Estrogen-only hormone therapy linked to lower dementia risk

Clinical takeaway: Estrogen-only menopausal hormone therapy was associated with lower odds of dementia, less Alzheimer’s disease pathology, and lower amyloid burden, adding to evidence that estrogen exposure may influence brain health later in life.

The relationship between menopausal hormone therapy and dementia has long been uncertain, with prior studies producing conflicting results. New data linking estrogen-only therapy not only to clinical dementia but also to Alzheimer’s disease pathology and biomarkers add another piece to the debate over estrogen’s potential effects on the aging brain.

Researchers analyzed two large Alzheimer’s research cohorts of women aged 50 and older, comparing those who reported estrogen-only menopausal hormone therapy with nonusers. The study examined several complementary measures of Alzheimer’s disease, including autopsy findings, blood and cerebrospinal fluid biomarkers, and clinical outcomes.

At autopsy, estrogen-only therapy was associated with 35% lower odds of greater Alzheimer’s disease pathology. The pathology assessment incorporated amyloid-beta plaques, tau tangles, and neuritic plaques. Biomarker analyses pointed in the same direction, with hormone therapy use associated with measures indicating lower amyloid pathologic burden in plasma and cerebrospinal fluid.

The association extended to clinical outcomes. Estrogen-only therapy was associated with 39% lower odds of a dementia diagnosis and 33% lower odds of symptoms of memory or functional decline.

The study cannot establish that estrogen protects against dementia, and its applicability to current menopausal hormone therapy remains uncertain because treatment practices have changed substantially over time. Still, the consistency across neuropathology, biomarkers, and clinical outcomes strengthens the rationale for further study.

“While these findings help us better understand the relationship between hormone therapy use and various markers of dementia, more research needs to be done before we can make recommendations to women about their use of these therapies in relation to their brain health,” said study author Jennifer Bruno, PhD, of Stanford Medicine.

Source: Bruno J, et al. (2026 Aug 12) Neurology. Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology