Dienogest (2 mg daily) is a selective progestogen used in endometriosis. Its mechanism differs from combined OCP progestins because it acts via which specific pathway most relevant to endometriosis suppression?

• A Strong pituitary gonadotrophin suppression preventing estrogen synthesis
• B Aromatase inhibition in endometriotic tissue reducing local estrogen production
• C GnRH receptor partial agonism at pituitary level causing selective LH suppression
• D Direct progestogenic activity on endometriotic stromal cells plus local anti-inflammatory and anti-angiogenic effects, with minimal systemic androgen or glucocorticoid activity ✓

Explanation

Dienogest is a 19-nortestosterone derivative progestin with high receptor selectivity (progesterone receptor with negligible androgen, glucocorticoid, or mineralocorticoid activity). Its mechanisms relevant to endometriosis include: direct decidualisation and apoptosis induction in ectopic endometrial cells, suppression of local inflammatory mediators (IL-8, RANTES, MCP-1), anti-angiogenic effects on neovascularization within lesions, and moderate hypoestrogenic effect (reduces E2 by ~50% but not to post-menopausal levels). Unlike GnRH agonists, it does not cause profound hypoestrogenism or bone loss, making it suitable for long-term use. Aromatase inhibition is not a dienogest mechanism.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

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