Thromb Haemost 2018; 118(05): 922-928
DOI: 10.1055/s-0038-1641152
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Stuttgart

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

Justine Hugon-Rodin
1  Unity 1018 in Centre de recherche en Épidémiologie et Santé des Populations (CESP), University Paris-Saclay and Paris-Sud, INSERM, Villejuif, France
2  Gynecology Endocrinology Unit, Hôpital Universitaire Paris-Centre, APHP, Paris, France
3  University Paris Descartes, Paris, France
,
Marie-Hélène Horellou
4  Hematology Biology Unit, Hôpital Universitaire Paris-centre, Paris, France
,
Jacqueline Conard
4  Hematology Biology Unit, Hôpital Universitaire Paris-centre, Paris, France
,
Anne Gompel
2  Gynecology Endocrinology Unit, Hôpital Universitaire Paris-Centre, APHP, Paris, France
3  University Paris Descartes, Paris, France
,
Geneviève Plu-Bureau
2  Gynecology Endocrinology Unit, Hôpital Universitaire Paris-Centre, APHP, Paris, France
3  University Paris Descartes, Paris, France
4  Hematology Biology Unit, Hôpital Universitaire Paris-centre, Paris, France
5  Equipe EPOPE, Inserm, Paris, France
› Author Affiliations
Funding This work was supported by funding from Agence Nationale de Sécurité du Médicament (ANSM, The French Drug Safety Agency) who played no role in the study.
Further Information

Publication History

04 October 2017

15 February 2018

Publication Date:
03 April 2018 (eFirst)

Abstract

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) (n = 98) or cyproterone acetate users 1.71 (1.20–2.45 95% CI) (n = 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.

Authors' Contributions

G.P.-B.: Conception, design, inclusion of patients, analysis, interpretation of data and revision of the manuscript. J.H.-R.: Analysis, interpretation of data and writing the manuscript. M.-H.H., J.C.: Collection of data, inclusion of patients, performing all biological analysis, interpretation of data and revision of the manuscript. A.G.: Interpretation of data and revision of the manuscript.