Venous Thromboembolism in Women on Estrogen Therapy: Presentation, Management, and Outcomes in the RIETE registry

Combined oral contraceptives (COC) increase venous thromboembolism (VTE) risk nearly fivefold. Their widespread use translates into a substantial number of VTE events in otherwise healthy young women. However, data on estrogen-associated VTE remain limited. We used data from the RIETE registry (2011-2024), including non-cancer patients <50 years with acute VTE. We analyzed presentation, management, and outcomes in women with estrogen-associated VTE compared with men and women with non-estrogen-associated VTE. Among 13,418 patients, 2,786 women experienced VTE during estrogen therapy. They were younger (mean age+/-SD, 32+/-9 years) than men (39+/-8; p<0.001) and other women (38+/-8; p<0.001). Pulmonary embolism occurred in 1,636 (59%) and unusual site VTE in 72 (2.6%). In 74% of estrogen-associated VTE cases, no additional transient risk factors were present. Estrogen therapy was discontinued in 92% of cases at diagnosis. Median anticoagulation duration was 6 months (IQR 4-9). Bleeding during anticoagulation was more frequent in women with estrogen-associated VTE (8.70 per 100 patient-years; 95% CI, 7.09-10.6) and women with non-estrogen-associated VTE (11.8; 95% CI, 10.0-13.7) than in men (5.46; 95% CI, 4.64-6.39; p<0.05), largely owing to uterine bleeding. After stopping anticoagulation, recurrence was lowest in women with estrogen-associated VTE (2.07 per 100 patient-years; 95% CI, 1.57-2.68) compared with men (8.70; 95% CI, 7.75-9.73; p<0.001) and other women (5.05; 95% CI, 4.16-6.07; p<0.001). Women with VTE during estrogen therapy are younger. Bleeding during anticoagulation is more frequent in women than in men. Women with estrogen therapy-associated VTE have a low recurrence risk in the first year after stopping anticoagulation.