Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis

Controversy exists regarding whether oral contraceptives (OCs) containing d esogestrel and gestodene are associated with an increased risk of venous th romboembolism (VTE) versus OCs containing levonorgestrel. We were intereste d in synthesizing the available data, exploring explanations for mixed resu lts, and characterizing the degree of uncontrolled confounding that could h ave produced a spurious association. We performed a meta-analysis and formal sensitivity analysis of studies tha t examined the relative risk of VTE for desogestrel and gestodene versus le vonorgestrel. Twelve studies, all observational, were included. The summary relative risk (95% CI) was 1.7 1.3-2.1; heterogeneity p = 0.09). If real, the incremental risk of VTE would be about 11 per 100,000 women per year. A n association was present when accounting for duration of use and when rest ricted to the first year of use in new users. However, in the sensitivity a nalysis, the association abated in many, but not all, scenarios in which an unmeasured confounding factor increased the risk of VTE three to fivefold and in nearly all examined scenarios in which the factor increased the risk 10-fold. The summary relative risk of 1.7 does not appear to be caused by depletion of susceptibles, but is sensitive to a modest degree of unmeasured confound ing. Whether such confounding occurred is unknown. However, given this sens itivity, this issue probably cannot be settled unequivocally with observati onal data. In the absence of a definitive answer, this apparent increased r isk, together with its uncertainty and small magnitude and its important co nsequences, should be considered when selecting an OC for a given woman. (C ) 2001 Elsevier Science Inc. All rights reserved.