CARDIOVASCULAR SAFETY OF MENOPAUSAL HORMONE THERAPY: INFLUENCE OF ADMINISTRATION ROUTE, FORMULATION AND WINDOW OF OPPORTUNITY

Abstract

Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms, but its cardiovascular effects depend on clinical profile, timing of initiation, formulation, and route of administration. This review analyzed the cardiovascular safety of MHT in peri- and postmenopausal women. An integrative review was conducted and reported in a structured manner according to PRISMA 2020, using PubMed/MEDLINE and SciELO and covering publications from August 18, 2021, to August 18, 2026. The search identified 569 records; after removal of one duplicate, screening, and full-text assessment, 27 publications were included. Findings were heterogeneous: oral combined regimens and tibolone showed more consistent signals for venous thromboembolism, ischemic disease, and stroke in cohort studies, whereas transdermal therapy did not demonstrate universal cardiovascular protection. Trials and analyses from the Women’s Health Initiative suggested cardiovascular neutrality in symptomatic women aged 50–59 years, while risk increased at older ages. MHT should therefore not be prescribed for primary cardiovascular prevention; when indicated for symptoms, it requires individualized risk stratification, shared decision-making, and careful selection of dose, route, and progestogen.