Emotional and cognitive effects of menopause and hormone replacement therapy

[Background] Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This stud...

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Detalhes bibliográficos
Autores: Zuhlsdorff, Katharina, Langley, Christelle, Bethlehem, Richard, Warrier, Varun, Romero García, Rafael, Sahakian, Barbara J.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/422413
Acesso em linha:http://hdl.handle.net/10261/422413
https://api.elsevier.com/content/abstract/scopus_id/105028662587
Access Level:acceso abierto
Palavra-chave:Anterior cingulate cortex
Cognition
Entorhinal cortex
Hippocampus
Hormone replacement therapy
Menopause
Mental health
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spelling Emotional and cognitive effects of menopause and hormone replacement therapyZuhlsdorff, KatharinaLangley, ChristelleBethlehem, RichardWarrier, VarunRomero García, RafaelSahakian, Barbara J.Anterior cingulate cortexCognitionEntorhinal cortexHippocampusHormone replacement therapyMenopauseMental health[Background] Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure.[Methods] We analyzed data from nearly 125,000 participants in the UK Biobank to assess associations between menopause, HRT use, and outcomes related to mental health, cognition, and brain morphology. Specifically, we focused on gray matter volumes in the medial temporal lobe (MTL) and anterior cingulate cortex (ACC).[Results] Menopause was associated with increased levels of anxiety, depression, and sleep difficulties. Women using HRT reported greater mental health challenges than post-menopausal women not using HRT. Post-hoc analyses revealed that women prescribed HRT had higher levels of pre-existing mental health symptoms. In terms of brain structure, MTL and ACC volumes were smaller in post-menopausal women compared to pre-menopausal women, with the lowest volumes observed in the HRT group.[Conclusions] Our findings suggest that menopause is linked to adverse mental health outcomes and reductions in gray matter volume in key brain regions. The use of HRT does not appear to mitigate these effects and may be associated with more pronounced mental health challenges, potentially due to underlying baseline differences. These results have important implications for understanding the neurobiological effects of HRT and highlighting the unmet need for addressing mental health problems during menopause.CL and BJS are funded by the Wellcome Trust Collaborative Award 223082/Z/21/Z. The University of Cambridge, Department of Psychiatry research is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and NIHR Applied Research Centre. KZ is funded by the Angharad Dodds John Bursary, Downing College, University of Cambridge and the Foulkes Foundation Fellowship. RRG is funded by the Plan de Generación de Conocimiento (PID2021-122853OA-I00), the Plan de Consolidación (CNS2023–143647) de la Agencia Estatal de Investigación, and the EMERGIA Junta de Andalucía program (EMERGIA20_00139).Peer reviewedCambridge University PressWellcome TrustCambridge Biomedical Research CentreNIHR Applied Research CollaborationsUniversity of CambridgeFoulkes FoundationAgencia Estatal de Investigación (España)Junta de AndalucíaZuhlsdorff, Katharina [0000-0002-8501-4529]Langley, Christelle [0000-0001-5061-2820]Bethlehem, Richard [0000-0002-0714-0685]Warrier, Varun [0000-0003-4532-8571]Romero García, Rafael [0000-0002-5199-4573]Sahakian, Barbara J. [0000-0001-7352-1745]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/422413https://api.elsevier.com/content/abstract/scopus_id/105028662587reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1017/S0033291725102845Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4224132026-05-22T06:33:51Z
dc.title.none.fl_str_mv Emotional and cognitive effects of menopause and hormone replacement therapy
title Emotional and cognitive effects of menopause and hormone replacement therapy
spellingShingle Emotional and cognitive effects of menopause and hormone replacement therapy
Zuhlsdorff, Katharina
Anterior cingulate cortex
Cognition
Entorhinal cortex
Hippocampus
Hormone replacement therapy
Menopause
Mental health
title_short Emotional and cognitive effects of menopause and hormone replacement therapy
title_full Emotional and cognitive effects of menopause and hormone replacement therapy
title_fullStr Emotional and cognitive effects of menopause and hormone replacement therapy
title_full_unstemmed Emotional and cognitive effects of menopause and hormone replacement therapy
title_sort Emotional and cognitive effects of menopause and hormone replacement therapy
dc.creator.none.fl_str_mv Zuhlsdorff, Katharina
Langley, Christelle
Bethlehem, Richard
Warrier, Varun
Romero García, Rafael
Sahakian, Barbara J.
author Zuhlsdorff, Katharina
author_facet Zuhlsdorff, Katharina
Langley, Christelle
Bethlehem, Richard
Warrier, Varun
Romero García, Rafael
Sahakian, Barbara J.
author_role author
author2 Langley, Christelle
Bethlehem, Richard
Warrier, Varun
Romero García, Rafael
Sahakian, Barbara J.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Wellcome Trust
Cambridge Biomedical Research Centre
NIHR Applied Research Collaborations
University of Cambridge
Foulkes Foundation
Agencia Estatal de Investigación (España)
Junta de Andalucía
Zuhlsdorff, Katharina [0000-0002-8501-4529]
Langley, Christelle [0000-0001-5061-2820]
Bethlehem, Richard [0000-0002-0714-0685]
Warrier, Varun [0000-0003-4532-8571]
Romero García, Rafael [0000-0002-5199-4573]
Sahakian, Barbara J. [0000-0001-7352-1745]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Anterior cingulate cortex
Cognition
Entorhinal cortex
Hippocampus
Hormone replacement therapy
Menopause
Mental health
topic Anterior cingulate cortex
Cognition
Entorhinal cortex
Hippocampus
Hormone replacement therapy
Menopause
Mental health
description [Background] Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/422413
https://api.elsevier.com/content/abstract/scopus_id/105028662587
url http://hdl.handle.net/10261/422413
https://api.elsevier.com/content/abstract/scopus_id/105028662587
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.1017/S0033291725102845
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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