Departments of Health Research and Policy (Epidemiology) and Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20290-5. doi: 10.1073/pnas.1312353110. Epub 2013 Nov 25.
Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (<6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.
绝经后激素环境的变化可能会影响与认知、认知老化和情绪相关的神经过程,但研究结果并不一致。特别是,雌二醇对认知的影响可能随绝经后时间的变化而变化,但这一预测尚未通过血清激素浓度的直接评估来验证。我们研究了 643 名未接受激素治疗的健康绝经后妇女,她们被分为绝经早期(<6 年)和绝经晚期(>10 年)组。女性接受了全面的神经心理学测试,并接受了流行病学研究抑郁量表的评估。她们提供了血清样本以进行游离雌二醇、雌酮、孕酮、游离睾酮和性激素结合球蛋白的测量。认知结果是经过标准化的口头情节记忆、执行功能和总体认知的综合指标。分别对每种激素进行了协变量调整后的线性回归分析,并在调整其他激素水平后进行了分析。内源性性激素水平与认知综合指标无关,但性激素结合球蛋白与口头记忆呈正相关。早期和晚期组的结果没有显著差异,尽管孕激素浓度与早期组女性的口头记忆和总体认知呈显著正相关。激素浓度与情绪没有显著相关。结果不支持这样的假设,即绝经时间的临近会改变内源性雌二醇水平与口头记忆、执行功能或总体认知之间的关系。绝经后内源性性激素水平的生理变化与这些认知或情绪方面没有显著关系;孕激素和性激素结合球蛋白的正相关关系值得进一步研究。