McCarrey Anna C, Resnick Susan M
Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore, MD, 21224, USA.
Horm Behav. 2015 Aug;74:167-72. doi: 10.1016/j.yhbeh.2015.04.018. Epub 2015 Apr 30.
This article is part of a Special Issue "Estradiol and cognition". Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the 'critical window hypothesis', which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments.
本文是《雌二醇与认知》特刊的一部分。在2002年妇女健康倡议（WHI）的研究结果发表之前，含雌激素的激素疗法（HT）被用于预防与年龄相关的疾病，尤其是心血管疾病，并治疗潮热和睡眠紊乱等更年期症状。一些针对中年及老年女性的HT观察性研究表明，HT可能对认知功能也有益处，但随机临床试验在健康和认知结果方面得出了不一致的结论。本综述重点关注激素对自然绝经女性以及手术诱导绝经女性的认知和痴呆风险的影响，并强调了大规模WHI记忆研究（WHIMS）的结果，与预期相反，该研究表明，随机接受HT的绝经后老年女性与接受安慰剂的女性相比，痴呆风险增加且认知结果更差。我们考虑了“关键窗口期假说”，该假说认为，绝经后不久可能存在一个机会窗口，在此期间雌激素治疗最为有效。此外，我们强调了新出现的证据，即HT对认知的潜在不良影响在有其他健康风险的女性中最为明显，比如整体认知水平较低或患有糖尿病的女性。最后，我们指出了对未来研究和临床治疗的启示。
