Menopause May Affect Brain Structure, Mental Health And Sleep, Research Shows

Menopause may be associated with structural changes in the brain, along with worsening mental health and sleep-related problems, according to a large new study conducted by researchers at the University of Cambridge. The findings suggest that the transition, which marks the end of a woman’s reproductive years, could have deeper neurological and psychological implications than previously understood.

The study, published in the journal Psychological Medicine, reports that women who have gone through menopause show reduced volumes of grey matter in several critical brain regions. These changes were accompanied by higher rates of anxiety and depression, increased sleep disturbances, and greater fatigue. The researchers also found that while hormone replacement therapy (HRT) did not appear to reverse these brain changes or improve mental health outcomes, it was linked to slightly better reaction times.

Menopause occurs when menstrual cycles permanently stop due to declining levels of reproductive hormones, most notably oestrogen. This transition typically takes place between the ages of 45 and 55 and is often accompanied by symptoms such as hot flushes, mood changes, and sleep difficulties. Previous studies have linked menopause to cognitive changes, including problems with memory, attention, and language skills.

HRT is commonly prescribed to help manage menopausal symptoms, particularly mood disturbances and sleep problems. In England alone, around 15% of women were prescribed HRT in 2023. Despite its widespread use, scientists still have a limited understanding of how menopause—and the use of hormone therapy afterward—affects brain structure, mental well-being, and cognitive performance.

To explore these questions, the Cambridge team analysed data from nearly 125,000 women enrolled in the UK Biobank. Participants were divided into three groups: women who had not yet reached menopause, post-menopausal women who had never used HRT, and post-menopausal women who had used HRT.

The women completed detailed questionnaires covering menopausal symptoms, mental health history, sleep patterns, and general health. Many also took part in cognitive tests assessing memory and reaction speed. Additionally, around 11,000 participants underwent magnetic resonance imaging (MRI), enabling researchers to examine differences in brain structure.

The average age at which participants experienced menopause was approximately 49.5 years, while women who used HRT typically began treatment around the age of 49.

The analysis revealed that women who had gone through menopause were significantly more likely than pre-menopausal women to seek medical help for anxiety or depression. They were also more likely to score higher on depression-related questionnaires and to have been prescribed antidepressant medication.

Interestingly, women who had used HRT showed higher levels of anxiety and depression than post-menopausal women who had never taken the therapy. However, further analysis indicated that these mental health differences were already present before menopause, suggesting that HRT may have been prescribed in anticipation of worsening symptoms rather than causing them.

Sleep-related issues were also more common among post-menopausal women. They were more likely to report insomnia, shorter sleep duration, and persistent tiredness. Women using HRT reported feeling the most fatigued overall, despite sleeping for similar durations as those not on hormone therapy.

Dr. Christelle Langley, from the University of Cambridge’s Department of Psychiatry, emphasised that menopause is a major life transition for most women, regardless of whether they take HRT. She stressed the importance of maintaining a healthy lifestyle during this period, including regular physical activity and balanced nutrition, to help reduce some of the associated challenges. She also highlighted the need for greater awareness and sensitivity toward women’s mental health during menopause, encouraging open conversations and help-seeking without stigma.

The researchers also observed changes in cognitive performance. Women who were post-menopausal and not using HRT showed slower reaction times compared with pre-menopausal women and those on hormone therapy. However, no meaningful differences were found between the groups in memory-related tasks.

Dr. Katharina Zühlsdorff, from the Department of Psychology, explained that reaction time naturally slows with age in both men and women. Menopause appears to accelerate this process, she said, while HRT may modestly slow it down.

MRI scans revealed that post-menopausal women—regardless of HRT use—had lower grey matter volume in brain regions critical for memory, emotional regulation, and attention. These included the hippocampus, entorhinal cortex, and anterior cingulate cortex.

Professor Barbara Sahakian, the study’s senior author, noted that these regions are also commonly affected in Alzheimer’s disease. She suggested that menopause-related brain changes may contribute to women’s higher long-term risk of dementia, potentially helping to explain why women account for nearly twice as many dementia cases as men.