Division of Psychiatry (HKP, NM), University College London, London, UK.
Department of Primary Care and Population Health (LM), University College London, London, UK.
Am J Geriatr Psychiatry. 2024 Jul;32(7):792-805. doi: 10.1016/j.jagp.2024.01.025. Epub 2024 Jan 23.
The protective role of estrogen in the development of dementia remains uncertain. We investigated the role of lifetime cumulative exposure to estrogen in dementia in the UK Biobank.
Reproductive characteristics, including estrogen length and history of surgery (hysterectomy/oophorectomy), were used as exposure variables. Cox Proportional Hazard models were used to estimate hazard ratios (HR) for the development of dementia.
A total of 273,260 female participants were included in this study. Compared to women with the shortest estrogen length, women with the longer estrogen length (38-42) had a 28% decreased risk of dementia (HR = 0.718, 95% confidence interval [CI] = 0.651-0.793). Women with later last age at estrogen exposure (50-52) had a 24% decreased risk for dementia (HR = 0.763, 95% CI = 0.695-0.839) compared to women with younger age at last estrogen exposure (≤45). Later age at menarche (≥15) was associated with a 12% increased risk for dementia (HR = 1.121, 95% CI = 1.018-1.234) compared to women with earlier age at menarche (≤12). Women with a history of surgery had an 8% increased risk of dementia (HR = 1.079, 95% CI = 1.002-1.164) compared to women without a history of surgery.
This study found that more prolonged exposure to estrogen (longer estrogen length and later age at last estrogen exposure) had a decreased risk for dementia, and shorter exposure to estrogen (later age at menarche and history of reproductive surgery) had an increased risk for dementia. Based on the results of this study, estrogen might have a protective role in women in the development of dementia.
雌激素在痴呆发展中的保护作用仍不确定。我们在英国生物库中研究了女性一生中累积暴露于雌激素与痴呆的关系。
生殖特征,包括雌激素长度和手术史(子宫切除术/卵巢切除术),被用作暴露变量。使用 Cox 比例风险模型估计痴呆发展的风险比(HR)。
共纳入 273260 名女性参与者。与雌激素长度最短的女性相比,雌激素长度较长(38-42 年)的女性痴呆风险降低 28%(HR=0.718,95%置信区间 [CI] = 0.651-0.793)。与雌激素末次暴露年龄较小(≤45 岁)的女性相比,末次暴露年龄较晚(50-52 岁)的女性痴呆风险降低 24%(HR=0.763,95%CI=0.695-0.839)。初潮年龄较晚(≥15 岁)与痴呆风险增加 12%相关(HR=1.121,95%CI=1.018-1.234),与初潮年龄较早(≤12 岁)的女性相比。有手术史的女性痴呆风险增加 8%(HR=1.079,95%CI=1.002-1.164),而无手术史的女性痴呆风险无显著增加。
本研究发现,更长时间暴露于雌激素(更长的雌激素长度和末次雌激素暴露较晚)可降低痴呆风险,而较短时间暴露于雌激素(初潮年龄较晚和生殖手术史)可增加痴呆风险。基于这项研究的结果,雌激素可能在女性痴呆的发展中具有保护作用。