Emotional and cognitive effects of menopause and hormone replacement therapy

Abstract

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.