Estrogen-Only Hormone Therapy Linked to Lower Alzheimer’s Risk

A recent study from Stanford, published on August 12 in the journal Neurology, suggests that women using estrogen-only menopausal hormone therapy (MHT) may have a reduced risk of developing Alzheimer’s-related brain changes or dementia.

The research involved analyzing post-mortem data from 21,462 individuals, focusing specifically on 258 women who had reported using estrogen-only MHT compared to about 2,701 women who did not use any MHT.

Scientists examined the brains of these participants for indicators of Alzheimer’s disease, including amyloid plaques and neurofibrillary tangles, both of which are characteristic changes seen in the brains of those with dementia.

Findings indicated that women on estrogen-only therapy — many of whom had previously undergone hysterectomies — demonstrated a 35% lower incidence of Alzheimer’s pathology and a 39% reduced likelihood of developing dementia throughout their lifetime.

In assessments among some living participants, those who used estrogen-only therapy also performed better in memory tests and showed greater independence in daily activities. Biomarkers in both blood and cerebrospinal fluid corroborated these positive results.

The average age of participants in the study was around 70 years. The researchers pointed out that recent developments suggest menopausal hormone therapy may be more beneficial when initiated during or shortly after menopause, hinting that, perhaps, the potential advantages of earlier treatments have been underestimated since most studied women started therapy later in life.

This study’s outcomes diverge from earlier research that found links between menopausal hormone therapy and increased dementia risk. Jennifer Bruno, PhD, one of the study’s authors, noted the recognized neuroprotective effects of estrogen observed in animal models, highlighting its role in redirecting amyloid levels and promoting tau dephosphorylation, both of which are essential in mitigating Alzheimer’s disease features.

Bruno explained, “Estrogen supports synaptic plasticity, lowers neuroinflammation, and maintains the integrity of the blood-brain barrier, helping to clarify the study’s findings of decreased Alzheimer’s pathology among estrogen-only users.”

Senior author Hadi Hosseini emphasized that while significant advances have been made with biomarkers, they may not provide precise details regarding brain damage location or extent. Thus, studying the actual brain remains crucial to understanding Alzheimer’s-related changes.

There are limitations to the study, mainly its observational nature, which means it can only suggest associations rather than enforce a causal link between hormone therapy and decreased risk of Alzheimer’s. Hosseini remarked that variations between users and non-users could be factors that weren’t thoroughly accounted for, including overall health and healthcare interactions.

While these findings are significant, the current clinical guidelines remain unchanged. The researchers stress the importance of conducting well-structured clinical trials to verify these observations and better gauge the cognitive protective effects of menopausal hormone therapy.

As Alzheimer’s disease is the leading cause of dementia in older adults, with women making up about two-thirds of cases, this research opens a dialogue for future investigations into hormone therapy and its impacts on brain health.