New research suggests menopause is associated with brain volume loss in key regions tied to memory and emotions, along with higher rates of anxiety, depression, and sleep issues.
Hormone therapy didn’t prevent these changes, though it may slow age-related declines in reaction speed.
Menopause Linked to Brain Changes and Mental Health Challenges
New research from the University of Cambridge suggests that menopause is associated with measurable changes in the brain, along with higher rates of anxiety, depression, and sleep problems. The findings point to reductions in grey matter volume in several important brain regions during and after menopause.
The study, published today (January 26) in Psychological Medicine, also examined the role of hormone replacement therapy (HRT). While HRT did not appear to prevent these brain or mental health changes, it was linked to a slower decline in reaction speed.
What Happens During Menopause
Menopause marks the stage of life when menstrual periods permanently stop due to declining hormone levels. It most commonly occurs between the ages of 45 and 55 and is often accompanied by symptoms such as hot flashes, low mood, and disrupted sleep. Earlier research has also connected menopause to changes in thinking abilities, including memory, attention, and language skills.
Because of these symptoms, many women are prescribed HRT, especially to help with depression and sleep disturbances. In England, 15% of women received HRT prescriptions in 2023. Despite its widespread use, scientists still know relatively little about how menopause and HRT affect the brain, thinking abilities, and mental health over time.
A Large Study of Nearly 125,000 Women
To explore these questions, Cambridge researchers analyzed data from the UK Biobank involving nearly 125,000 women. Participants were grouped into three categories: those who had not yet reached menopause, those who were post-menopause and had never used HRT, and those who were post-menopause and had used HRT.
Participants completed detailed questionnaires covering menopause symptoms, mental health, sleep habits, and general health. Some also took cognitive tests that measured memory and reaction time. In addition, about 11,000 women underwent magnetic resonance imaging (MRI) scans, allowing researchers to examine differences in brain structure.
The average age at which participants reached menopause was about 49.5 years. Women who used HRT typically began treatment at around age 49.
Mental Health and Sleep After Menopause
Women who had gone through menopause were more likely than those who had not to seek help from a GP or psychiatrist for anxiety, nervousness, or depression. They also tended to score higher on depression questionnaires and were more likely to have been prescribed antidepressants.
At first glance, women who used HRT appeared to have higher levels of anxiety and depression than those who did not. However, deeper analysis showed these mental health differences were already present before menopause began. According to the researchers, this suggests some women may have been prescribed HRT in anticipation that menopause could worsen existing symptoms.
Sleep problems were also more common after menopause. Post-menopausal women were more likely to report insomnia, shorter sleep duration, and ongoing fatigue. Women using HRT reported feeling the most tired overall, even though their total sleep time was similar to that of post-menopausal women who were not taking the medication.
Lifestyle and Mental Health Awareness
Dr Christelle Langley from the Department of Psychiatry said: “Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not. 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.
“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.”
Cognitive Changes and Reaction Time
The researchers also found links between menopause and cognitive performance. Women who were post-menopause and not using HRT showed slower reaction times compared with women who had not yet reached menopause and those who were using HRT. Memory performance, however, did not differ significantly among the three groups.
Dr Katharina Zühlsdorff from the Department of Psychology at the University of Cambridge, said: “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. 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.”
Grey Matter Loss in Key Brain Regions
Brain scans revealed that women who were post-menopause, regardless of HRT use, showed significant reductions in grey matter volume. Grey matter contains nerve cell bodies and plays a central role in processing information, regulating movement, and supporting memory and emotional control.
The most notable changes were seen in the hippocampus (responsible for forming and storing memories), the entorhinal cortex (the ‘gateway’ for passing information between the hippocampus and the rest of the brain), and the anterior cingulate cortex (part of the brain that helps you manage emotions, make decisions, and focus your attention).
Possible Links to Dementia Risk
Professor Barbara Sahakian, the study’s senior author from the Department of Psychiatry, added: “The brain regions where we saw these differences are ones that tend to be affected by Alzheimer’s disease. 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.”
Reference: “Emotional and cognitive effects of menopause and hormone replacement therapy” by Katharina Zuhlsdorff, Christelle Langley, Richard Bethlehem, Varun Warrier, Rafael Romero Garcia and Barbara J Sahakian, 27 January 2026, Psychological Medicine.
DOI: 10.1017/S0033291725102845
The research was funded by the Wellcome Trust, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.
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