17β-Estradiol (estradiol or E2) is implicated as a neuroprotective factor in a variety of neurodegenerative disorders. This review focuses on the mechanisms underlying E2 neuroprotection in cerebral ischemia, as well as emerging evidence from basic science and clinical studies, which suggests that there is a "critical period" for estradiol's beneficial effect in the brain. Potential mechanisms underlying the critical period are discussed, as are the neurological consequences of long-term E2 deprivation (LTED) in animals and in humans after natural menopause or surgical menopause. We also summarize the major clinical trials concerning postmenopausal hormone therapy (HT), comparing their outcomes with respect to cardiovascular and neurological disease and discussing their relevance to the critical period hypothesis. Finally, potential caveats, controversies and future directions for the field are highlighted and discussed throughout the review.

中文翻译：

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雌激素神经保护和关键期假说

17β-雌二醇（雌二醇或 E2）是多种神经退行性疾病中的神经保护因子。本综述重点关注脑缺血中 E2 神经保护的机制，以及来自基础科学和临床研究的新证据，这些证据表明雌二醇对大脑的有益作用存在一个“关键期”。讨论了关键期的潜在机制，以及自然绝经或手术绝经后动物和人类长期 E2 剥夺 (LTED) 的神经学后果。我们还总结了有关绝经后激素治疗（HT）的主要临床试验，比较了它们在心血管和神经系统疾病方面的结果，并讨论了它们与关键期假说的相关性。最后，在整个审查过程中强调并讨论了该领域的潜在警告、争议和未来方向。