British scientists have suggested that menopause is linked to changes in the brain similar to those seen in Alzheimer’s, and that hormone replacement therapy (HRT) appears not to prevent grey matter loss, reports the BBC.
The researchers speculate that the loss of grey matter in areas involved with memory and emotion might partly explain why women are generally at greater risk of dementia than men.
Their findings, published in the journal Psychological Medicine, come from nearly 125 000 women, of whom 11 000 had MRI brain scans.
Professor Barbara Sahakian, senior author and from Cambridge University, said: “The brain regions where we saw these differences are those that tend to be affected by Alzheimer’s disease. Menopause could make these women vulnerable further down the line, and while not the whole story, it may help explain why we see almost twice as many cases of dementia in women as we do in men.”
The brain changes occurred in:
• an area which has a major role in learning and memory – the hippocampus;
• a region essential for forming memories and spatial navigation – the entorhinal cortex; and
• a part which helps with attention and regulating emotions – the anterior cingulate cortex
White matter and grey matter are both essential parts of the brain and spinal cord. Grey matter consists of neuronal cell bodies and their dendrites (short protrusions that communicate with neurons nearby).
White matter consists of long axons of neurons that transmit impulses to more distant regions of the brain and spinal cord.
Asking for help
HRT can be considered for menopausal symptoms like sleep problems and hot flushes, but there is limited understanding of the effects of menopause and HRT use on the brain, memory and mood, the researchers said.
The study also found that women on HRT were more likely to suffer poor mental health. But many of those already had poorer mental health before being prescribed the medication.
Michelle Dyson from the Alzheimer’s Society said women account for around two-thirds of people living with Alzheimer’s disease in the UK.
“And while we still don’t fully understand why they are more susceptible than men, this large study adds to evidence showing how menopause affects the brain, including physical changes like loss of brain volume.
“But without long-term participant tracking, to check if they later develop dementia, we cannot be sure that these brain changes associated with menopause also increase dementia risk.”
Study details
Emotional and cognitive effects of menopause and hormone replacement therapy
Katharina Zuhlsdorff, Christelle Langley, Richard Bethlehem et al.
Published online by Cambridge University Press on 27 January 2026
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 analysed 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 grey 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 grey 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.
BBC article – Menopause linked to Alzheimer's-like brain changes (Open access)
See more from MedicalBrief archives:
More brain changes for post-menopausal than for pre-menopausal women – Bonn study
HRT should be given earlier as menopause ‘reshapes the brainʼ – Nature Scientific Reports
Early menopause may raise dementia risk later – UK study of 150,000 women