Relationship between biological sex and the endocrine stress response following a binge-like dose of alcohol

Abstract

Background: Rates of heavy drinking in the United States are rising faster in young women than in men. When "binged" rapidly, larger amounts of alcohol may activate the sexually dimorphic, limbic-hypothalamic-pituitary-adrenal (LHPA) stress axis. We examined plasma adrenocorticotropic hormone (ACTH) and cortisol responses to high-dose alcohol in the lab to determine whether social drinkers exhibited sex-specific stress responses when intoxicated. Given that one-third of young women use hormonal contraceptives (HC), which also might affect stress hormone release, we explored in a post-hoc fashion whether HC use related to LHPA responsivity among women.

Methods: Fifty-one participants (M age = 22.5 ± 1.3 years, 53% women) consumed alcohol (M = 54.7 ± 11.5 gm, sex-adjusted) in a 20% by volume solution over 10 min at 0900 h. Breath alcohol concentration (BrAC), blood pressure, and heart rate readings were obtained serially. Blood samples were obtained at baseline and every 30 min for up to 4 h postconsumption. Repeated measures ANCOVA and area-under-the-curve models tested sex effects in hormones.

Results: Despite the sexes having nearly overlapping BrACs (peak = 0.12 gm/dL at 60-min postconsumption) throughout the lab session, men exhibited a significantly elevated plasma ACTH (sex-by-time effect, p = 0.023) and cortisol (p = 0.030) response to high-dose alcohol compared with women. Among the 27 women, a post hoc exploratory analysis found that use of combination (ethinyl estradiol + progestin) oral contraceptive pills (N = 7) was associated with higher baseline and postconsumption levels of cortisol compared with naturally cycling women (N = 11) and women (N = 9) using long-acting reversible contraceptives. However, removing those participants from the analysis did not change the sex-specific results.

Conclusions: A person's biological sex relates to the endocrine response to a binge-like drinking episode. Sex differences in LHPA axis reactivity to higher doses of alcohol might influence women's and men's proclivity to develop neuroendocrine tolerance when imbibing the drug more chronically.

Keywords: ACTH and cortisol; binge drinking; endocrine stress response; sex differences; stress reactivity.