Study highlights the complexity of the impact of menopausal hormone therapy on brain health

Study highlights the complexity of the impact of menopausal hormone therapy on brain health

Associations between brain MRI measurements and MHT user status. Credit: (2024). DOI: 10.7554/eLife.99538.1

Research suggests that menopausal hormone therapy (MHT) may have moderate effects on brain health, but this depends on past surgical history, duration of treatment, and the woman’s age at last use.

The research was published as a review on October 8 preprint in eLifewas described by editors as an important study, using a robust model of brain aging, into the associations between MHT and brain health in a large population of British women. The work addresses a topic that the editors believe is of great importance because MHT and its effect on the brain need to be better understood in order to provide effective and individualized medical support to women going through menopause.

Ovarian hormones such as estrogen and progesterone fluctuate throughout a woman’s lifespan, and especially during the years leading up to menopause, when ovarian function begins to decline. MHT is often prescribed to minimize the symptoms of these fluctuations during menopause and is widely believed to protect the brain and reduce the risk of Alzheimer’s disease, but the evidence supporting this is conflicting.

“Mixed findings from previous studies of MHT and brain health raise the question of whether a combination of timing, formulation and route of administration could play a critical role in the effectiveness of MHT,” said lead author Claudia Barth, a researcher in the Department of MHT. Mental health and substance abuse in Diakonhjemmet Hospital, Oslo, Norway. “In this study, we examined associations between MHT variables, different MHT regimens, genetic factors, and brain measurements in middle-aged to older women.”

The researchers used data from the UK Biobank, which contains anonymized genetic, lifestyle and health information and biological samples. They analyzed data from nearly 20,000 women who had undergone MRI brain scans and were currently or previously using MHT or had never used MHT at all, most of whom reported that they had passed menopause. They studied MRI images of the brain to determine the “brain age gap” (the difference between chronological and brain age) and other indicators of brain health.

The team says the results were confusing. Women who had used MHT in the past showed no significant difference in brain age compared to never users. But women who were current MHT users had, on average, larger differences in gray and white matter brain age (suggesting that their brain age was older than their actual chronological age) than women who had never used MHT. They also had smaller brain volumes to the left and right of the hippocampus.

Additionally, among former users, the women’s age when they last used MHT made a difference. Those who were older at the time of their last postmenopausal use had a larger brain age difference and lower hippocampal volumes. Similar results were found in women who used MHT for longer.

Women taking MHT who had surgery to remove their uterus and/or both ovaries had a smaller brain age difference than women receiving MHT without the same surgical history. And unexpectedly, there was no difference in MHT-related variables such as dose or active ingredients, whether it was synthetic or bioidentical, or taken as a pill or patch.

The researchers also assessed whether a known risk gene for Alzheimer’s disease, called APOE ɛ4, influenced the effect of MHT on brain health and again found no link.

In considering the results, the authors noted that although there were some modest adverse brain health markers associated with current MHT use and that women were at an older age at last use, the findings do not support an overall neuroprotective effect of MHT , nor serious adverse effects on the female population. brain.

“The results suggest subtle but complex relationships between MHT use and brain health, highlighting the need for a personalized approach to MHT use,” says Barth. “Importantly, our analyzes provide a broad view of population-based associations and are not intended to guide individual-level decisions about the benefits versus risks of MHT use.”

The authors add that current MHT users were significantly younger than former users and never users, and that approximately a smaller proportion were postmenopausal (67% versus 80%), suggesting that a greater proportion of these women may be in perimenopause, which is often accompanied by neurological symptoms such as cognitive decline and mood swings. The need for MHT could therefore be an indicator of neurological changes during this transition, which stabilize later in life, they suggest.

“Our results indicate that the effect of MHT on female brain health may vary depending on factors such as timing, duration of use and past surgical history,” concludes senior author Ann Marie de Lange, Senior Research Fellow at the Department of Clinical Neurosciences, University of Lausanne. Hospital, Switzerland.

“However, our study is cross-sectional and we cannot establish causality. Future studies identifying the long-term effects of MHTs on brain health are extremely important to understand individual risk profiles and benefits. Women around the world are faced with crucial decisions regarding MHT use, but the current lack of comprehensive research leaves them without the necessary evidence to make informed choices.”

More information:
Claudia Barth et al, Menopausal hormone therapy and the female brain: using neuroimaging and prescription record data from the UK Biobank cohort, eLife (2024). DOI: 10.7554/eLife.99538.1

Magazine information:
eLife


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