Risk of recurrence in women with venous thromboembolism related to estrogen-containing contraceptives: Systematic review and meta-analysis

J Thromb Haemost. 2022 May;20(5):1158-1165. doi: 10.1111/jth.15661. Epub 2022 Feb 13.


Background: The risk of recurrence after a venous thromboembolism (VTE) related to estrogen-containing contraceptives is a key driver to guide anticoagulant treatment decisions.

Objective: To estimate the incidence rate of recurrent VTE after discontinuation of anticoagulant treatment in women with a first episode of VTE related to estrogen-containing contraceptives.

Methods: Embase, MEDLINE, and the CENTRAL were searched from 1 January 2008 to 27 May 2021 for prospective and retrospective studies reporting on recurrence after a first VTE related to estrogen-containing contraceptives. Risk of bias was assessed using QUIPS tool. Recurrence rates per 100 patient-years were pooled using Knapp-Hartung random-effects meta-analysis. Incidence rates were reported separately based on study follow-up duration (≤1 year, 1-5 years, and >5 years) and for several subgroups.

Results: A total of 4,120 studies were identified, of which 14 were included. The pooled recurrence rate was 1.57 (95%-CI: 1.10-2.23; I2 = 82%) per 100 patient-years. Recurrence rates per 100 patient-years were 2.73 (95%-CI: 0.00-3643; I2 = 80%) for studies with ≤1 year follow-up, 1.35 (95%-CI: 0.68-2.68; I2 = 44%) for studies with 1-5 years follow-up, and 1.42 (95%-CI: 0.84-2.42; I2 = 78%) for studies with >5 years follow-up.

Conclusion: Among women with VTE associated with estrogen-containing contraceptives, the risk of recurrence after stopping anticoagulation is low, which favors short-term anticoagulation. Large prospective studies on VTE recurrence rates and risk factors after stopping short-term anticoagulants are needed.

Keywords: contraceptive agents; estrogens; systematic review; thrombosis; women.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects
  • Contraceptives, Oral, Hormonal / adverse effects
  • Estrogens / adverse effects
  • Female
  • Humans
  • Male
  • Prospective Studies
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Venous Thromboembolism* / chemically induced
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / epidemiology


  • Anticoagulants
  • Contraceptives, Oral, Hormonal
  • Estrogens