Anthenelli Robert M, Miles Mary J, Hauger Richard, Schuckit Marc A, McKenna Benjamin S
Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California, USA.
Center of Excellence for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, California, USA.
Alcohol Clin Exp Res (Hoboken). 2025 Aug 1. doi: 10.1111/acer.70094.
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.
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.
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.
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.
美国年轻女性中重度饮酒率的上升速度比男性更快。当快速“暴饮”时，大量酒精可能会激活具有性别差异的边缘-下丘脑-垂体-肾上腺（LHPA）应激轴。我们在实验室中检测了血浆促肾上腺皮质激素（ACTH）和皮质醇对高剂量酒精的反应，以确定社交饮酒者在醉酒时是否表现出性别特异性应激反应。鉴于三分之一的年轻女性使用激素避孕药（HC），这也可能影响应激激素的释放，我们以事后分析的方式探讨了HC的使用与女性LHPA反应性之间的关系。
51名参与者（平均年龄=22.5±1.3岁，53%为女性）于上午9点在10分钟内饮用了酒精（平均量=54.7±11.5克，经性别调整），酒精浓度为20%（体积分数）。连续获取呼气酒精浓度（BrAC）、血压和心率读数。在基线时以及饮酒后长达4小时内，每30分钟采集一次血样。重复测量协方差分析和曲线下面积模型用于测试激素的性别效应。
尽管在整个实验室测试过程中，男女的BrAC几乎重叠（饮用后60分钟时峰值=0.12克/分升），但与女性相比，男性对高剂量酒精的血浆ACTH反应（性别×时间效应，p=0.023）和皮质醇反应（p=0.030）显著升高。在27名女性中，事后探索性分析发现，与自然月经周期的女性（n=11）和使用长效可逆避孕药的女性（n=9）相比，服用复方（炔雌醇+孕激素）口服避孕药的女性（n=7）的皮质醇基线水平和饮酒后水平更高。然而，将这些参与者从分析中剔除并未改变性别特异性结果。
一个人的生理性别与类似暴饮的饮酒事件的内分泌反应有关。LHPA轴对更高剂量酒精的反应性存在性别差异，这可能会影响女性和男性在长期饮酒时产生神经内分泌耐受性的倾向。
