Fresh research analyzing data from nearly 125,000 women in the UK Biobank has revealed significant associations between menopause, hormone replacement therapy (HRT) and changes in brain structure, mental health, and cognitive function. The study, published in the journal The Conversation, adds to a growing body of evidence highlighting the far-reaching effects of the menopausal transition.
Researchers categorized participants into three groups: pre-menopausal, post-menopausal, and post-menopausal women using HRT. The average age of menopause was approximately 49 years old, with HRT typically initiated around the same age. The analysis showed that menopause was linked to poorer sleep quality, increased mental health challenges, and discernible alterations within the brain itself.
Post-menopausal women reported a higher incidence of anxiety and depression compared to their pre-menopausal counterparts. They were also more likely to seek professional help from GPs or psychiatrists and to be prescribed antidepressant medication. Sleep disturbances, including insomnia, shorter sleep duration, and increased fatigue, were also more prevalent after menopause.
Brain imaging revealed reductions in grey matter volume following menopause, particularly in regions crucial for learning, memory – the hippocampus and entorhinal cortex – and emotional regulation and attention, specifically the anterior cingulate cortex. These areas are also among the first affected in Alzheimer’s disease, raising concerns about a potential link between menopause-related brain changes and an increased risk of dementia in later life, a concern echoed by the National Health Service (NHS).
Although, the study found that HRT did not appear to mitigate the reduction in brain grey matter. Women using HRT reported higher levels of anxiety and depression compared to post-menopausal women who had never used HRT. Further analysis suggested that pre-existing mental health conditions may have been a factor in the decision to begin HRT, rather than being caused by the treatment itself.
Despite the findings regarding mental health, HRT did demonstrate a potential benefit in cognitive performance, specifically in psychomotor speed. Post-menopausal women who had never used HRT exhibited slower reaction times compared to both pre-menopausal women and post-menopausal women who had used HRT, indicating a potential slowing of menopause-related declines in psychomotor speed.
The research highlights the complexity of HRT and the need for further investigation. While HRT is a safe and effective treatment for most experiencing menopause and perimenopause, according to the NHS, studies on its long-term effects, particularly regarding dementia risk, have yielded conflicting results. Some studies suggest an increased risk, while others indicate a decreased risk.
A separate study of 538 women conducted through the UK Biobank, referenced in the research, found that the effects of HRT did not appear to differ based on formulation, route of administration, or duration of use. However, the study also revealed that a significant proportion – 25% – of women using the highest licensed dose of HRT still had low estradiol levels (around 200 picomoles per liter), suggesting that many may not be receiving an optimal dose for symptom relief. Optimal plasma levels are considered to be between 220-550 picomoles per liter.
Researchers emphasize the importance of resolving the question of HRT’s overall benefits, including its potential to prevent brain grey matter volume reductions and reduce dementia risk, and determining the optimal dosage and route of administration. They also suggest that adopting healthy lifestyle habits – including regular exercise, cognitively stimulating activities, a nutritious diet, sufficient sleep, and strong social connections – may help mitigate menopause-related changes in brain health and cognitive function. Regular physical activity, for example, has been shown to increase the size of the hippocampus, potentially counteracting some of the reductions observed during menopause.
