Menopause linked to loss of grey matter in the brain, poorer mental health and sleep disturbance

Menopause is linked to reductions in grey matter volume in key brain regions as well as increased levels of anxiety and depression and difficulties with sleep, according to new research from the University of Cambridge.

The study, published today in Psychological Medicine, found that hormone replacement therapy (HRT) does not appear to mitigate these effects, though it can slow the decline in reaction times.

Menopause is a key period in a woman’s life when her periods stop, due to lower hormone levels. It typically affects women between the ages of 45 and 55, during which time they may experience hot flushes, low mood and sleep problems. Menopause has previously been linked to cognitive decline, such as memory, attention and language deficits.

To counter the effects of menopause – particularly depressive symptoms and sleep problems – many women are prescribed HRT. In England, in 2023, 15% of women were prescribed the treatment. However, there is limited understanding of the effects of menopause and subsequent HRT use on the brain, cognition and mental health.

To address this question, researchers at the University of Cambridge analysed data from UK Biobank of almost 125,000 women, who were classified into three categories: pre-menopause, post-menopause who have never used HRT, or post-menopause who have used HRT.

As well as answering questionnaires that included questions related to their experience of menopause, self-reported mental health, sleep patterns and overall health, some participants took part in tests of cognition, including tests of memory and reaction times. Around 11,000 participants also underwent magnetic resonance imaging (MRI) scans, allowing the researchers to look at the structure of their brains.

The average age of onset of menopause among the participants was around 49.5 years, while the average age that women prescribed HRT began their treatment was around 49 years.

Post-menopausal women were more likely than those pre-menopause to have sought help from their GP or a psychiatrist for anxiety, nerves or depression, and to score more highly on questionnaires for symptoms of depression. Similarly, they were more likely to have been prescribed antidepressants.

Although women in the HRT group had greater anxiety and depression compared with the non-HRT group, further analysis showed that these differences in symptoms were already present before menopause. It is possible, say the researchers, that in some cases, a woman’s GP may have prescribed HRT in anticipation of menopause worsening her symptoms.

Women post-menopause were more likely to report insomnia, get less sleep, and feel tired. Those on HRT reported feeling the most tired of all three groups, even though there was no difference in sleep duration between these women and those women post-menopause not on the medication.

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.”

Menopause also appeared to have an impact on cognition. Post-menopausal women who were not on HRT had slower reaction times than those yet to start menopause or who were on HRT. However, there were no significant differences between the three groups when it came to memory tasks.

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.”

In both groups of women post-menopause, the researchers found significant reductions in volume of grey matter – brain tissue that contains nerve cell bodies and helps process information, control movement and manage memory and emotions.

In particular, these differences occurred in the hippocampus (responsible for forming and storing memories); 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).

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.”

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.

Reference

Zühlsdorff, K et al. Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine; 27 Jan 2025; DOI: 10.1017/S0033291725102845