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.

KEYWORDS:

• Venous thromboembolism
• Combined hormonal contraception
• Oral contraceptives
• Transdermal contraceptive patch
• Vaginal contraceptive ring
• Cyproterone acetate
• Desogestrel
• Drospirenone
• Ethinylestradiol
• Levonorgestrel
• Gestodene
• Norelgestromin
• Norgestimate

Acknowledgements

Funding: This study benefited from an educational grant from the Fundación Española de Contracepción.

Declaration of interest: The authors FM, IR, EPC, and IL have participated in conferences, symposiums, and studies sponsored by various pharmaceutical companies. KL received economic support from Wyeth Lederle Spain to cover the expenses of the literature search. The authors alone are responsible for the study design, critical evaluation of the evidence, and elaboration of the manuscript.