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 g 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 30g 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.