A large Stanford study published in Neurology found that women who used estrogen-only menopausal hormone therapy (MHT) had fewer Alzheimer’s-related brain changes and lower rates of dementia compared with women who did not use MHT.
Researchers analyzed post-mortem brain data from 21,462 participants, including 258 women who reported using estrogen-only therapy and approximately 2,701 women who reported no menopausal hormone therapy use.
Estrogen-only therapy associated with fewer Alzheimer’s markers
The researchers examined brain tissue for key signs of Alzheimer’s disease, including amyloid plaques, neurofibrillary tangles, and amyloid plaque density.
Women who used estrogen-only therapy, most of whom likely had undergone hysterectomies, showed a 35% lower likelihood of Alzheimer’s pathology and 39% lower odds of dementia over their lifetime.
Among living participants, estrogen-only users also showed stronger performance on memory tests and better ability to function independently. Blood and cerebrospinal fluid biomarkers supported these findings.
Study explores estrogen’s potential brain benefits
Researchers noted that recent evidence suggests menopausal hormone therapy may provide greater benefits when started during or shortly after menopause. Since participants in the study generally began treatment at older ages, the findings may underestimate the potential impact of earlier therapy.
The results challenge previous research that associated menopausal hormone therapy with increased dementia risk. Researchers suggested that estrogen may have protective effects in the brain by influencing amyloid processing, supporting synaptic function, reducing inflammation, and maintaining blood-brain barrier health.
Researchers caution that more studies are needed
The study authors emphasized that the findings show an association rather than proving that estrogen therapy directly prevents Alzheimer’s disease. Because the research was observational, differences between hormone therapy users and non-users, such as overall health or access to healthcare, could have influenced the results.
Researchers also noted that while blood and cerebrospinal fluid biomarkers have improved Alzheimer’s detection, examining the brain directly provides a clearer picture of the location and extent of disease-related changes.
Findings do not change current hormone therapy guidance
Experts said the results provide important evidence in an ongoing debate about the relationship between menopausal hormone therapy and brain health, but they do not change current clinical recommendations.
Researchers called for additional clinical trials that follow women before, during, and after menopause to better understand how hormone therapy may affect cognitive health and Alzheimer’s risk.
