Obesity and androgens: facts and perspectives

This review discusses androgen status in male and female obesity, according to their specific phenotype, and the main mechanisms responsible.

Published data in the literature of the last 20 years represented the basis of most of the data and concepts incorporated in the review.

Obesity is associated with profound alterations in androgen secretion, transport, metabolism, and action, according to a dichotomous behavior depending on sex. Obese men are characterized by a progressive decrease of testosterone levels with increasing body weight, whereas obese women, particularly those with the abdominal phenotype, tend to develop a condition of functional hyperandrogenism. Reduced sex hormone-binding globulin synthesis and circulating blood levels represent the sole common mechanism which is responsible in both sexes. Among other still partially undefined factors, mechanisms potentially responsible for the sex dichotomy in androgen levels involve specific alterations of gonadotropin secretion, estrogens, the hypothalamic-pituitary-adrenal axis, leptin, androgen receptors, specific steroidogenic enzymes in the peripheral tissues, and, possibly, ghrelin. In both sexes, androgens play an important role in determining the sex-dependent pattern of body fat distribution. Moreover there are theoretical possibilities that low testosterone in men and high free testosterone fraction in women may play a role in the development of the metabolic syndrome. This is exemplified by the well defined association between obesity and other features of the metabolic syndrome in women with polycystic ovary syndrome and in hypogonadal men. The effects of androgen and antiandrogens in obese men and women also represent arguments in favor of this association.

Given the fundamental role of sex hormones in the regulation of body composition, fuel homeostasis, and reproduction in humans, more emphasis should be placed on the potential role of androgen dysregulation in the pathophysiology of different obesity phenotypes and the metabolic syndrome.