Rocca Walter A, Grossardt Brandon R, Shuster Lynne T
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN, USA; Department of Neurology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.
Mol Cell Endocrinol. 2014 May 25;389(1-2):7-12. doi: 10.1016/j.mce.2014.01.020. Epub 2014 Feb 5.
Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age, type of menopause (natural versus induced), or stage of menopause (early versus late), consistent with the timing hypothesis. Three studies have now compared women who underwent bilateral oophorectomy before menopause with referent women and consistently showed an increased risk of cognitive decline and dementia. These studies suggest a sizeable neuroprotective effect of estrogen naturally produced by the ovaries before age 50 years. In this article, we focus on neuroprotection as related to cognitive decline and dementia. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, the clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. Three observational studies have now formally tested the timing hypothesis, and showed that the neuroprotective or harmful effects of estrogen depend on age at the time of initiation of treatment and on stage of menopause. Therefore, women who undergo bilateral oophorectomy before the onset of menopause or women who experience premature or early natural menopause should be considered for hormonal treatment until the average age of natural menopause (around age 50 years). Recommendations for the use of ET by women who experience natural menopause at typical ages remain less certain, and more research is needed.
目前的证据表明，根据年龄、绝经类型（自然绝经与人工绝经）或绝经阶段（早期与晚期），雌激素对大脑可能具有有益、中性或有害的影响，这与时机假说一致。现在有三项研究比较了绝经前接受双侧卵巢切除术的女性与对照女性，一致显示认知能力下降和痴呆的风险增加。这些研究表明，50岁之前卵巢自然产生的雌激素具有相当大的神经保护作用。在本文中，我们关注与认知能力下降和痴呆相关的神经保护作用。几项病例对照研究和队列研究也显示，绝经后早期（最常见于50 - 60岁）接受雌激素治疗（ET）的女性具有神经保护作用。这些观察性研究中的大多数女性经历了自然绝经，并接受治疗以缓解绝经症状。然而，妇女健康倡议组织的临床试验表明，在绝经后期（65 - 79岁）开始单独使用ET或与孕激素联合使用ET的女性，无论绝经类型如何，患痴呆和认知能力下降的风险都会增加。现在有三项观察性研究正式检验了时机假说，结果表明雌激素的神经保护或有害作用取决于开始治疗时的年龄和绝经阶段。因此，在绝经开始前接受双侧卵巢切除术的女性或经历过早或早期自然绝经的女性，应考虑进行激素治疗，直至达到自然绝经的平均年龄（约50岁）。对于在典型年龄经历自然绝经的女性使用ET的建议仍不太确定，需要更多的研究。
