Oral Contraceptive Use and Venous Thromboembolism Risk

Oral contraceptives are among the most widely used forms of reversible birth control worldwide, combining an oestrogen component—most often ethinylestradiol or newer natural estrogens—and a progestogen to inhibit ovulation, alter cervical mucus and modify endometrial receptivity. Despite their efficacy and non-contraceptive benefits, combined preparations carry an elevated risk of venous thromboembolism (VTE), manifesting as deep vein thrombosis or pulmonary embolism. This risk varies with oestrogen dose, progestogen type and timing of use, with the highest relative incidence in the first year of initiation and attenuating with continued use. Underlying genetic predispositions, including inherited thrombophilias and polygenic risk profiles, further modulate individual susceptibility. Over the past decade, strategies to mitigate thrombotic risk have included reducing oestrogen doses, developing novel progestogens with more favourable haemostatic profiles and exploring baseline haemostatic screening. Emerging formulations based on natural oestrogens such as estetrol aim to retain contraceptive efficacy while exerting a lesser impact on coagulation factors. A balanced approach to prescribing requires integration of personal risk factors, genetic liability and patient preference to optimise safety and efficacy.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Oral Contraceptive Use and Venous Thromboembolism Risk publication trend

The graph below shows the total number of articles in oral contraceptive use and venous thromboembolism risk across all publications each year (not limited to Nature Index journals).

Technical terms

Venous thromboembolism (VTE): Formation of blood clots within the venous system, encompassing deep vein thrombosis and pulmonary embolism.

Progestogen: Hormonal agent in contraceptives that suppresses ovulation, thickens cervical mucus and alters endometrial receptivity.

Polygenic risk score: Numerical measure of inherited predisposition, calculated from the combined effect of multiple genetic variants.

Activated protein C resistance: Reduced anticoagulant response frequently stemming from specific genetic mutations, leading to heightened clotting tendency.

References

1. The risk of venous thromboembolism in oral contraceptive users: the role of genetic factors—a prospective cohort study of 240,000 women in the UK Biobank. American Journal of Obstetrics and Gynecology (2023).
2. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. The BMJ (2009).
3. Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk. Frontiers in Endocrinology (2021).