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October 23, 2024 — A recent study published in eLife on October 8 underscores the nuanced relationship between menopausal hormone therapy (MHT) and brain health, suggesting that the effects of MHT may be influenced by a woman’s age at last use, duration of treatment, and surgical history. This comprehensive investigation sheds light on an area of considerable significance as many women navigate the challenges of menopause and seek effective medical support.
The research, led by Claudia Barth from Diakonhjemmet Hospital in Oslo, utilized data from the UK Biobank, which includes extensive health information and biological samples from a large population. The study analyzed nearly 20,000 women, assessing brain health through MRI scans and examining the so-called ‘brain age gap’—the difference between chronological age and brain age.
Historically, MHT has been prescribed to alleviate menopausal symptoms, with some studies suggesting a potential protective effect against cognitive decline and Alzheimer’s disease. However, evidence has been inconsistent, prompting the need for further exploration.
“Our findings raise important questions about how variables such as timing, formulation, and administration route might influence the effectiveness of MHT,” Barth noted. The research team discovered that women currently using MHT exhibited a higher brain age gap, indicating their brains appeared older than their actual age, compared to those who had never used MHT. Additionally, these women demonstrated reduced volumes in critical brain regions, such as the hippocampus.
Interestingly, among past MHT users, the timing of last use was pivotal. Women who ceased MHT at an older age exhibited larger brain age gaps and smaller hippocampal volumes. Conversely, those who underwent surgeries to remove their uterus and/or ovaries showed a lower brain age gap than their counterparts who had not experienced such procedures.
Despite assessing the impact of genetic factors, including the APOE ɛ4 gene associated with Alzheimer’s risk, researchers found no significant correlation with MHT-related variables, including dosage or formulation type.
While the study suggests that current MHT usage might be linked to modest adverse brain health outcomes, it does not provide evidence for a broad neuroprotective effect. The authors advocate for a personalized approach to MHT, emphasizing that their analyses represent population-level trends rather than specific medical guidance.
“Understanding the interplay of timing, duration, and individual medical history is crucial for women considering MHT,” said Ann Marie de Lange, senior author and Senior Research Fellow at Lausanne University Hospital. “This study highlights the importance of ongoing research to clarify the long-term impacts of MHT on brain health, helping women make informed decisions regarding their treatment options.”
With a significant proportion of current MHT users being younger and fewer identified as postmenopausal, the need for therapy may signal neurological changes during perimenopause, a phase often accompanied by cognitive and mood fluctuations.
The researchers call for further longitudinal studies to comprehensively evaluate the risks and benefits of MHT, ensuring women worldwide receive the evidence-based guidance necessary for their health decisions during the menopause transition.
