title: Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: influence of age and sex.
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.
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-1540, USA.
authors.forename: Vatsalya
authors.initials: V
authors.lastname: Vatsalya
authors.forename: Julnar E
authors.initials: JE
authors.lastname: Issa
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommer
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Ramchandani
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001944:Breath Tests; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D004958:Estradiol / Q000097:blood; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D042341:Gonadal Hormones / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics; D016037:Single-Blind Method; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D042341:Gonadal Hormones; D019382:Human Growth Hormone; D000431:Ethanol; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I