A new study published in eLife shows subtle effects of menopausal hormone therapy on the brain, indicating that women in menopause require individualized approaches to treatment. The analysis is based on data from almost 20,000 UK Biobank women. It points to the fact that the age and duration of therapy, as well as surgical history, remarkably depend on the impact of MHT on women’s brain health.
Women in the menopausal transition have alterations in ovarian hormones, mainly estrogen and progesterone. Hormone therapy, commonly MHT, is prescribed for the relief of menopausal symptoms and is often thought to be protective against cognitive decline as well as diseases like Alzheimer’s. However, findings regarding its efficacy have been conflicting and there is a more fundamental need for information on its effects.
Lead author Claudia Barth, from Diakonhjemmet Hospital in Oslo, explained that previous studies showed inconsistent results regarding the effects of MHT on brain health. “The timing, formulation, and method of administration may be crucial to the effectiveness of MHT,” she said. To carry out these investigations, the authors examined associations between brain MRI scans and other health outcomes of women with different histories of MHT use.
The findings were that brain age gaps of the current users were higher, thereby implying that the brains of these women looked older than their chronological age compared to that of nonusers of MHT. Another finding is that current users had smaller hippocampal volumes. The hippocampus is a vital part of the brain in charge of memory and learning. On the other hand, past use of MHT did not differ from nonusers about brain age and hippocampal size.
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Interestingly, the timing of MHT use was also important. Women who discontinued MHT later in life or who used the drugs for a longer duration had larger brain age disparities and smaller hippocampal volumes. Inversely, women who had a history of surgeries such as hysterectomies or oophorectomies while on MHT had lower brain age disparities.
The study also looked into whether there were underlying genetic factors, like the APOE É›4 gene, associated with a heightened risk of Alzheimer’s disease that would influence the MHT–brain health association. However, no associations were established in this regard, suggesting that genetic predispositions may not be the mediators between the MHT effects on brain health.
The authors temper broad inferences of neuroprotective benefits with MHT. “While modest adverse brain health characteristics were associated with current MHT use, our findings do not support a universal neuroprotective effect,” Barth noted. The results point to the need for personalized approaches to MHT regimens tailored to particular health profiles and histories.
Current users were younger and less likely to be postmenopausal than past and never-users, implying that the desire for MHT may be related to neurological changes during the perimenopausal transition. These transitions might stabilize over time, which hints at a possible biological underpinning of MHT usage.
However, the study was cross-sectional-that is, the causality cannot be determined. “Future longitudinal studies need to be performed to determine what MHT will do to the brain in the long term,” claims senior author Ann Marie de Lange from Lausanne University Hospital. “Women worldwide are having to make life-altering decisions about MHT use, and currently there’s a chasm of comprehensive research with which to guide this decision.”.
This study sheds some light on the complex relationships between MHT, brain health, and individual differences among women. Further research in this area will continue the development of informed, differentiated strategies for MHT that better respond to women’s needs and concerns under menopause.
MHT (also known as Hormone Replacement Therapy or HRT) covers a range of hormonal treatments that can reduce menopausal symptoms.
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