Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: influence of age and sex

Alcohol Clin Exp Res. 2012 Feb;36(2):207-13. doi: 10.1111/j.1530-0277.2011.01600.x. Epub 2011 Jul 28.

Abstract

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 GH-IGF-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 × 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 × 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Aging / physiology*
  • Breath Tests
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology*
  • Data Interpretation, Statistical
  • Estradiol / blood
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Female
  • Gonadal Hormones / metabolism*
  • Human Growth Hormone / metabolism
  • Humans
  • Injections, Intravenous
  • Insulin-Like Growth Factor I / metabolism
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Ovary / drug effects
  • Ovary / metabolism*
  • Sex Characteristics
  • Single-Blind Method
  • Testis / drug effects
  • Testis / metabolism*
  • Testosterone / blood
  • Young Adult

Substances

  • Central Nervous System Depressants
  • Gonadal Hormones
  • Human Growth Hormone
  • Ethanol
  • Testosterone
  • Estradiol
  • Insulin-Like Growth Factor I