Leasure J Leigh, Van Doorn Catherine E, Nixon Kimberly
Department of Psychology, University of Houston, Houston, TX 77204-5022, United States.
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, United States.
Front Neuroendocrinol. 2025 Jul;78:101201. doi: 10.1016/j.yfrne.2025.101201. Epub 2025 Jun 4.
Aging and alcohol exert marked effects on the endocrine system - in particular the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. The aging female brain represents a unique substrate for alcohol effects, given that both the HPG and HPA undergo significant changes with aging in women, making this demographic notably different from both males and younger females. Little attention has been directed at alcohol effects in this group but changing trends in women's drinking have brought these issues to the forefront. Major gaps in our understanding of aging females include how stressors common to middle and older aged women impact alcohol consumption, and how alcohol consumption in older women impacts brain health and aging. Thus, here we review the current state of knowledge concerning the unique neuroendocrinology of aging females, their stressors and pharmacokinetic reactions to alcohol, and their interactions as causes and neurotoxic consequences of excessive alcohol drinking. We highlight the role of the neuroimmune system at the intersection of aging, alcohol and stress effects, and brain endocrine systems. We conclude that therapeutic interventions should be aimed at managing alcohol-induced neuroimmune responses and their downstream effects on vulnerable white matter. In addition, mid-life represents a window of opportunity in which to introduce strategies to limit alcohol consumption and its consequences for the aging female brain. As so little is known about how alcohol intake impacts brain health in females, let alone in aging females, we assert the need for further investigation of middle-aged and aged females in human and preclinical studies.
衰老和酒精对内分泌系统，尤其是下丘脑-垂体-性腺（HPG）轴和下丘脑-垂体-肾上腺（HPA）轴，有着显著影响。衰老的女性大脑是酒精作用的独特靶点，因为HPG轴和HPA轴在女性衰老过程中都会发生显著变化，这使得该人群与男性和年轻女性明显不同。目前很少有人关注酒精对这一群体的影响，但女性饮酒趋势的变化已将这些问题推到了前沿。我们对衰老女性的了解存在重大空白，包括中老年女性常见的压力源如何影响酒精消费，以及老年女性饮酒如何影响大脑健康和衰老。因此，在这里我们回顾了有关衰老女性独特神经内分泌学、她们的压力源和对酒精的药代动力学反应，以及它们作为过量饮酒的原因和神经毒性后果之间相互作用的现有知识。我们强调神经免疫系统在衰老、酒精和压力影响以及大脑内分泌系统交叉点上的作用。我们得出结论，治疗干预应旨在控制酒精诱导的神经免疫反应及其对易损白质的下游影响。此外，中年是引入策略以限制酒精消费及其对衰老女性大脑影响的一个机会窗口。由于我们对酒精摄入如何影响女性大脑健康知之甚少，更不用说衰老女性了，我们主张在人体和临床前研究中进一步调查中年和老年女性。
