Pharmacodynamic Effects of Intravenous Alcohol on Hepatic and Gonadal Hormones: Influence of Age and Sex

Background: Growth hormone (GH)insulin-like growth factor-1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GHIGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Methods: Forty-eight healthy volunteers (24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups) underwent a 2-session single-blinded study. Subjects received in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically based pharmacokinetic model, to maintain a steady-state ("clamped") exposure of 50 mg% or saline for 3 hours in separate sessions. Blood samples collected at baseline and postinfusion in each session were assayed for levels of GH, IGF-1, free testosterone, and estradiol. Results: Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment x baseline interaction (p < 0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in men. On the other hand, change in estradiol showed a significant treatment x sex interaction (p = 0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in women. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p < 0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p = 0.046) indicating that men had greater changes in GH across treatment compared with women. Conclusions: Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in women.