Women who used estrogen-only menopausal hormone therapy (MHT) were less likely to develop Alzheimer’s-related brain changes or dementia, according to a large Stanford study published Aug. 12 in Neurology.
The researchers analyzed post-mortem data from 21,462 participants, comparing 258 women who reported estrogen-only MHT use with approximately 2,701 women who reported no MHT use.
The researchers examined the brains for signs of Alzheimer’s disease, including amyloid plaques, neurofibrillary tangles and amyloid-plaque density. Plaques and tangles are two hallmark brain changes associated with the common dementia.
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The women who took estrogen-only therapy — most of whom had likely undergone hysterectomies — were found to have a 35% lower chance of Alzheimer’s pathology and 39% lower odds of dementia over a lifetime.
Among some living participants, estrogen-only users also performed better on memory testing and were better able to function independently, the study found. Biomarkers in blood and cerebrospinal fluid supported these results.
The participants averaged 70 years of age.
Recent research indicates that menopausal hormone therapy may offer greater benefits when started during or shortly after menopause, the researchers noted.
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Because the women in the study were generally older when they began treatment, the results may actually understate the potential benefits of earlier therapy.
These findings appear to contradict prior studies that linked menopausal hormone therapy to increased dementia risk.
"Estrogen has well-described neuroprotective effects in animal models," co-author Jennifer Bruno, PhD, an instructor in psychiatry and behavioral sciences, told Fox News Digital.
"Estrogen 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."
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"Additionally, estrogen supports synaptic plasticity, reduces neuroinflammation and supports blood brain barrier integrity. So, finding less AD pathology in estrogen-only users was consistent with this mechanism."
Memory can be impacted by many different conditions, which means clinical diagnoses can sometimes be unreliable, the researchers noted.
"Although there’s been great progress with bloodborne and cerebrospinal fluid biomarkers, they don’t tell you the amount and precise location of the brain damage," said senior author Hadi Hosseini, Ph.D., an associate professor of psychiatry and behavioral sciences at Stanford.
"By looking 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."
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The study did have some limitations, according to the researchers. As it was observational, it could only show an association but could prove that the hormone therapy reduced Alzheimer’s risk.
"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 told Fox News Digital. "We worked hard to adjust for known confounders and to account for who does and doesn't come to autopsy, but observational data can only take you so far."
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Alzheimer’s disease is the leading cause of dementia among older adults, with women comprising about two-thirds of diagnoses.
While the study findings don’t change current clinical recommendations, Hosseini said they highlight the need for well-designed clinical trials to confirm these observations and to determine whether menopausal hormone therapy has a protective cognitive effect.
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"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," Bruno added.
"We need prospective, biomarker-based trials that follow women before, during and after menopause to understand the effects of MHT on brain health."
The study was funded by the National Institutes of Health.
