A large University of Cambridge analysis of UK Biobank data found that post-menopausal women showed smaller grey matter volumes in several brain regions tied to memory and emotional regulation, alongside higher reported anxiety, depression and sleep difficulties. Hormone replacement therapy (HRT) was not associated with preventing these differences, although it was linked with a slower decline in reaction speed.
Researchers at the University of Cambridge analyzed UK Biobank data from nearly 125,000 women to examine associations between menopause, hormone replacement therapy (HRT), mental health, sleep, cognition and brain structure.
Participants were grouped as: women who had not yet reached menopause, post-menopausal women who had never used HRT, and post-menopausal women who had used HRT. The average age at menopause in the dataset was about 49.5 years, and women prescribed HRT typically began treatment at around age 49.
Across questionnaire measures, post-menopausal women were more likely than pre-menopausal women to report seeking help from a GP or psychiatrist for anxiety, nervousness or depression. They also scored higher on depression questionnaires and were more likely to have been prescribed antidepressant medication. Women in the HRT group reported higher levels of anxiety and depression than post-menopausal women who did not use HRT, but additional analyses indicated these differences were already present before menopause began, suggesting HRT may have been prescribed in some cases where symptoms were already emerging.
Sleep problems were also reported more often after menopause, including insomnia, reduced sleep and persistent tiredness. Women using HRT reported the highest levels of fatigue, even though their total sleep duration did not differ from post-menopausal women who were not taking HRT.
On cognitive testing, memory performance did not differ significantly across the three groups. Reaction time, however, was slower in post-menopausal women who were not using HRT compared with women who had not yet reached menopause and post-menopausal women who were using HRT.
In a subset of roughly 11,000 women who underwent MRI brain scanning, researchers found smaller grey matter volumes in post-menopausal women in regions including the hippocampus, entorhinal cortex and anterior cingulate cortex. These differences were observed regardless of whether women had used HRT.
Dr. Christelle Langley, from the University of Cambridge Department of Psychiatry, said menopause can be “life-changing” and argued that lifestyle measures such as staying active and eating a healthy diet are particularly important during this period. Dr. Katharina Zühlsdorff, from the university’s Department of Psychology, said reaction times typically slow with age, adding that menopause appeared to accelerate this slowing, while HRT “appears to put the brakes on” slightly.
Professor Barbara Sahakian, the senior author, said the brain regions showing differences are among those affected in Alzheimer’s disease, and suggested the findings may offer one possible clue toward why dementia is more common in women than in men, while emphasizing this would not be the only factor.
The study was published in the journal Psychological Medicine.
