Window of Opportunity of Estrogen Therapy for Neuroprotection

从1995年到2050年，阿尔茨海默病（AD）的发病率预计将翻一番，造成毁灭性的全球负担。关于雌激素激素治疗（E/HT）对绝经后妇女认知影响的个体研究结果不一致，可能是方法学差异的结果。基于大量研究结果的积累，一些作者假设了E/HT给药提供神经保护的“关键时期”或“机会之窗”。来自动物和人类研究的综合证据证实了年轻和老年绝经后妇女对认知的不同影响。此外，最近对妇女健康倡议（WHI）数据的再分析发现，E/HT可能对心脏有益，但仅适用于较年轻的绝经后妇女。无论如何，自从世界卫生组织最初公布阴性结果以来，许多可能受益于E/HT的妇女害怕使用它。因此，需要翻译研究模型来帮助区分混淆E/HT对认知影响的变量，以便确定高危人群的最佳治疗方法。

DESCRIPTION (provided by applicant): Abstract Incidence rates of Alzheimer's disease (AD) are expected to double from 1995 to 2050 creating a devastating global burden. Findings across individual studies regarding the effects of estrogen hormone therapy (E/HT) on cognition in postmenopausal women are inconsistent, likely as the result of methodological differences. Based on the accumulation of outcomes across numerous studies, several authors have postulated a "critical period" or "window of opportunity" when E/HT administration affords neuroprotection. The differential effects on cognition in younger versus older postmenopausal women is substantiated by combined evidence from animal and human studies. In addition, recent reanalysis of Women's Health Initiative (WHI) data found possible cardiac benefits with E/HT, but only in younger postmenopausal women. Regardless, since the initial release of the WHI negative findings, many women who might benefit from E/HT fear its use. Consequently, translational research models are needed to assist in parceling out the variables that confound the effects of E/HT on cognition in order to determine the best treatment practices for at risk populations. PUBLIC HEALTH RELEVANCE: Findings across numerous studies provide evidence that estrogen hormone therapy (E/HT) may be neuroprotective for at least some women when used in perimenopause or early menopause, but not in late menopause. Translational research models are needed to elucidate this "window of opportunity" in order to determine best treatment practices and populations who may or may not benefit from estrogen therapy. Given the rise in Alzheimer's disease prevalence, development of treatment protocols that could prevent or slow down disease progression are imperative.