Third generation oral contraceptives and risk of venous thrombosis: meta-analysis

Objective To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis. Design Meta-analysis. Studies Cohort and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995. Main outcome measures Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two tay two tables were extracted and combined by the Mantel-Haenszel method. Results The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95%, confidence interval 1.4 to 2.0; seven studies). Similar-risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.'7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results. Conclusions This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with secund generation oral contraceptives. The increase cannot be explained by several potential biases.