New research indicates that menopausal hormone therapy (MHT) may have a moderate influence on brain health, with effects varying based on a woman’s surgical history, how long the treatment lasted, and her age at the last use of the therapy.
This study, published on October 8 in a Reviewed Preprint in eLife, was characterized by editors as a crucial investigation employing a robust model of brain aging to explore the relationship between MHT and brain health among a substantial cohort of women in the UK. Addressing this issue is deemed critically important since a better understanding of how MHT impacts the brain could lead to more effective and personalized medical support for women experiencing menopause.
Throughout a woman’s life, ovarian hormones like oestrogen and progesterone experience fluctuations, especially during the years leading up to menopause, as ovarian function declines. MHT is typically prescribed to reduce the symptoms associated with these hormonal changes during menopause, with a common belief that it protects brain health and lowers the risk of Alzheimer’s disease, although research on this topic has shown conflicting results.
Claudia Barth, the lead author and researcher at the Division for Mental Health and Substance Abuse at Diakonhjemmet Hospital in Oslo, Norway, states, “The mixed outcomes from earlier studies on MHT and brain health prompt inquiry into how variables such as timing, formulation, and administration method may influence MHT’s effectiveness. In our research, we analyzed the relationships between various MHT variables, distinct MHT regimens, genetic factors, and brain health indicators in middle-aged to older women.”
The study utilized data from the UK Biobank, which includes anonymized genetic, lifestyle, health information, and biological samples. The researchers scrutinized information from nearly 20,000 women who underwent MRI brain scans and were either current or previous MHT users or had never used MHT, with most being postmenopausal. They evaluated the brain MRI images to ascertain the ‘brain age gap’—the disparity between chronological age and brain age—alongside other signs of brain health.
The findings were intriguing. Women who previously used MHT did not show a significant difference in brain age compared to those who had never used it. However, current MHT users exhibited, on average, larger gaps in grey and white matter brain age—suggesting that their brain age was older than their actual age—compared to non-users. They also showed smaller volumes in their left and right hippocampi.
Additionally, the age at which past users last used MHT appeared to impact outcomes, with those older at their last use after menopause having greater brain age gaps and reduced hippocampal volumes. Similar patterns were observed in women who had taken MHT for extended periods.
Interestingly, women using MHT who had undergone surgery to remove their womb and/or both ovaries demonstrated a smaller brain age gap than those without that surgical background. Additionally, there were no notable differences related to MHT variables like dosage, type (synthetic or bioidentical), or method of intake (pill or patch).
The researchers also looked into whether carrying the known Alzheimer’s risk gene, APOE É›4, had any influence on how MHT affected brain health proxies but found no connection.
The authors noted that although there were some slight adverse brain health signs linked to current MHT use and older age at last use, these results do not support a general neuroprotective effect of MHT or significant negative consequences for female brain health.
Barth emphasizes, “Our findings highlight intricate relationships between MHT application and brain health, underscoring the need for personalized MHT strategies. Importantly, our analysis presents population-level correlations and is not meant to inform individual decisions regarding the advantages and disadvantages of MHT.”
The authors also observed that current MHT users were generally younger than those who had previously or never used it, with a lower percentage being postmenopausal (67% compared to 80%). This may indicate that many of these women were experiencing perimenopause, a stage often associated with neurological symptoms like cognitive decline and mood changes. The need for MHT could therefore be a sign of neurological shifts during this transitional phase, potentially stabilizing later on.
In conclusion, Ann Marie de Lange, senior author and Research Fellow in the Department of Clinical Neurosciences at Lausanne University Hospital, Switzerland, stated, “Our findings suggest that the impact of MHT on women’s brain health could vary based on factors such as the timing, duration of use, and prior surgical history. However, since our study is cross-sectional, we cannot definitively establish cause-and-effect relationships. Future research exploring the long-term effects of MHT on brain health is essential for understanding individual risks and benefits. Women globally face critical decisions about MHT, and the current lack of comprehensive research leaves them without sufficient information to make informed choices.”
