Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort

作者：Cláudia Barth, Liisa A.M. Galea, Emily G. Jacobs, Bonnie H. Lee, Lars T. Westlye, Ann‐Marie G. de Lange · 发表于：eLife · 年份：2025 · DOI：10.7554/elife.99538.3 · 被引用次数：11 · 研究领域：Menopause: Health Impacts and Treatments、Estrogen and related hormone effects、Cancer-related cognitive impairment studies

Background: 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. Methods: 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. Results: 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 younger gray matter brain age relative to MHT users without such history. We found no associations by APOE ε4 status and with other MHT variables. Conclusions: Our results indicate that population-level associations between...