An NIH-funded study found that women over the age of 70 who used menopausal hormone therapy had more accumulation of tau—a protein linked to Alzheimer’s disease—in their brains than older women who had not used hormone therapy. 

Led by Rachel Buckley, Ph.D., a 2022 NIH Director’s New Innovator Award recipient at Massachusetts General Hospital in Boston, the study suggests that timing and age at exposure to hormone therapy may play a role in Alzheimer’s disease risk.

Researchers followed 146 women ages 51 to 89. Half of the study participants had used hormone therapy and half had not. The researchers used positron emission tomography (PET) to scan the brains of participants to look for Alzheimer’s disease markers. These markers included accumulation of tau and accumulation of amyloid-beta, another hallmark of Alzheimer’s disease. 

In women over 70, hormone therapy users had faster tau accumulation in the brain compared to non-users. Tau buildup was localized to certain memory-related brain regions and was also linked to subsequent cognitive decline. The researchers did not see the same link between hormone therapy and tau buildup in women under age 70. They also did not observe significant differences in amyloid-beta accumulation between hormone therapy users and non-users.

According to the authors, the findings are consistent with current treatment guidelines around menopausal hormone therapy use, which recommend that women only use hormone therapy if they are within about 10 years of their menopause onset and not later down the line. The findings also contribute to a growing body of literature exploring the complex connections between hormones and Alzheimer’s disease risk. This study could help inform discussions between patients and clinicians about the potential long-term effects of hormone therapy on brain health.

Reference: Coughlan GT, Rubinstein Z, Klinger H, Lopez KA, Hsieh S, Boyle R, Seto M, Townsend D, Mayblyum D, Thibault E, Jacobs HIL, Farrell M, Rabin JS, Papp K, Amariglio R, Baker S, Lois C, Rentz D, Price J, Schultz A, Properzi M, Johnson K, Sperling R, Buckley RF. Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer's disease. Sci Adv. 2025 Mar 7;11(10):eadt1288. doi: 10.1126/sciadv.adt1288.