Menopausal Hormone Therapy Linked to Faster Tau Buildup

A new study from Mass General Brigham researchers has found faster accumulation of tau—a key indicator of Alzheimer’s disease—in the brains of women over the age of 70 who took menopausal hormone therapy (HT) more than a decade before. Results, which are published in Science Advances, could help inform discussions between patients and clinicians about Alzheimer’s disease risk and HT treatment.

While the researchers did not see a significant difference in amyloid beta accumulation, they did find a significant difference in how fast regional tau accumulated in the brains of women over the age of 70, with women who had taken HT showing faster tau accumulation in specific regions of the brain. This difference was not seen in women younger than 70.

“Approximately a quarter of currently postmenopausal women who are 70 years and older have a history of HT use and have now entered a critical age of risk for Alzheimer’s disease,” said senior author Rachel F. Buckley, PhD, of the Department of Neurology at Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system. “Our findings add to the evidence that delaying initiation of HT, especially in older women, could lead to worse Alzheimer’s outcomes.”

The study, which was led by first author Gillian T. Coughlan, PhD, of MGH’s Department of Neurology, compared brain imaging from 73 women who had used hormone therapy an average of 14 years prior and 73 age-matched women who had not. Participants were between ages 51 and 89 at the beginning of the study. Participants had PET scans for amyloid beta over a mean 4.5-year period and for tau over a 3.5-year period.

The authors note that they cannot definitively conclude whether the influence of chronological age is due to changes in guidelines on HT prescribing or simply due to a higher tau-PET signal typically observed at more advanced ages. Current clinical guidance is that HT should be initiated within 10 years following a woman’s age at menopause to avoid adverse effects.

“Our data indicate that HT may influence tau accumulation as a function of age, with implications for cognitive decline,” said Coughlan. “We hope that our study will help to inform AD risk discussions relating to women’s reproductive health and treatment.”

Reference: Coughlan GT, Rubinstein Z, Klinger H, et al. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease. Sci Adv. 2025;11(10):eadt1288. doi: 10.1126/sciadv.adt1288

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