A large study found that women who used estrogen-only hormone therapy later in life had a lower risk of Alzheimer’s disease-related brain changes and dementia. The findings were published on August 12, 2026, in Neurology, the medical journal of the American Academy of Neurology.
Researchers emphasized that the study found an association, not a cause-and-effect relationship. The results do not prove that hormone therapy prevents dementia or Alzheimer’s disease.
“These findings help us better understand the relationship between hormone therapy use and various markers of dementia, but more research is needed before we can make recommendations to women about the use of these therapies in relation to brain health,” said study author Dr. Jennifer Bruno of Stanford Medicine. “This study looks back at women who were using hormone therapy decades ago, and the timing and type of use is different from what is currently happening for most women today. Therefore, the results, while informative, may not apply to current treatment standards.”
Study included more than 21,000 women
Researchers analyzed medical data from two large datasets involving 21,462 women who underwent clinical evaluations before death. In one dataset, 728 participants received brain scans or biomarker testing while they were alive. In the second dataset, 2,959 women, with an average age of 82, underwent autopsies so researchers could examine their brains for Alzheimer’s disease pathology.
Participants were followed for approximately three to five years. Their average age at the start of the study was 71.
Among all participants, 1,953 women had used hormone therapy, while 19,509 had not. On average, women in the hormone therapy group began treatment after age 70.
The analysis focused exclusively on estrogen-only hormone therapy. Earlier research has suggested that combined estrogen and progestin therapy may increase dementia risk. Today, estrogen-only therapy is generally prescribed to women who have had a hysterectomy because estrogen can increase the risk of endometrial cancer in women who still have a uterus.
Autopsies found fewer Alzheimer’s disease markers
Women who had used hormone therapy were less likely to show signs of Alzheimer’s disease in their brains after death.
Researchers examined three primary Alzheimer’s disease markers: amyloid beta plaques, tau tangles, and neuritic plaques. Neuritic plaques are amyloid deposits surrounded by damaged nerve cells. The researchers combined these markers into an overall score representing the amount of Alzheimer’s-related brain pathology.
Among women who used hormone therapy, 18% had no evidence of Alzheimer’s disease at autopsy. By comparison, 10% of women who had not used hormone therapy showed no signs of the disease.
At the other end of the spectrum, 40% of women in the hormone therapy group had all three Alzheimer’s disease markers, compared with 51% of women who did not use hormone therapy.
After adjusting for age, education, genetic factors, race, high blood pressure, and other variables, hormone therapy use was associated with a 35% lower likelihood of showing Alzheimer’s disease-related changes at autopsy.
Biomarkers suggested less amyloid buildup
A separate analysis examined biomarker tests collected while participants were alive. Blood and spinal fluid amyloid measurements in women who used hormone therapy were consistent with lower levels of amyloid accumulation in the brain compared with women who had not used the therapy.
Higher levels of amyloid beta in the blood and spinal fluid may indicate that less of the protein has been deposited as plaques in the brain.
Hormone therapy use was also associated with 39% lower odds of a clinical dementia diagnosis. Women who used the therapy were less likely to experience memory problems or declines in their ability to perform daily activities.
Study findings may not reflect current hormone therapy use
A major limitation of the study is that participants used hormone therapy differently from the way it is commonly prescribed today. Dr. Bruno noted that the average age of women who used hormone therapy was 70.
Current medical guidance generally recommends starting hormone therapy during the late 40s or early 50s, when menopause symptoms begin, and discontinuing treatment before age 60 when possible.
“Despite these limitations, our findings provide evidence that the use of estrogen-only hormone therapy in later life is associated with better dementia and brain health outcomes,” Dr. Bruno said.
The National Institute on Aging supported the research.
Source: www.sciencedaily.com