Recurrent venous thromboembolism and vaginal estradiol in women with prior venous thromboembolism: A nested case–control study

Objectives: Whether vaginal estradiol use is associated with an increased risk of recurrent venous thromboembolism (VTE) in women with prior VTE is unknown. We sought to evaluate the association between vaginal estradiol use and recurrent VTE in women with prior VTE. Methods: We performed a nationwide nested case–control study among 44 024 women aged ≥45 years who developed a first VTE without a history of vaginal estrogen use prior to VTE diagnosis. Cases with recurrent VTE were matched 1:2 on birth year with controls using incidence density sampling. Exposure to vaginal estradiol tablets was categorized into current use (0–2 months before index), prior use (2–24 months before index) and past use (more than 24 months prior to index). Results: We identified 5066 cases and 10 127 age-matched controls. In fully adjusted analysis vaginal estrogen was not associated with recurrent VTE with a hazard ratio of 0.75, p =.07 for current use, 0.83, p =.13 for prior use, and 1.24, p =.06 for past use. Conclusion: Use of vaginal estradiol tablets in women with prior VTE was not associated with an increased rate of recurrent VTE. Our study indicates that vaginal estradiol therapy is unlikely to increase risk of recurrent VTE in women with prior VTE.