A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception

Int J Gynaecol Obstet. 2018 Jun;141(3):287-294. doi: 10.1002/ijgo.12455. Epub 2018 Feb 22.


Background: Combined oral contraceptives (COCs) containing various progestogens could be associated with differential risks for venous thromboembolism (VTE).

Objective: To evaluate the comparative risks of VTE associated with the use of low-dose (less than 50 μg ethinyl estradiol) COCs containing different progestogens.

Search strategy: PubMed and the Cochrane Library were searched from database inception through September 15, 2016, by combining search terms for oral contraception and venous thrombosis.

Selection criteria: Studies reporting VTE risk estimates among healthy users of progestogen-containing low-dose COCs were included.

Data collection and analysis: A random-effects model was used to generate pooled adjusted risk ratios and 95% confidence intervals; subgroup and sensitivity analyses assessed the impact of monophasic-COC use and study-level characteristics.

Main results: There were 22 articles included in the analysis. The use of COCs containing cyproterone acetate, desogestrel, drospirenone, or gestodene was associated with a significantly increased risk of VTE compared with the use of levonorgestrel-containing COCs (pooled risk ratios 1.5-2.0). The analysis restricted to monophasic COC formulations with 30 μg of ethinyl estradiol yielded similar findings. After adjustment for study characteristics, the risk estimates were slightly attenuated.

Conclusions: Compared with the use of levonorgestrel-containing COCs, the use of COCs containing other progestogens could be associated with a small increase in risk for VTE.

Keywords: Combined oral contraceptives; Hormonal contraception; Meta-analysis; Risk; Systematic review; Venous thromboembolism.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / adverse effects*
  • Ethinyl Estradiol / administration & dosage
  • Female
  • Humans
  • Odds Ratio
  • Progestins / administration & dosage
  • Risk
  • Venous Thromboembolism / chemically induced*
  • Venous Thrombosis / chemically induced*


  • Contraceptives, Oral, Combined
  • Progestins
  • Ethinyl Estradiol