Oral Contraceptive Use and Risk of Venous Thromboembolism in Carriers of Inherited Thrombophilias

Abstract

Introduction: Combined oral contraceptives (COCs) increase venous thromboembolism (VTE) risk, especially in thrombophilia carriers. Quantifying absolute risk guides contraceptive counseling.
Methods: Literature review of cohort and nested case-control studies. Inclusion: women with Factor V Leiden, prothrombin mutation, or protein S/C deficiency using COCs. Primary outcome: incident VTE per 10,000 woman-years.
Results: Twelve studies (n=25,000 carriers) were included. Baseline VTE risk in non-users was 5/10,000; in COC users, it rose to 40/10,000 for Factor V Leiden heterozygotes, 60/10,000 for prothrombin mutation, and 100/10,000 for compound heterozygotes. Progestin-only pills had no increased risk. Fourth-generation COCs (with drospirenone) showed higher risk than levonorgestrel.
Discussion: Absolute VTE risk in thrombophilia carriers on COCs remains below pregnancy-associated risk (200–300/10,000). However, risks are substantial and should prompt discussion of non-hormonal alternatives.
Conclusions: COC use in thrombophilia carriers increases VTE risk in a genotype-dependent manner. Progestin-only methods are safe. Screening before COC prescription is not cost-effective for all, but family history guides testing.