In users of 2nd generation combined oral contraceptives (COCs), the incidence of venous thromboembolism (VTE) is estimated to be about 5 to 7 cases per 10 000 women-years of use. This translates into a mortality rate of 5 to 12 deaths per million women-years of use. In users of 3rd generation COCs the incidence of VTE is estimated to be about 6 to 12 cases per 10 000 women-years of use depending on the type of the progestogen used. The risk is estimated to be higher with the progestogens etonogestrel and norelgestromin, with 6 to 12 cases yearly per 10 000 women. The risk is also estimated to be higher with the progestogens gestodene, desogestrel, drospirenone, with 9 to 12 cases yearly per 10 000 women. For COCs containing chlormadinone, dienogest and nomegestrol, the available data are insufficient.
The incidence of VTE in women not using COCs and aged 15–44 years is 2 cases per 10 000 women-years. In pregnancy , the incidence is estimated as 10 to 20 cases per 10 000 pregnancies. It is expected that 20% of the women affected by a VTE will develop a disabling post-thrombotic syndrome. The most serious complication of VTE is pulmonary embolism which occurs in about 10% of the cases.
A Cochrane review included 25 observational studies (13 case-control, 9 cohort, and 3 nested case-control designs) with a total over 10 000 000 women years. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 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). A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk.