From the Department of Nuclear Medicine and Radiobiology (S.C.), Division of Neurology (T.-L.P., C.B.) and Endocrinology Division (J.-P.B.), Department of Medicine, Department of Pediatrics (J.-F.L.), and Diagnostic Radiology (K.W.), Department of Medicine, Université de Sherbrooke, Quebec, Canada.
Neurology. 2023 Nov 14;101(20):e1970-e1978. doi: 10.1212/WNL.0000000000207845. Epub 2023 Sep 27.
Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life extends the window of cerebrovascular protection to the postmenopausal period. To investigate this, we examined the relationship between lifetime hormone exposure (LHE) and cerebral small vessel disease in more than 9,000 postmenopausal women in the UK-Biobank.
The cohort consisted of women (aged 40-69 years) who attended one of 22 research centers across the United Kingdom between 2006 and 2010. Women were excluded if they were premenopausal when scanned, had missing reproductive history data, self-reported neurologic disorders, brain cancer, cerebral vascular incidents, head or neurologic injury, and nervous system infection. Endogenous LHE (LHE) was estimated by summing the number of years pregnant (LHE) with the duration of the reproductive period (LHE = age menopause - age menarche). Exogenous LHE (LHE) was estimated by summing the number of years on oral contraceptives and hormone replacement therapy. Cerebral small vessel disease was determined by estimating white matter hyperintensity volume (WMHV) from T2-fluid-attenuated inversion recovery brain MRI (acquired between 2014 and 2021), normalized to intracranial volume and log-transformed. Multiple linear regressions were used to assess the relationship between LHE on WMHV adjusted for age, cardiovascular risk factors, sociodemographics, and LHE.
A total of 9,163 postmenopausal women (age 64.21 ± 6.81 years) were retained for analysis. Average LHE was 39.77 ± 3.59 years. Women with higher LHE showed smaller WMHV (adj- = 0.307, LHE β = -0.007 [-0.012 to -0.002], < 0.01). LHE and LHE were independent contributors to WMHV (adj- = 0.308, << 0.001; LHE β = -0.022 [-0.042 to -0.002], < 0.05; LHE β = -0.006 [-0.011 to -0.001], < 0.05). LHE was not significantly related to WMHV (LHE β = 0.001 [-0.001 to 0.002], > 0.05).
Women with more prolonged exposure to endogenous hormones show relatively smaller burden of cerebral small vessel disease independent of the history of oral contraceptive use or hormone replacement therapy. Our results highlight the critical role endogenous hormones play in female brain health and provide real-world evidence of the protective effects premenopausal endogenous hormone exposure plays on postmenopausal cerebrovascular health.
绝经后脑血管疾病的发病率增加，这通常归因于激素的缺失。目前尚不清楚女性绝经前的激素累积暴露是否会将脑血管保护的窗口期延长至绝经后。为了研究这一点，我们在英国生物银行的 9000 多名绝经后女性中检查了终生激素暴露（LHE）与脑小血管疾病之间的关系。
该队列由年龄在 40-69 岁之间的女性组成，她们于 2006 年至 2010 年期间在英国的 22 个研究中心之一参加了研究。如果女性在扫描时处于绝经前、缺乏生殖史数据、自我报告的神经系统疾病、脑癌、脑血管事件、头部或神经系统损伤以及神经系统感染，则将其排除在外。内源性 LHE（LHE）通过将怀孕的年数（LHE）与生殖期的持续时间相加来估计（LHE=绝经年龄-初潮年龄）。外源性 LHE（LHE）通过将口服避孕药和激素替代疗法的年数相加来估计。脑小血管疾病通过估计 T2 液体衰减反转恢复脑 MRI 中的脑白质高信号体积（WMHV）来确定（在 2014 年至 2021 年之间采集），并将其标准化为颅内体积并进行对数转换。多元线性回归用于评估 LHE 对 WMHV 的影响，调整因素包括年龄、心血管危险因素、社会人口统计学因素和 LHE。
共纳入 9163 名绝经后女性（年龄 64.21±6.81 岁）进行分析。平均 LHE 为 39.77±3.59 年。LHE 较高的女性 WMHV 较小（adj-=0.307，LHEβ=-0.007[-0.012 至-0.002]，<0.01）。LHE 和 LHE 是 WMHV 的独立贡献者（adj-=0.308，<0.001；LHEβ=-0.022[-0.042 至-0.002]，<0.05；LHEβ=-0.006[-0.011 至-0.001]，<0.05）。LHE 与 WMHV 无显著相关性（LHEβ=0.001[-0.001 至 0.002]，>0.05）。
内源性激素暴露时间较长的女性，其脑小血管疾病负担相对较小，这与口服避孕药或激素替代疗法的使用史无关。我们的结果强调了内源性激素在女性大脑健康中的关键作用，并提供了绝经前内源性激素暴露对绝经后脑血管健康具有保护作用的真实世界证据。
