Efeitos cardiovasculares da terapia hormonal precoce versus tardia na pós-menopausa: uma revisão sistemática

Abstract

Objective: To evaluate the effects of hormone therapy (HT) on cardiovascular outcomes in postmenopausal women, with emphasis on risk modification by timing of initiation relative to menopause. Methods: Systematic review conducted and reported according to PRISMA guidelines, registered in PROSPERO (CRD420251145132). The search was performed in February 2026 in the MEDLINE/PubMed, Cochrane Library, and Scopus databases, with no restrictions on publication date and language restrictions limited to studies published in Portuguese, English, or Spanish. Only RCTs involving postmenopausal women receiving systemic estrogen alone or combined with progestogen for a period of ≥12 months and reporting cardiovascular outcomes were included. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Of the 1,735 articles identified, 23 RCTs were included, encompassing more than 45,000 women. Early initiation of HT with estrogen alone in women within 10 years of menopause was associated with trends toward reduction in coronary artery disease and mortality, with the most pronounced benefit observed in the 50–59 age group. Late initiation, particularly after 20 or more years, was associated with a significant increase in coronary and cerebrovascular risk. The risk of stroke was consistently elevated across both therapy types, with no modification by age at initiation. Venous thromboembolism risk was increased across all age groups, with greater magnitude for combined therapy. Conclusion: The cardiovascular effects of HT are modulated by timing of initiation and type of therapeutic regimen. A cardiovascular window of opportunity was identified for early initiation with estrogen alone, which does not extend to thromboembolic risk, a transversal contraindication in the oral regimens evaluated, and should not be extrapolated to transdermal formulations with micronized progesterone, whose risk profile is substantially more favorable. Interpretation of findings must account for relevant limitations: the WHI population had a mean age of 63.3 years, exclusively oral formulations with MPA were used, subgroup analyses were predominantly post hoc, and contemporary formulations are not represented. The gap in RCTs with primary clinical endpoints, current formulations, and recently menopausal populations remains critical. These findings reinforce the need for clinical personalization and for new randomized trials.