Type of Combined Contraceptives, Factor V Leiden Mutation and Risk of Venous Thromboembolism

Objective: This article estimates the interaction between types of combined hormonal contraception (CHC) and factor V Leiden (FVL) mutation on the risk of venous thrombosis event (VTE).

Subjects And Methods: All premenopausal women with first incident VTE who were referred to our unit (Paris, France) between 2000 and 2009 were included in this case-only study. Differences in interactions by progestin type were assessed on a multiplicative scale, assuming the independence of genotype and prescription of type of CHC.

Results: Among 2,613 women with VTE, 15.9% had a FVL and 69% used CHC. The interaction between CHC use and presence of FVL on VTE risk was statistically significant (1.37, 1.06-1.77 95% confidence interval [CI]). This interaction appeared higher for drospirenone 1.99 (1.18-3.38 95% CI) ( = 98) or cyproterone acetate users 1.71 (1.20-2.45 95% CI) ( = 326), but not significant for 1st or 2nd or norgestimate CHC users. The results were similar when excluding women with a family history of VTE or with provoked VTE. In this sub-group of women, these interactions appeared higher for third generation, cyproterone acetate and drospirenone CHC users as compared with 1st or 2nd or norgestimate CHC users (odds ratio [OR], 1.68 [1.04-2.70; 95% CI], 2.91 [1.71-4.95 95% CI], 3.22 [1.54-6.73 95% CI], respectively).

Conclusion: Our results show that the interaction between FVL and CHC use differ by progestin type, which is higher in CHC containing third-generation progestin, drospirenone or cyproterone acetate, compared with second generation. Further studies are needed to assess the cost-effectiveness of biological thrombophilia screening (FVL) when such prescription of CHC is planned.