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

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.