A NEW study has demonstrated that menopausal hormone therapy (MHT) impacts brain health in nuanced ways, influenced by age, duration of use, and past surgical history, requiring personalised clinical approaches.
MHT is widely prescribed to alleviate menopausal symptoms, often believed to protect the brain and lower Alzheimer’s disease risk. However, the evidence has been inconsistent, prompting this comprehensive study to investigate the association between MHT and brain health markers using data from 19,846 women in the UK Biobank. By analysing brain MRI scans, the study examined ‘brain age gap’—the difference between chronological and brain age—hippocampal volumes, and other brain health proxies. Factors such as genetic predisposition, type of MHT, and surgical history were also considered.
The study found that current MHT users exhibited a higher brain age gap and smaller hippocampal volumes compared to never-users. Interestingly, past MHT users showed no significant differences in brain age or hippocampal volume relative to never-users. Longer MHT use and stopping later in life were associated with greater brain age gaps. Women who underwent hysterectomy or oophorectomy showed lower brain age gaps while on MHT compared to those without such surgical histories. Importantly, no significant differences emerged from variations in MHT type, dosage, or genetic factors, including the Alzheimer’s-associated APOE ε4 gene.
These findings highlight the complexity of MHT’s effects on brain health. While adverse effects observed in current users were modest, they underscore the need for a tailored approach to MHT, accounting for individual factors such as surgical history and duration of use. The absence of strong neuroprotective or severe adverse effects suggests that timing and personal medical history play critical roles in determining outcomes.
Given the cross-sectional design of this study, causality cannot be inferred. Future longitudinal studies are essential to map the long-term impact of MHT on brain health, providing women and clinicians with robust data to guide decisions. Precision medicine must be central to MHT use to ensure optimal outcomes in female brain health.
Reference
Barth C et al. Menopausal hormone therapy and the female brain: leveraging neuroimaging and prescription registry data from the UK Biobank cohort. ELife. 2024;13:RP99538.
