Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort
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 i...
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eLife Sciences Publications Ltd
2025-05-01
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| author | Claudia Barth Liisa AM Galea Emily G Jacobs Bonnie H Lee Lars T Westlye Ann-Marie G de Lange |
| author_facet | Claudia Barth Liisa AM Galea Emily G Jacobs Bonnie H Lee Lars T Westlye Ann-Marie G de Lange |
| author_sort | Claudia Barth |
| collection | DOAJ |
| description | 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 MHT use and female brain health might vary depending on duration of use and past surgical history.
Funding: 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). |
| format | Article |
| id | doaj-art-b45a935c7ebe406eb7ec1492cf1ffc15 |
| institution | OA Journals |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-b45a935c7ebe406eb7ec1492cf1ffc152025-08-20T02:34:42ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.99538Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohortClaudia Barth0https://orcid.org/0000-0001-6544-0945Liisa AM Galea1Emily G Jacobs2https://orcid.org/0000-0003-0001-5096Bonnie H Lee3Lars T Westlye4https://orcid.org/0000-0001-8644-956XAnn-Marie G de Lange5Division for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, NorwayCentre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, CanadaPsychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, United StatesCentre for Addiction and Mental Health, Toronto, CanadaDepartment of Psychology, University of Oslo, Oslo, Norway; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, NorwayDepartment of Psychology, University of Oslo, Oslo, Norway; Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; Department of Psychiatry, University of Oxford, Oxford, United KingdomBackground: 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 MHT use and female brain health might vary depending on duration of use and past surgical history. Funding: 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).https://elifesciences.org/articles/99538neuroimagingwomen's healthmenopausal hormone therapymachine learning |
| spellingShingle | Claudia Barth Liisa AM Galea Emily G Jacobs Bonnie H Lee Lars T Westlye Ann-Marie G de Lange Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort eLife neuroimaging women's health menopausal hormone therapy machine learning |
| title | Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort |
| title_full | Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort |
| title_fullStr | Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort |
| title_full_unstemmed | Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort |
| title_short | Menopausal hormone therapy and the female brain: Leveraging neuroimaging and prescription registry data from the UK Biobank cohort |
| title_sort | menopausal hormone therapy and the female brain leveraging neuroimaging and prescription registry data from the uk biobank cohort |
| topic | neuroimaging women's health menopausal hormone therapy machine learning |
| url | https://elifesciences.org/articles/99538 |
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