Key Takeaway:
- Estrogen-only therapy was linked to 35% lower odds of Alzheimer’s-related brain pathology in women with hysterectomies.
- The study does not prove prevention; it found an association based on brain autopsy findings.
- Researchers call for more studies examining hormone type, timing, and duration around menopause.
Older women who used estrogen-only hormone therapy after menopause had 35% lower odds of Alzheimer’s disease-related brain pathology than those who did not, according to a study of more than 5,000 women with hysterectomies whose brains were examined after death.
Study Links Estrogen Use to Lower Brain Pathology
Researchers analyzed medical records and autopsy findings to examine whether estrogen therapy was associated with Alzheimer’s disease pathology. The study focused on women who had undergone hysterectomy, allowing researchers to examine estrogen therapy without the addition of progesterone, which is generally used to protect the uterus.
Women who received estrogen-only therapy had lower odds of having Alzheimer’s hallmarks, including amyloid plaques, in their brains compared with women who did not receive estrogen.
The researchers say the use of brain autopsy findings strengthens the study because the outcomes are based on physical evidence of disease rather than clinical assessments alone.
“Previous studies used cognitive decline or clinical ratings of dementia,” Jennifer Bruno, an instructor in psychiatry at Stanford University and a study co-author, said. Those measures are important, she said, but they do not provide a definitive diagnosis of Alzheimer’s disease.
The findings are consistent with earlier research suggesting that estrogen may influence brain aging. Estrogen receptors are present throughout the brain, and estrogen levels fall sharply during menopause.
Findings Do Not Prove Estrogen Prevents Alzheimer’s
The results do not establish that estrogen therapy prevents Alzheimer’s disease, researchers cautioned. The study is observational, meaning it identifies an association between hormone use and brain pathology rather than proving that estrogen caused the lower risk.
“Data are bringing awareness to the fact that maybe we need to reconsider some of the previous findings,” Hadi Hosseini, an associate professor of psychiatry at Stanford and a study co-author, said.
Earlier research has produced conflicting results. The landmark Women’s Health Initiative, whose initial findings were released in 2002, raised concerns about hormone therapy after researchers reported increased risks associated with certain hormone regimens, including dementia.
That research primarily involved older postmenopausal women and examined different hormone formulations. The new study’s focus on estrogen-only therapy in women who had undergone hysterectomy makes direct comparisons difficult.
Researchers also note that the study did not establish when participants began estrogen therapy, which formulation they used, or how long they continued treatment.
Researchers Call for Longer-Term Studies
The researchers say future studies should examine the timing, formulation and duration of hormone therapy. Those factors could help determine whether there is a period around menopause when estrogen may have different effects on Alzheimer’s-related brain changes.
Bruno said future research could follow women from perimenopause through menopause while tracking Alzheimer’s biomarkers in blood and spinal fluid and changes visible on brain imaging.
Such studies could provide stronger evidence about whether estrogen therapy affects the development of Alzheimer’s pathology and whether timing influences its potential benefits.
The findings add to growing research into why Alzheimer’s disease affects women disproportionately and whether changes in hormones around menopause contribute to later brain disease. However, the evidence is not sufficient to recommend estrogen therapy specifically for Alzheimer’s prevention.
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