A 32-year-old woman taking a combined oral contraceptive pill containing ethinyl estradiol and desogestrel presents with a deep vein thrombosis. Compared with a levonorgestrel-containing pill, her preparation carries a higher thrombotic risk because:

• A Desogestrel has greater androgenic activity, increasing factor VII levels
• B Desogestrel binds SHBG more avidly, displacing bound estrogen
• C Desogestrel induces hepatic CYP3A4, raising ethinyl estradiol levels
• D Desogestrel has less androgenic activity, allowing unopposed estrogen-driven procoagulant protein synthesis ✓

Explanation

Third-generation progestins such as desogestrel and gestodene are less androgenic than levonorgestrel. Androgenic progestins partially counter the hepatic procoagulant effect of estrogen, so low-androgenicity preparations leave estrogen-driven increases in factors II, VII, IX, X and fibrinogen relatively unopposed, roughly doubling venous thromboembolism risk versus levonorgestrel pills. Option C is wrong because desogestrel does not induce CYP3A4; enzyme inducers reduce rather than raise estrogen levels.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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