Journal of Medical & Health Sciences Review · May 25, 2026
Cardiovascular and Cancer Risks Associated with Different Hormone Replacement Therapy Regimens: A Systematic Review and Meta-Analysis (2020–2025 Evidence)
By Imdad DK, Imdad DH, Asim DU et al.
Background: Hormone replacement therapy (HRT) is widely used for the management of menopausal symptoms; however, its safety profile remains controversial due to potential associations with cardiovascular disease and hormone-sensitive cancers. Emerging evidence suggests that these risks vary according to HRT regimen, route of administration, and timing of initiation. This study aimed to systematically evaluate the cardiovascular and oncologic risks associated with different HRT regimens using recent evidence. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Electronic databases including PubMed, google scholar, Scopus, and Research gate were searched for studies published between January 2020 and December 2025. Eligible studies included randomized controlled trials, cohort studies, and case–control studies involving postmenopausal women receiving HRT. Outcomes assessed included coronary artery disease, stroke, venous thromboembolism (VTE), breast cancer, endometrial cancer, and ovarian cancer. Results: A total of 40 studies involving postmenopausal women were included. Early initiation of HRT (≤10 years since menopause) was associated with a neutral or reduced risk of coronary artery disease (HR 0.92; 95% CI 0.84–1.01), whereas late initiation (>10 years) increased risk (HR 1.21; 95% CI 1.08–1.36). HRT use was associated with a modest increase in stroke risk (HR 1.14; 95% CI 1.05–1.24). Venous thromboembolism risk was significantly elevated with oral estrogen (HR 1.62; 95% CI 1.41–1.86) but not with transdermal formulations (HR 1.08; 95% CI 0.94–1.24). Combined estrogen–progestin therapy was associated with increased breast cancer risk (HR 1.27; 95% CI 1.18–1.37), while estrogen-only therapy significantly increased endometrial cancer risk (HR 1.89; 95% CI 1.55–2.31). A modest increase in ovarian cancer risk was also observed (HR 1.11; 95% CI 1.02–1.21). Conclusion: Cardiovascular and cancer risks associated with HRT vary significantly according to regimen type, route of administration, and timing of initiation. Transdermal estrogen and individualized treatment strategies appear to offer a more favorable safety profile. These findings support a personalized approach to HRT to optimize therapeutic benefits while minimizing adverse outcomes.