There were 26 studies included (nine cohort, 14 case-control and three nested case-control studies). The total sample size was not clear, but there were over two million women. Eight studies used an interview or questionnaire to assess contraceptive use (high risk of bias); only five objectively confirmed venous thrombosis (low risk). None of the cohort studies reported loss to follow-up. Generally none of the trials appeared to be at low risk for all potential causes of bias.
In 23 studies of progestogens, their use increased the risk of thrombosis compared to non-users, with relative risks of 3.2 for first-generation progestogens (95% CI 2.0 to 5.1), 2.8 for second generation (95% CI 2.0 to 4.1) and 3.8 for third generation (95% CI 2.7 to 5.4). The risk of thrombosis was similar for first and second generation users, but the risk was higher in third than in second generation users (RR 1.3, 95% CI 1.0 to 1.8). No evidence of inconsistency between direct and indirect evidence in the network was found.
Fourteen studies presented results that compared different types of oral contraceptive. All preparations at least doubled the risk of thrombosis compared to non-use. The risk was highest with 50LNG (50ug ethinyl estradiol with levonorgestrel, RR 5.2, 95% CI 3.4 to 7.9) and lowest for 20LNG (20ug ethinyl estradiol with levonorgestrel, RR 2.2, 95% CI 1.3 to 3.6) and 20GSD (20ug ethinyl estradiol with gestodene, RR 2.2, 95% CI 1.4 to 3.2). Higher doses of gestodene, desogestrel, and levonorgestrel were associated with increased risk. Full results of the analysis were presented.
Sensitivity analyses found that the risk of thrombosis in third generation users was lower in industry-funded studies and in cohort studies. Risk estimates were generally higher where venous thrombosis had been objectively confirmed.