A 26-year-old woman using combined OCP (ethinyl estradiol + levonorgestrel) develops deep vein thrombosis. The hormonal mechanism underlying increased VTE risk with estrogen-containing contraceptives is:
- A Progestins in the OCP directly activate platelet ADP receptors, enhancing platelet aggregation
- B Estrogen increases hepatic synthesis of clotting factors II, VII, IX, X and decreases protein C and S, shifting the coagulation balance toward thrombosis ✓
- C Estrogen reduces antithrombin III synthesis, eliminating the main inhibitor of thrombin and Factor Xa
- D The combined pill induces Factor V Leiden mutation in genetically susceptible women
Explanation
Estrogen induces hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) and simultaneously decreases natural anticoagulants (protein C, protein S, antithrombin III to a lesser extent). This shifts the haemostatic balance toward hypercoagulability and increases VTE risk approximately 3–5-fold over baseline. Third-generation progestins (desogestrel, gestodene) further increase VTE risk compared to second-generation progestins (levonorgestrel, norgestrel) because they also reduce free protein S. Women with underlying thrombophilia (Factor V Leiden, prothrombin G20210A) have a disproportionately higher risk.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.