A form of hormone therapy used by many women after menopause may be linked to a lower risk of Alzheimer’s disease, according to a large study from Stanford Medicine.
The strongest results were seen in women who used estrogen without the hormone progestin.
Menopause happens when the ovaries greatly reduce their production of hormones such as estrogen. This natural change usually occurs in middle age and can cause hot flashes, sleep problems, vaginal dryness and other symptoms.
Menopausal hormone therapy can replace some of the hormones that decline during this period. Women who still have a uterus are usually given estrogen together with a form of progesterone because estrogen alone can increase the risk of cancer in the lining of the uterus.
Estrogen-only treatment is generally used for women who have had their uterus removed in a hysterectomy. That distinction is important because the new findings apply specifically to estrogen-only therapy and should not automatically be extended to other hormone combinations.
Researchers have debated for decades whether hormone therapy affects the aging brain. Some earlier studies suggested benefits, while others raised concerns that treatment could increase the risk of dementia, leaving patients and doctors with confusing messages.
The Stanford Medicine team took a different approach. Instead of relying only on memory tests or medical diagnoses, the researchers examined what was actually present in women’s brains after death.
Alzheimer’s disease causes characteristic changes in brain tissue. Two of the best-known are amyloid plaques, which are abnormal deposits that collect between nerve cells, and tau tangles, twisted protein structures that build up inside cells.
These changes can begin many years before severe memory problems appear. Although doctors can increasingly estimate Alzheimer’s-related changes using brain scans, blood tests and spinal fluid, examining brain tissue after death remains one of the clearest ways to measure the disease’s physical signs.
The researchers used information from two existing databases containing 21,462 participants. They focused on women who had died and whose brains had been examined for Alzheimer’s-related changes.
Among them were 258 women who had reported using estrogen-only menopausal hormone therapy. Their autopsy results were compared with those of about 2,701 women who had reported never using menopausal hormone therapy.
The researchers measured the amount and location of amyloid plaques and tau tangles. They also considered the density of individual amyloid deposits and combined these observations into measures of Alzheimer’s-related brain damage.
Women who had used estrogen-only therapy showed significantly less Alzheimer’s pathology. Overall, the researchers calculated that estrogen-only therapy was associated with about 35% lower odds of developing the brain changes used to identify Alzheimer’s disease.
Other information supported the autopsy findings. Estrogen-only users had 39% lower odds of receiving a clinical dementia diagnosis during life and also performed better on memory tests and measures of their ability to live independently.
The researchers adjusted their analysis for several major factors that can influence Alzheimer’s risk. These included age, education, race, high blood pressure and APOE4, a gene variant that substantially raises the chance of developing Alzheimer’s disease.
Alzheimer’s is the most common cause of dementia, and women make up about two-thirds of people living with the disease. This difference is partly because women tend to live longer, although hormones and other biological factors may also contribute.
The findings could be relevant to a substantial group of women because hysterectomy is common. By age 60, more than 30% of women have had their uterus removed, according to the researchers, making estrogen-only therapy an option for many menopausal women.
However, the study cannot answer every question about hormone therapy. There were too few autopsied women using estrogen together with progestin for the researchers to reach a reliable conclusion about that treatment.
The analysis also did not include women using estrogen applied through the skin. The results therefore should not be assumed to apply to patches, gels or other topical estrogen products.
The research, led by investigators including senior author Hadi Hosseini and co-lead author Jennifer Bruno, was published August 12, 2026, in the journal Neurology. The authors say it is the first study to connect menopausal hormone therapy with Alzheimer’s-related changes measured directly in a substantial number of autopsied brains.
The results add a new chapter to a long-running medical debate. A major study reported in 2003 found that estrogen combined with progestin increased dementia risk in older women, helping drive a sharp decline in the use of menopausal hormone therapy.
Scientists now increasingly believe that the type of hormone treatment, the age when it begins, the route of administration and a woman’s individual health risks may all influence the outcome. This makes it misleading to treat all forms of menopausal hormone therapy as if they were the same.
The new Stanford study has an important strength because it looked directly at Alzheimer’s pathology rather than relying only on a dementia diagnosis. Its results were also consistent across brain findings, memory performance and clinical dementia outcomes.
But it was an observational study, so it cannot prove that estrogen caused the lower Alzheimer’s risk. Women who choose hormone therapy may differ from nonusers in health, medical care or other ways that are difficult to remove completely through statistical adjustments.
The study therefore does not show that women should start estrogen simply to prevent Alzheimer’s disease. Hormone therapy has benefits and risks that vary between individuals, and decisions should consider menopausal symptoms, age, medical history and other health factors.
Overall, the findings make the old idea that all menopausal hormone therapy is harmful to the brain look too simple. They provide strong reasons for further research, particularly studies that separate estrogen-only treatment from combined therapy and examine when treatment begins.
