was evenly distributed in the trunk and appendices, and in the superficial and deep compartments. Thus, there was a decrease in intra-abdominal fat as well as intermuscular fat in association with high doses of testosterone. Testosterone is an important determinant of regional fat distribution and metabolism in men (Marin etal. 1996).

8.8 Key messages

• Androgens have direct anabolic effects on the muscle. Testosterone administration to healthy, young men is associated with dose-dependent increments in fat-free mass, muscle size, and maximal voluntary strength.

• In older men with low testosterone levels, testosterone replacement increases fat-free mass and decreases fat mass. We do not know whether testosterone replacement of older men improves physical function or other health-related outcomes, and whether it reduces the risk of falls, fractures, and disability.

• Testosterone-induced increase in skeletal muscle mass is due to muscle fiber hypertrophy.

• Testosterone increases muscle mass and reduces fat mass by promoting the commitment and differentiation of mesenchymal, pluripotent stem cells into the myogenic lineage and inhibiting their differentiation into the adipogenic lineage.

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