Objective To assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy. Design Two nested case-control studies. Setting UK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data. Participants 118 501 women aged 55 and older with a primary diagnosis of dementia between 1998 and 2020, matched by age, general practice, and index date to 497 416 female controls. Main outcome measures Dementia diagnoses from general practice, mortality, and hospital records; odds ratios for menopausal hormone treatments adjusted for demographics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Results Overall, 16 291 (14%) women with a diagnosis of dementia and 68 726 (14%) controls had used menopausal hormone therapy more than three years before the index date. Overall, no increased risks of developing dementia associated with menopausal hormone therapy were observed. A decreased global risk of dementia was found among cases and controls younger than 80 years who had been taking oestrogen-only therapy for 10 years or more (adjusted odds ratio 0.85, 95% confidence interval 0.76 to 0.94). Increased risks of developing specifically Alzheimer’s disease were found among women who had used oestrogen-progestogen therapy for between five and nine years (1.11, 1.04 to 1.20) and for 10 years or more (1.19, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10 000 woman years. Detailed risk associations for the specific progestogens studied are also provided. Conclusion This study gives estimates for risks of developing dementia and Alzheimer’s disease in women exposed to different types of menopausal hormone therapy for different durations and has shown no increased risks of developing dementia overall. It has shown a slightly increased risk of developing Alzheimer’s disease among long term users of oestrogen-progestogen therapies. To guarantee the confidentiality of personal and health information, only the authors have had access to the data during the study in accordance with the relevant licence agreements. Access to the QResearch data is according to the information on the QResearch website ([www.qresearch.org][1]). CPRD linked data were provided under a licence that does not permit sharing. [1]: http://www.qresearch.org

中文翻译：

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更年期激素治疗的使用和痴呆风险：使用 QResearch 和 CPRD 数据库的嵌套病例对照研究

目的评估与绝经激素治疗的不同类型和持续时间相关的痴呆风险。设计两个嵌套病例对照研究。使用与医院、死亡率和社会剥夺数据的所有链接，为 QResearch 或临床实践研究数据链接 (CPRD) 设置英国的一般做法。参与者 118,501 名 55 岁及以上的女性，在 1998 年至 2020 年期间被初步诊断为痴呆症，按年龄、一般做法和索引日期与 497,416 名女性对照组相匹配。主要结果测量来自全科实践、死亡率和医院记录的痴呆症诊断；更年期激素治疗的优势比针对人口统计学、吸烟状况、饮酒、合并症、家族史和其他处方药进行了调整。结果 总体而言，16 291 (14%) 名被诊断为痴呆症的女性和 68 726 (14%) 名对照者在指数日期前三年以上使用过更年期激素治疗。总体而言，未观察到与更年期激素治疗相关的痴呆风险增加。在年龄小于 80 岁且仅接受雌激素治疗 10 年或更长时间的病例和对照组中发现痴呆的整体风险降低（调整后的优势比为 0.85，95% 置信区间为 0.76 至 0.94）。在使用雌激素 - 孕激素治疗 5 至 9 年（1.11、1.04 至 1.20）和 10 年或更长时间（1.19、1.06 至 1.33）的女性中发现患阿尔茨海默病的风险增加。这分别相当于每 10 000 名妇女年增加 5 例和 7 例病例。还提供了所研究的特定孕激素的详细风险关联。结论 本研究评估了接受不同类型更年期激素治疗不同持续时间的女性患痴呆症和阿尔茨海默病的风险，并表明总体上没有增加患痴呆症的风险。它表明长期使用雌激素 - 孕激素疗法的人患阿尔茨海默病的风险略有增加。为保证个人和健康信息的机密性，根据相关许可协议，只有作者可以访问研究期间的数据。根据 QResearch 网站 ([www.qresearch.org][1]) 上的信息访问 QResearch 数据。CPRD 链接数据是根据不允许共享的许可证提供的。[1]：http://www.