Barth Claudia, Galea Liisa A M, Jacobs Emily G, Lee Bonnie H, Westlye Lars T, de Lange Ann-Marie G
Division for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.
Centre for Addiction and Mental Health, Toronto, Canada.
Elife. 2025 May 29;13:RP99538. doi: 10.7554/eLife.99538.
Menopausal hormone therapy (MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in females from the UK Biobank.
19,846 females with magnetic resonance imaging data were included. Detailed MHT prescription data from primary care records was available for 538. We tested for associations between the brain measures (i.e. gray/white matter brain age, hippocampal volumes, white matter hyperintensity volumes) and MHT user status, age at first and last use, duration of use, formulation, route of administration, dosage, type, and active ingredient. We further tested for the effects of a history of hysterectomy ± bilateral oophorectomy among MHT users and examined associations by APOE ε4 status.
Current MHT users, not past users, showed older gray and white matter brain age, with a difference of up to 9 mo, and smaller hippocampal volumes compared to never-users. Longer duration of use and older age at last use post-menopause was associated with older gray and white matter brain age, larger white matter hyperintensity volume, and smaller hippocampal volumes. MHT users with a history of hysterectomy ± bilateral oophorectomy showed gray matter brain age relative to MHT users without such history. We found no associations by APOE ε4 status and with other MHT variables.
Our results indicate that population-level associations between MHT use and female brain health might vary depending on duration of use and past surgical history.
The authors received funding from the Research Council of Norway (LTW: 223273, 249795, 273345, 298646, 300768), the South-Eastern Norway Regional Health Authority (CB: 2023037, 2022103; LTW: 2018076, 2019101), the European Research Council under the European Union's Horizon 2020 research and innovation program (LTW: 802998), the Swiss National Science Foundation (AMGdL: PZ00P3_193658), the Canadian Institutes for Health Research (LAMG: PJT-173554), the Treliving Family Chair in Women's Mental Health at the Centre for Addiction and Mental Health (LAMG), womenmind at the Centre for Addiction and Mental Health (LAMG, BHL), the Ann S. Bowers Women's Brain Health Initiative (EGJ), and the National Institutes of Health (EGJ: AG063843).
更年期激素疗法（MHT）通常被认为具有神经保护作用，但结果并不一致。在此，我们对英国生物银行中女性的MHT使用情况和大脑特征进行了全面研究。
纳入了19846名有磁共振成像数据的女性。其中538名女性可获取来自初级保健记录的详细MHT处方数据。我们测试了大脑测量指标（即灰质/白质脑龄、海马体体积、白质高信号体积）与MHT使用者状态、首次和末次使用年龄、使用时长、剂型、给药途径、剂量、类型和活性成分之间的关联。我们还进一步测试了MHT使用者中子宫切除术±双侧卵巢切除术史的影响，并按APOE ε4状态检查了关联。
与从未使用者相比，当前MHT使用者而非过去使用者的灰质和白质脑龄更大，相差可达9个月，且海马体体积更小。使用时长较长以及绝经后末次使用年龄较大与灰质和白质脑龄较大、白质高信号体积较大以及海马体体积较小相关。有子宫切除术±双侧卵巢切除术史的MHT使用者相对于无此类病史的MHT使用者显示出灰质脑龄。我们未发现APOE ε4状态以及与其他MHT变量之间的关联。
我们的结果表明，MHT使用与女性大脑健康之间的人群水平关联可能因使用时长和既往手术史而异。
作者获得了挪威研究理事会（LTW：223273、249795、273345、298646、300768）、挪威东南部地区卫生局（CB：2023037、2022103；LTW：2018076、2019101）、欧盟“地平线2020”研究与创新计划下的欧洲研究理事会（LTW：802998）、瑞士国家科学基金会（AMGdL：PZ00P3_193658）、加拿大卫生研究院（LAMG：PJT - 173554）、成瘾与心理健康中心的特里林妇女心理健康家庭主席职位（LAMG）、成瘾与心理健康中心的womenmind（LAMG、BHL）、安·S·鲍尔斯妇女大脑健康倡议（EGJ）以及美国国立卫生研究院（EGJ：AG063843）的资助。
