Endocrine Abstracts

Epidemiologic studies have associated low testosterone levels with increased cardiovascular mortality in men, the mechanism of which is unclear. However, low testosterone levels have been linked to the development of cardiovascular risk factors including metabolic syndrome, regardless of the definition employed. This relationship has been observed in epidemiologic studies of community-dwelling men as well as in men with prostate cancer treated with androgen-deprivation therapy.

Insulin resistance plays a key role in the development of metabolic syndrome and testosterone levels are positively correlated with insulin sensitivity in men. It is likely that, at least part of, the relationship between low testosterone and metabolic syndrome is explained by the increase in central body fat associated with hypogonadism due to increased lipoprotein lipase activity, increased triglyceride uptake and decreased lipolysis. However, the fact that the relationship between low testosterone levels and metabolic syndrome is strong even in lean individuals, and that short-term induction of hypogonadism also adversely effects insulin sensitivity, suggests that factors other than body composition may also be implicated. Other potential mechanisms by which low testosterone levels may promote insulin resistance include an increase in the level of pro-inflammatory cytokines and the induction of mitochondrial dysfunction.

To date, limited data are available on the impact of testosterone supplementation on metabolic syndrome. A non placebo-controlled study of hypogonadal men showed a significant reduction in waist circumference, total cholesterol and triglycerides after 12 months testosterone therapy. However, the demonstration that. increasing insulin resistance is associated with decreased testosterone secretion from Leydig cells and that weight loss increases testosterone levels in obese men suggests that the relationship between low testosterone levels and metabolic syndrome, is in fact, bidirectional.

Thus, larger placebo-controlled trials are required to establish the causal nature of the testosterone deficiency associated with metabolic syndrome in men and the potential metabolic benefits of androgen replacement therapy.