Obesity in men: the hypogonadal-estrogen receptor relationship and its effect on glucose homeostasis

Aromatase is important in men's health, obesity, the metabolic syndrome, type 2 diabetes and aging. In males with increasing obesity there is increased aromatase activity, which irreversibly converts testosterone to estradiol resulting in decreased testosterone and elevated estrogen levels. Since androgens reduce the expression of ER beta activity, decreased testosterone levels release the normally suppressed ER beta expression and results in the down regulation of GLUT4 with resultant insulin resistance. The increased estradiol concentrations influence both of the estrogen receptors, but specifically intensify the metabolic effects of ER beta because of its released suppression, a consequence of diminished testosterone concentrations. These dual actions then combine to amplify the mechanisms that lead to disordered glucose homeostasis and insulin resistance under these conditions. An appreciation of the relationships between the hormonal products of aromatase activity and their direct effects on the estrogen receptors focuses on potential innovative therapeutic interventions. These include aromatase inhibitors, which correct the dual consequences of hypotestosteronemia and hyperestrogenemia and eventually ER beta antagonists when they become available.