Menopausal Hormone Therapy’s Effect on Brain Health

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A recent study suggests that Menopausal Hormone Therapy (MHT) may have moderate effects on brain health, depending on factors like surgical history, treatment duration, and the age at which a woman last used it.

Published in eLife as a Reviewed Preprint, the study is described as an essential look at how MHT relates to brain health, particularly in UK women. This topic is critical because understanding MHT’s effects on the brain can support better, personalized healthcare for women experiencing menopause.

As women approach menopause, ovarian hormones like estrogen and progesterone fluctuate. MHT is often prescribed to ease symptoms from these hormonal changes and is thought to protect brain health and potentially reduce the risk of Alzheimer’s disease. However, evidence on this benefit has been inconsistent.

“Mixed findings from previous studies of MHT and brain health raise the question of whether a combination of timing, formulation and route of administration might play a crucial role in the effectiveness of MHT,” says lead author Claudia Barth, a researcher in the Division for Mental Health and Substance Abuse at Diakonhjemmet Hospital, Oslo, Norway. “In this study, we investigated links between MHT variables, different MHT regimes, genetic factors, and brain measures in middle-to older aged women.”

Using data from the UK Biobank, a resource containing genetic, lifestyle, and health information from a large population, researchers studied nearly 20,000 women who had undergone MRI brain scans. These women included both current and past users of MHT, as well as those who had never used it. The study focused on indicators of brain health, such as the “brain age gap” (the difference between chronological and brain age) and hippocampal volume, an area tied to memory and cognition.

The findings were surprising. For example, women who were currently using MHT showed an older brain age than never-users, as indicated by higher grey and white matter brain age gaps. These current users also showed lower hippocampal volumes. In past users, age at last use made a difference: women who used MHT later in life had a higher brain age gap and smaller hippocampus volumes. Similarly, those who had used MHT for a longer period had similar results.

Interestingly, women on MHT who had undergone surgery to remove their womb or ovaries had a lower brain age gap than MHT users without the surgery. Researchers did not find significant effects related to other MHT factors, such as synthetic versus bioidentical hormones, or the method of administration (pill or patch).

The team also tested for a link between MHT and a known Alzheimer’s risk gene (APOE ɛ4) but found no connection between this gene and MHT’s effect on brain health.

Reflecting on the results, the authors noted that while current MHT use and older age at last use were tied to some modest brain health effects, the findings do not support a strong protective or harmful effect of MHT on the brain.

“The results suggest subtle yet complex relationships between MHT use and brain health, highlighting the necessity for a personalised approach to MHT use,” Barth says. “Importantly, our analyses provide a broad view of population-based associations and are not designed to guide individual-level decisions regarding the benefits versus risks of MHT use.”

Authors also pointed out that current MHT users tended to be younger and included more women in perimenopause than in the past or never-user groups. As perimenopause often brings cognitive and mood changes, the authors suggest that women seeking MHT may be responding to these neurological shifts, which then level off later in life.

“Our results indicate that the effect of MHT on female brain health might vary depending on factors including timing, duration of use and past surgical history,” concludes senior author Ann Marie de Lange, Senior Research Fellow in the Department of Clinical Neurosciences, Lausanne University Hospital, Switzerland. “However, our study is cross-sectional and we cannot establish causality. Future studies mapping the long-term impacts of MHTs on brain health are of immense importance to understand individual risk profiles and benefits. Women worldwide face critical decisions regarding MHT use, yet the current lack of comprehensive research leaves them without the necessary evidence to make informed choices.”

This study highlights the need for ongoing research to give women the best, most personalized advice on MHT as they navigate menopause and consider treatment options for brain health.

Full Credit to: Study highlights complexity of menopausal hormone therapy’s impact on brain health