Is Vaginal Estrogen Treatment Associated with Risk of Thrombosis in Postmenopausal Women? A Scoping Review

Abstract Although the thromboembolic risk associated with oral estrogen is recognized, the risk profile of vaginal estrogen treatment remains inconclusive. This scoping review aims to explore available evidence on the association between vaginal estrogen treatment in postmenopausal women and the risk of thrombosis. We conducted a systematic search of PubMed and Embase, investigating vaginal estrogen treatment and thrombosis, for all records up to May 21, 2025. The process was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) and a preregistered protocol (osf.io/hgecd). We excluded systemic estrogen treatments, contraception, fertility treatments, gender-affirming therapies, and hormone treatments other than estrogen. Eligible study designs included clinical trials, randomized controlled trials, observational, case–control, and cohort studies. The search identified 866 articles, whereof 8 were eligible. Manual searching through citations and references yielded 3 additional studies, resulting in 11 included articles, all observational. One study reported a reduced risk of recurrent myocardial infarction (MI) following discontinuation of vaginal estrogen treatment (adjusted hazard ratio [aHR]: 0.54; 95% confidence interval [CI]: [0.34–0.86]). Remaining studies found no thrombosis risk in vaginal estrogen users. For venous thromboembolism (n = 6), effect estimates ranged from null to reduced risk (aHRs: 0.68 [0.36–1.28], to 1.06 [0.58–1.93]), similar for MI (n = 5; aHRs: 0.52 [0.31–0.85] to 0.83 [0.77–0.89]) and stroke (n = 6, aHRs: 0.68 [0.62–0.70] to 0.96 [0.93–0.99]). This scoping review, including studies of generally moderate to high methodological quality, indicates no increased risk of thrombosis associated with vaginal estrogen use in postmenopausal women. Further prospective, high-quality clinical trials, including high-risk populations and women with prior thrombosis, are warranted.