Menopause associated with adverse mental health, reduced grey matter volume

A large population-based study has linked menopause to reductions in grey matter in key brain regions, alongside higher rates of anxiety, depression, sleep disturbance and subtle cognitive changes, with hormone replacement therapy (HRT) not appearing to offset most of these effects, according to research published in Psychological Medicine.¹

Examining menopause and the brain

Researchers from the University of Cambridge analyzed data from nearly 125,000 women enrolled in the UK Biobank to explore how menopause and HRT use relate to mental health, cognition, and brain structure. Participants were categorized as pre-menopausal, post-menopausal with no history of HRT use, or post-menopausal with HRT use.

In addition to questionnaires on mental health, sleep and overall health, subsets of participants completed cognitive testing, including reaction time and memory tasks. Approximately 11,000 women also underwent magnetic resonance imaging (MRI) to assess brain structure.²

The average age of menopause onset among participants was approximately 49.5 years, while the average age of starting HRT was around 49 years.

Are mental health and sleep challenges more common after menopause?

According to the research, and across the cohort, post-menopausal women were more likely than pre-menopausal women to report mental health difficulties. Specifically, they were more likely to have sought help from a general practitioner or psychiatrist for anxiety, nerves, or depression and to score higher on questionnaires measuring depressive symptoms. They were also more likely to have been prescribed antidepressants.

Women who used HRT reported higher levels of anxiety and depression than post-menopausal women who had never used HRT. However, further analyses suggested these mental health differences were already present before menopause, indicating that HRT users may have had greater baseline symptom burden rather than worsening caused by the therapy itself.^1,2

Sleep problems were also more common after menopause. Post-menopausal women were more likely to report insomnia, shorter sleep duration and increased fatigue. Women using HRT reported feeling the most tired of all 3 groups, despite sleeping a similar amount to post-menopausal women not using HRT.²

MRI analyses showed that post-menopausal women had lower grey matter volumes compared with pre-menopausal women, with the smallest volumes observed among women who had used HRT. These reductions were concentrated in brain regions critical for memory and emotional regulation, including^1,2:

• The hippocampus
• The entorhinal cortex
• The anterior cingulate cortex

“The brain regions where we saw these differences are ones that tend to be affected by Alzheimer’s disease,” said Barbara Sahakian, of the Department of Psychiatry at Cambridge University, and the study’s senior author. “Menopause could make these women vulnerable further down the line. While not the whole story, it may help explain why we see almost twice as many cases of dementia in women than in men.”²

Reaction time slows, but HRT may modestly help

According to cognitive testing, post-menopausal women not using HRT had slower reaction times compared with pre-menopausal women and those using HRT. Memory performance, however, did not differ significantly across groups.^1,2

“As we age, our reaction times tend to get slower – it’s just a part of the natural ageing process and it happens to both women and men,” added Katharina Zühlsdorff, PhD, Department of Psychology, University of Cambridge. “You can imagine being asked a question at a quiz – while you might still arrive at the correct answer as your younger self, younger people would no doubt get there much faster. Menopause seems to accelerate this process, but HRT appears to put the brakes on, slowing the ageing process slightly.”²

“Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not,” said Christelle Langley, of the university’s Department of Psychiatry.

“A healthy lifestyle – exercising, keeping active and eating a healthy diet, for example – is particularly important during this period to help mitigate some of its effects,” said Langley. “We all need to be more sensitive to not only the physical, but also the mental health of women during menopause, however, and recognise when they are struggling. There should be no embarrassment in letting others know what you’re going through and asking for help.”

References:

1. Zühlsdorff, K et al. Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine. January 27, 2026. DOI: 10.1017/S0033291725102845
2. Menopause linked to loss of grey matter in the brain, poorer mental health and sleep disturbance. Cambridge University. January 26, 2026. Accessed January 27, 2026. https://www.eurekalert.org/news-releases/1113527?