Groter risico op veneuze trombose bij gebruik van orale contraceptiva van de 3e in vergelijking tot de 2e generatie; een meta-analyse

To quantitatively evaluate articles that compared the effects of second- and third-generation oral contraceptives for the risk of venous thrombosis using results obtained before October 1995.

Design

Meta-analysis.

Methods

A Medline search was conducted with the phrases ‘third-generation oral contraceptives’, ‘desogestrel’ and ‘gestodene’ and ‘thromboembolism’ and ‘venous thrombosis’, which was directed towards cohort and case-control studies published in the period October 1995-December 2000. Pooled adjusted odds ratios (OR) were calculated by means of a general-variance-based random effects method. Where possible, 2×2 tables were extracted, and combined using the Mantel-Haenszel method.

Results

The overall adjusted OR for third versus second-generation oral contraceptives was 1.7 (95 CI: 1.4-2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Amongst first time users, the OR for third- versus second-generation preparations was 3.1 (95 CI: 2.0-4.6; four studies). The OR was 2.5 (95 CI: 1.6-4.1; five studies) for short-term users compared with 2.0 (95 CI: 1.4-2.7; five studies) for longer-term users. The estimate was also dependent upon the source of funding; the OR was 1.3 (95 CI: 1.0-1.7) in studies funded by the pharmaceutical industry and 2.3 (95 CI: 1.7-3.2) in other studies. Differences in age and the certainty with which the diagnosis ‘venous thrombosis’ could be established, were not related to the results.

Conclusion

This meta-analysis supports the view that third-generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second-generation preparations. This increase was not explained by various potential biases.