Evidence for an adrenal origin of plasma estrogens in alcoholic men

Alcoholic men have high plasma-estrone concentrations but it is not known whether these are of gonadal or adrenal origin. To answer this question, we measured plasma concentrations of testosterone, androstenedione, estradiol, estrone, and cortisol in 11 alcoholic men during sequential gonadal and adrenal suppression and stimulation. Basal testosterone in the 11 alcoholic men studied did not differ from that of the 22 age-sex matched controls. It declined 75% with gonadal suppression (fluoxymesterone 80 mg/day), remained unchanged with added adrenal suppression (dexamethasone 8 mg/day), and returned to normal with gonadal stimulation (human chorionic gonadotropin 5000 U/day). Basal estradiol levels in the alcoholic men also were normal and responded to suppression and stimulation in a manner that mirrored the testosterone responses. Basal estrone in the alcoholic men was double control values (p<0.05), declined 40% in response to gonadal suppression rose and fell an additional 75% in response to adrenal suppression. While estrone doubled in response to gonadal stimulation, it rose threefold more in response to adrenal stimulation (adrenocorticotropic hormone 80 U/day). Basal androstenedione was normal and responded as expected to manipulation of gonadal and adrenal function. Based upon these responses to sequential gonadal and adrenal suppression and stimulation in alcoholic men we propose that in alcoholic men: (1) Plasma testosterone is of gonadal origin and the low concentrations observed are principally due to gonadal failure; (2) Estradiol is of gonadal origin and normal levels observed are maintained by more efficient formation from the decreased testosterone available, and (3) Estrone is partially of gonadal but chiefly of adrenal origin. These results are consistent with the hypothesis that in alcoholics with liver disease and portosystemic shunts that excessive conversion of androstenedione to estrone occurs at extrahepatic peripheral sites.