The Complex Impact of Menopausal Hormone Therapy on Brain Health

New research underscores the nuanced effects of menopausal hormone therapy (MHT) on brain health, revealing how individual factors such as age, duration of therapy, and surgical history influence outcomes. Published in eLife, this study delves into the intricate relationships between MHT and brain health metrics among nearly 20,000 women, using data from the extensive UK Biobank.

In an analysis of brain MRI scans, researchers found that current MHT users exhibited higher "brain age gaps" — differences between chronological and brain age — and smaller hippocampal volumes, both indicators of potential adverse effects on brain health. However, these findings were complex: past MHT users did not show such discrepancies, suggesting that ongoing MHT use may interact differently with brain aging compared to discontinuation. Additionally, women who had taken MHT longer or continued it until an older age showed more pronounced brain age gaps and reduced hippocampal sizes.

These findings carry implications for the personalization of MHT. While MHT has been touted for its potential to protect brain health and mitigate Alzheimer’s disease risk, this study highlights that not all women may benefit equally. For instance, surgical history also influenced outcomes: women with hysterectomies or oophorectomies while on MHT had lower brain age gaps compared to those without surgical histories, underscoring the individualized nature of therapy effects.

The study adds to ongoing discussions regarding MHT’s risks and benefits, especially since past users did not exhibit adverse brain characteristics, which might imply a time-dependent effect. Yet, the study authors stress that MHT’s long-term impact remains inadequately understood. The cross-sectional design of the study limits causal conclusions, but the findings emphasize the need for personalized approaches to MHT and suggest that women with specific histories might experience different neurological outcomes.