Department of Neurosurgery, West Virginia University, Morgantown, West Virginia, USA.
Am J Pathol. 2011 Jun;178(6):2450-60. doi: 10.1016/j.ajpath.2011.01.057.
In 2000, approximately 10 million women were receiving hormone replacement therapy (HRT) for alleviation of menopausal symptoms. A number of prior animal studies suggested that HRT may be neuroprotective and cardioprotective. Then, in 2003, reports from the Women's Health Initiative (WHI) indicated that long-term estrogen/progestin supplementation led to increased incidence of stroke. A second branch of the WHI in women with prior hysterectomy found an even stronger correlation between estrogen supplementation alone and stroke incidence. Follow-up analyses of the data, as well as data from other smaller clinical trials, have also demonstrated increased stroke severity in women receiving HRT or estrogen alone. This review examines the studies indicating that estrogen is neuroprotectant in animal models and explores potential reasons why this may not be true in postmenopausal women. Specifically, age-related differences in estrogen receptors and estrogenic actions in the brain are discussed, with the conclusion that animal models of disease must closely mimic human disease to produce clinically relevant results.
2000 年，约有 1000 万女性接受激素替代疗法（HRT）以缓解更年期症状。一些先前的动物研究表明，HRT 可能具有神经保护和心脏保护作用。然后，在 2003 年，妇女健康倡议（WHI）的报告表明，长期雌激素/孕激素补充剂会导致中风发病率增加。WHI 的第二个分支针对已行子宫切除术的女性，发现单独补充雌激素与中风发病率之间的相关性更强。对数据的后续分析以及其他较小临床试验的数据也表明，接受 HRT 或单独雌激素治疗的女性中风严重程度更高。这篇综述探讨了表明雌激素在动物模型中具有神经保护作用的研究，并探讨了为什么这在绝经后女性中可能不成立的潜在原因。具体而言，讨论了与年龄相关的脑内雌激素受体和雌激素作用的差异，并得出结论，疾病的动物模型必须紧密模拟人类疾病才能产生临床相关的结果。
