Use of hormone therapy later in life was associated with a lower risk of developing dementia, according to a study published August 12, 2026, in Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that hormone therapy prevents dementia; it only shows an association.
“While these findings help us better understand the relationship between hormone therapy use and various markers of dementia, more research needs to be done before we can make recommendations to women about their use of these therapies in relation to their brain health,” said study author Jennifer Bruno, PhD, of Stanford Medicine in Stanford, California. “This study looked back at women who were using hormone therapy decades ago with the timing and type of use differing from what is current practice for most women today, so the results are informative, but they may not apply to today’s standards.”
For the study, researchers examined medical records from two large data sets. In total, the study reports data from 21 462 female participants from both groups who had clinical tests taken while they were living. A total of 728 participants from one data set completed brain scans or biomarker tests while they were living and 2959 participants from the other data set had autopsies after death, at an average age of 82, to look for signs of Alzheimer’s disease. Across both data sets, participants were followed for approximately three to five years, starting at an average age 71.
Of the total participants, 1953 participants took hormone therapy and 19 509 participants did not take hormone therapy. Those who used hormone therapy started using it when they were over age 70, on average. The researchers looked only at participants who took oestrogen-only therapy, since previous studies had indicated that oestrogen plus progestin combination therapy may increase the risk of dementia. In current standard practice, oestrogen-only therapy is prescribed only for those who have undergone a hysterectomy due to the risk of endometrial cancer.
Among the group with autopsy information available, participants who had taken hormone therapy were less likely to have signs of Alzheimer’s disease in their brains than those who had not taken hormone therapy. The autopsy assessment used a composite score that measures three hallmarks of Alzheimer’s disease: amyloid-beta plaques, tau tangles and neuritic plaques, which are amyloid plaques surrounded by damaged nerve cells.
Of those who had taken hormone therapy, 18% had no signs of Alzheimer’s disease in their brains at autopsy, compared to 10% of those who had not taken the therapy, and 40% of hormone therapy users had all three signs of Alzheimer’s disease, compared to 51% of those who had not taken the therapy. After adjusting for age, education, genetics, race and hypertension, researchers found that participants who took hormone therapy had 35% lower odds of signs of Alzheimer’s disease at autopsy when compared to those who did not take hormone therapy.
In a separate analysis using biomarker tests performed when women were living, those who used hormone therapy had levels of amyloid biomarkers in their blood and spinal fluid that indicated less amyloid buildup in the brain compared to women who did not take hormone therapy. Specifically, higher levels of amyloid-beta protein in blood and spinal fluid suggest that less of this protein was being deposited as plaques in the brain.
Finally, use of hormone therapy was also associated with 39% lower odds of receiving a clinical diagnosis of dementia and less risk of showing symptoms of memory problems or decline in functional abilities.
Bruno noted that the study participants who used hormone therapy had an average age of 70, which differs from current standard practice of starting hormone therapy usually in the late 40s to early 50s and stopping it before age 60.
“Despite these limitations, our findings provide evidence of an association between use of oestrogen-only hormone therapy during later life and better outcomes on dementia and brain health,” Bruno said.
Source: American Academy of Neurology
