Venous thromboembolism risk differs between generations of progestins used in combined oral contraceptives. Which statement is correct?

• A Third-generation progestins such as desogestrel carry lower VTE risk than levonorgestrel
• B Third-generation progestins such as gestodene carry higher VTE risk than levonorgestrel ✓
• C Levonorgestrel-containing pills carry higher VTE risk than desogestrel-containing pills
• D All progestins confer identical VTE risk regardless of generation

Explanation

Third-generation progestins, namely desogestrel and gestodene, are associated with roughly a two-fold higher venous thromboembolism risk compared with the second-generation progestin levonorgestrel, likely related to greater resistance to activated protein B. This finding killed their initial marketing claim of improved safety. Drospirenone, a newer analogue, shows a similar elevation in risk. Estrogen dose remains the dominant driver of overall thrombotic risk.

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

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Written and medically reviewed by the StethoPrep medical team.