The metabolic syndrome is a common metabolic disorder which is closely linked to a generalized metabolic disorder called insulin resistance in which the normal actions of insulin are impaired. The syndrome is associated with increased risk for type II diabetes mellitus and cardiovascular disease, and its pathogenesis is multifactorial. Obesity and sedentary lifestyle are major components; however, recently it has been demonstrated that in males reduction of endogenous sex hormone levels is importantly linked to the occurrence of the metabolic syndrome. Interestingly, obesity and type II diabetes are frequently associated with low testosterone levels in men, and few studies have addressed the issue of the mechanism of this reduction. The decline of testosterone levels occurring in obese or diabetic men, as well as in older males, usually it is not accompanied by a compensatory rise in gonadotrophins; for this reason, in a rather simplistic way, the hypogonadism of diabetics has been often labeled as exclusively hypogonadotropic. However, there is a number of publications showing that this phenomenon has a combined etiology, central and peripheral. More important, in obese and insulin resistant subjects the frequently described hypogonadism may have a prevalent peripheral origin. It has been shown that aging is associated with a defective LH signal transduction in Leydig cells, and it has been demonstrated that in male obesity the defect in Leydig cells testosterone production correlates with insulin resistance and it is not the consequence of a chronic alteration in the hypothalamic-pituitary function. Finally, we found that in adult obese men, Leydig cell output is progressively reduced with increasing adiposity, and that adipocyte derived products, such as leptin, are likely to be involved. Since higher testosterone is associated with a higher insulin sensitivity and a reduced risk of the metabolic syndrome, it is conceivable to hypothesize that testosterone may exert a protective role in the development of the metabolic syndrome and insulin resistance in aging and obese men.
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