Women using estrogen-only menopausal hormone therapy may experience a 35% reduction in Alzheimer’s pathology and a 39% decrease in dementia risk, according to a recent Stanford study.
A recent study conducted by researchers at Stanford University suggests that women who utilize estrogen-only menopausal hormone therapy (MHT) may have a significantly lower risk of developing Alzheimer’s disease and related dementia. Published on August 12 in the journal Neurology, the study analyzed post-mortem data from 21,462 participants, focusing on 258 women who reported using estrogen-only MHT compared to approximately 2,701 women who did not use any form of MHT.
The researchers examined the brains of the participants for indicators of Alzheimer’s disease, including amyloid plaques and neurofibrillary tangles, which are two hallmark changes associated with the condition. The findings revealed that women who had undergone estrogen-only therapy had a 35% lower likelihood of exhibiting Alzheimer’s pathology and a 39% reduced risk of developing dementia over their lifetimes.
Among some living participants, those who used estrogen-only therapy performed better on memory tests and demonstrated greater independence in daily activities. Biomarkers found in blood and cerebrospinal fluid corroborated these results, suggesting a potential protective effect of estrogen on cognitive health. The average age of participants in the study was 70 years.
The researchers noted that recent studies indicate menopausal hormone therapy may yield greater benefits when initiated during or shortly after menopause. However, since many women in this study began treatment at an older age, the results may underrepresent the potential advantages of starting therapy earlier.
These findings challenge previous research that associated menopausal hormone therapy with an increased risk of dementia. Co-author Jennifer Bruno, PhD, an instructor in psychiatry and behavioral sciences at Stanford, explained, “Estrogen has well-described neuroprotective effects in animal models. It plays a role in shifting amyloid toward the non-amyloidogenic pathway and promoting tau dephosphorylation—both amyloid and tau are hallmarks of Alzheimer’s disease.”
Bruno further elaborated that estrogen supports synaptic plasticity, reduces neuroinflammation, and maintains the integrity of the blood-brain barrier. Consequently, the observed reduction in Alzheimer’s pathology among estrogen-only users aligns with these mechanisms.
Despite these promising findings, the study is not without limitations. As an observational study, it can only establish an association rather than a direct cause-and-effect relationship between hormone therapy and reduced Alzheimer’s risk. Senior author Hadi Hosseini, PhD, an associate professor of psychiatry and behavioral sciences at Stanford, acknowledged that “it’s possible that women who used hormone therapy differed from non-users in ways we couldn’t fully measure, such as baseline health status or engagement with healthcare.”
Hosseini emphasized that while the research team made efforts to adjust for known confounding factors, observational data has inherent limitations. “By looking at where the actual damage is done—the brain—you can see where the Alzheimer’s-associated defining features are and how many of them are there,” he added.
Alzheimer’s disease remains the leading cause of dementia among older adults, with women accounting for approximately two-thirds of diagnoses. Although the study’s findings do not alter current clinical recommendations, Hosseini underscored the necessity for well-designed clinical trials to validate these observations and determine whether menopausal hormone therapy indeed has a protective effect on cognitive health.
Bruno reiterated the importance of further research, stating, “These results add meaningful, first-of-their-kind pathological evidence to a genuinely controversial area—but they are a signal for further study, not a reason to start or stop MHT for brain health.”
She called for prospective, biomarker-based trials that follow women before, during, and after menopause to better understand the effects of MHT on brain health. The study was funded by the National Institutes of Health.
According to Fox News, the implications of this research could pave the way for new approaches in managing cognitive health in postmenopausal women.