Window of Opportunity of Estrogen Therapy for Neuroprotection

描述(由申请人提供)：阿尔茨海默病(AD)的发病率预计将从1995年到2050年翻一番，造成毁灭性的全球负担。关于雌激素治疗(E/HT)对绝经后妇女认知的影响的个别研究的结果是不一致的，可能是由于方法上的差异。根据大量研究结果的积累，几位作者假设了E/HT治疗提供神经保护的“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绝经后年轻女性和老年女性对认知的不同影响。此外，最近对妇女健康倡议(WHI)数据的重新分析发现，E/HT可能对心脏有益，但仅适用于更年轻的绝经后妇女。无论如何，自从WHI阴性结果最初公布以来，许多可能从E/HT中受益的女性担心它的使用。因此，需要转换研究模型来帮助确定E/HT对认知的影响的变量，以便确定高危人群的最佳治疗实践。 公共卫生相关性：大量研究的结果表明，雌激素疗法(E/HT)在围绝经期或更年期早期使用时可能对至少一些女性具有神经保护作用，但在更年期晚期则不起作用。需要转换研究模型来阐明这一“机会之窗”，以确定最佳治疗实践和可能受益于或可能不受益于雌激素治疗的人群。鉴于阿尔茨海默病患病率的上升，开发能够预防或减缓疾病进展的治疗方案势在必行。

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.