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Venous and pulmonary thromboembolism and combined hormonal contraceptives. Systematic review and meta-analysis

ABSTRACT Objective A systematic review of studies published between January 1995 and April 2010 aimed at determining the effect of combined hormonal contraceptives (CHCs), administered orally, transdermally or vaginally, on the risk of venous thromboembolism (VTE). Results Of the 625 potentially eligible references reviewed, 25 studies meeting the inclusion and exclusion criteria were entered in the meta-analysis. The pooled relative risks of VTE associated with the various CHCs, depending on their progestogen, were: gestodene vs. levonorgestrel 1.33 (95% confidence interval [CI]: 1.08–1.63); desogestrel vs. levonorgestrel 1.93 (95% CI: 1.31–2.83); and drospirenone vs. levonorgestrel 1.67 (95% CI: 1.10–2.55). The pooled adjusted odds ratio for norgestimate vs. levonorgestrel was 1.11 (95% CI: 0.84–1.46) and that for cyproterone acetate vs. levonorgestrel 1.65 (95% CI: 1.30–2.11). Conclusions The safest CHCs in terms of VTE are those containing levonorgestrel or norgestimate. The risk of VTE associated with desogestrel-, drospirenone- or cyproterone acetate-containing CHCs is greater than that associated with CHCs containing levonorgestrel. The increased risk of VTE found for CHCs with gestodene compared to CHCs with levonorgestrel seems smaller than in previous analyses. There were no differences in VTE risk between oral and transdermal CHCs containing norgestimate or norelgestromin, respectively.