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

Natalia Stanek; Aleksandra  Jagiełło; Piotr Pietrzyk; Beata Szreder; Patrycja Krawczyk; Joanna Ślusarczyk; Maja Łapaj; Zuzanna Noweta; Milena Lewicka; Tamara Chodań

doi:10.31435/ijitss.2(50).2026.5277

Authors

Natalia Stanek Hospital of the Ministry of Interior and Administration in Katowice, Katowice, Poland https://orcid.org/0009-0009-5745-5253
Aleksandra Jagiełło Mazovian Bródno Hospital in Warsaw, Warsaw, Poland https://orcid.org/0009-0005-6310-6755
Piotr Pietrzyk Mazovian Bródno Hospital in Warsaw, Warsaw, Poland
Beata Szreder Medical University of Gdansk, Gdansk, Poland https://orcid.org/0009-0008-7876-2159
Patrycja Krawczyk Provincial Hospital in Kielce, Kielce, Poland https://orcid.org/0009-0001-0536-4570
Joanna Ślusarczyk Provincial Hospital in Kielce, Kielce, Poland https://orcid.org/0009-0008-6405-5963
Maja Łapaj Hospital of the Ministry of Interior and Administration in Katowice, Katowice, Poland https://orcid.org/0009-0006-8285-6997
Zuzanna Noweta Collegium Medicum of the Nicolaus Copernicus University in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0009-8086-8101
Milena Lewicka Medical University of Gdansk, Gdansk, Poland https://orcid.org/0009-0006-2919-9537
Tamara Chodań Collegium Medicum of the Nicolaus Copernicus University in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0001-5891-7925

DOI:

https://doi.org/10.31435/ijitss.2(50).2026.5277

Keywords:

Hormone Replacement Therapy (MeSH), Menopause, Dementia, Alzheimer Disease, Cognition, Cerebrovascular Disorders

Abstract

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.

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