International Journal of Innovative Technologies in Social Science · May 12, 2026

MENOPAUSAL HORMONE THERAPY AND DEMENTIA RISK: AN INTEGRATED NEUROVASCULAR AND PRECISION MEDICINE PERSPECTIVE

By Stanek N, Jagiełło A, Pietrzyk P et al.

Background: The relationship between menopausal hormone therapy (MHT) and dementia risk remains controversial. Early observational studies suggested neuroprotective effects, whereas large randomized trials reported neutral or adverse outcomes in older women. These inconsistencies led to the development of the therapeutic window hypothesis, proposing that cognitive effects depend on the timing of therapy initiation relative to menopause onset. Objective: This narrative review aims to critically synthesize contemporary evidence (1990–2025) regarding the association between MHT and dementia risk, integrating randomized controlled trials, longitudinal cohort studies, neuroimaging findings, and mechanistic data within a broader neurovascular and precision medicine framework. Methods: A structured narrative approach was employed to evaluate major clinical trials, epidemiological cohorts, and translational research examining timing of initiation, formulation type, route of administration, vascular risk burden, and genetic modifiers such as APOE genotype. Results: Evidence suggests that initiation of MHT within approximately five years of menopause appears cognitively neutral and may confer modest benefit in selected populations, particularly in the absence of significant cerebrovascular pathology. In contrast, initiation after age 65 or following prolonged hypoestrogenism is associated with increased dementia risk in some randomized trials. Emerging data indicate that formulation, progestogen type, cardiometabolic status, and genetic background modify cognitive trajectories. Conclusions: Current evidence does not support the use of MHT solely for dementia prevention. However, timing and individual risk profiles substantially influence risk–benefit ratios. A precision medicine approach integrating neurovascular health and genetic susceptibility may better explain heterogeneity in observed outcomes and guide individualized clinical decision-making.

doi.org/10.31435/ijitss.2(50).2026.5277 Open access Interventions