Hormonal Abnormalities in Obesity

ABSTRACT We have found a number of interesting hormonal abnormalities in obese men and women: 1) Obese women have normal levels of estrone, total estradiol, and total testosterone, but as a consequence of their subnormal levels of SHBG, their levels of free estradiol and free testosterone are significantly elevated. 2) Massive weight loss in obese women (to still elevated weight) results in normalization of the previously elevated free estradiol and free testosterone. 3) Obese women have normal plasma DHEA levels, but a significant, age‐invariant decrease of the plasma DHEA/T ratio, which could be due to increased tissue activity of 3β‐hydroxysteroid dehydrogenase. 4) Massive weight loss produces an age‐dependent effect on DHEA levels in obese women: the levels increase to supranormal values in women around age 20, with diminishing increases at higher premenopausal ages and no increase at all at perimenopausal age. 5) Obese men have elevated levels of estrone and both free and total estradiol, and subnormal levels of free and total testosterone and of FSH; all these abnormalities are proportional to the degree of obesity. They also have relatively subnormal LH levels, i.e. normal in the face of hypotestosteronemia. The combination of these findings represents a state of mild hypogonadotropic hypogonadism (HHG), which we believe to be induced by the hyperestrogenemia. 6) Normalization of the estrogen levels of obese men, by suppression of adrenocortical secretion of aromatase substrates or by inhibition of aromatase, tends to normalize the HHG. 7) Massive weight loss in obese men normalizes their HHG without any decrease in plasma estrogen levels. This suggests that weight loss in obese men results in diminished sensitivity of the GnRH‐gonadotropin secretory mechanism to suppression by a given concentration of estrogen. 1987 Association for the Publication of the Journal of Internal Medicine