Alzheimer Disease Risk Found Related to Timing of Hormone Replacement Therapy in Post-Menopausal Patients

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A new meta-analysis research presented at the meeting of the American Neurological Association showed that timing of hormone replacement therapy for post-menopausal patients can affect risk of developing Alzheimer disease.¹ The study found that beginning hormone replacement therapy within 5 years of menopause can lower risk of Alzheimer development by 20 to 32%, and beginning hormone therapy at age 65 or later can increase the risk by up to 38%.

The meta-analysis included over 50 clinical trials and observational studies and compared women using hormone replacement therapy to a placebo/nontreatment group. The analysis looked at Alzheimer disease progression based on blood tests and brain imaging scans, studying the disease progression from initial mild cognitive impairment onward. The average age of individuals in these trials was 51. Overall, the analysis showed a 38% increase in risk of Alzheimer disease in women who began hormone replacement therapy at age 65 or older. The increased risk effect was particularly noticeable in women whose hormone therapy included progestin. Utilizing 45 observational studies, the meta-analysis found a 22% reduced risk of developing Alzheimer disease in women who started hormone replacement therapy nearer to the time of their menopause. From both groups of clinical and observational studies, investigators determined that individuals who started hormone replacement therapy within 5 years of beginning menopause had a 32% lower risk of developing Alzheimer disease.

Researchers indicated that hormone replacement therapy may be useful because it can provide the benefits of estrogen when the natural estrogen levels are dropping in menopause. With sustained estrogen, which is considered to assist in neural communications, inflammation may decrease and protect against cell damage that can lead to Alzheimer disease. On the other hand, if individuals start an estrogen hormone replacement regimen 10 or more years after menopause, inflammation may increase or place stress on the brain’s blood vessels due to potential early signs of Alzheimer disease like reduced blood flow or clumping of proteins.

“Starting hormone replacement therapy early may give the brain some protection, but if a woman already has Alzheimer’s or memory problems, hormone therapy won’t slow them down,” said FNU Vaibhav, MBBS, from Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, in a press release. “It’s like watering a plant: it helps when the plant is growing, but if it’s already wilting, it might be too late.”

Hormone therapy in this context is utilized by women post-menopause, usually to treat symptoms like hot flashes and sleep disturbances. Common forms include administration of estrogen alone, a combination of estrogen and progestin (synthetic progesterone), or estrogen and a selective estrogen receptor modulator. Hormone replacement therapies are often administered in pill or patch form, and are currently used by around 5% of women in the US.²

“The evidence isn’t strong enough to suggest hormone replacement therapy should be taken to prevent Alzheimer’s. However, if a woman is planning to use it for menopause symptoms, starting soon after menopause might give her brain some protection against Alzheimer’s disease later,” added Vaibhav. “She should talk to her doctor about stopping it after a few years to avoid raising her risk. And women should not start hormone replacement therapy in their 60s or 70s to protect their brain because it might do more harm than good.”

References

1. Timing of hormone replacement therapy may influence Alzheimer’s disease risk, study suggests. Press release. September 15, 2025. Accessed September 15, 2025. https://www.newswise.com/articles/timing-of-hormone-replacement-therapy-may-influence-alzheimer-s-disease-risk-study-suggests/?sc=dwhr&xy=5013482 

2. Anderer S. Only about 5% of US women now use menopausal hormone therapy. JAMA. 2024;332(21):1779.