Contraceptive pills and venous thrombosis

Contraceptive pills are among the most popular contraception methods worldwide. A combined oral contraceptive pill contains two components, the estrogen and the progestagen compound. Despite its reliable contraception action, these pills may present side-effects including obstruction of leg and pulmonary vessels by clots (venous thrombosis). This side-effect is rare but the most frequently occurring serious adverse effect. Different combination pills show different vessel clotting obstruction tendencies (venous thrombosis risk). Evaluation of these different tendencies may play an important role in choosing the safest pill when starting pill use. COC containing higher estrogen doses (>30 μg) with levonorgestrel (a progestagen) or containing cyproterone acetate or drospirenone as progestagen are associated with higher VT risk than the oral contraceptive pill with 30 μg estrogen and levonorgestrel as progestagen. All combined monophasic oral contraceptive pills have the same effectiveness, that is preventing unwanted pregnancies. 

Authors' conclusions: 

All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed—that is, 30 μg ethinylestradiol with levonorgestrel.

Read the full abstract...

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available.


To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives.

Search strategy: 

Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions.

Selection criteria: 

We selected studies including healthy women taking COC with VT as outcome.

Data collection and analysis: 

The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies.

Main results: 

3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk.