The revised American Society for Reproductive Medicine (rASRM) classification of endometriosis scores 1–15 points as Stage I (minimal), 16–40 as Stage II (mild), and >40 as Stage III/IV. A woman with Stage IV deep infiltrating endometriosis with rectovaginal nodule is being considered for medical treatment to reduce pain before planned surgery. Dienogest (progestogen) exerts its anti-endometriotic effect via which specific mechanism?

• A Selective GnRH receptor antagonism causing complete oestrogen suppression
• B Inhibition of COX-2 in peritoneal macrophages reducing prostaglandin-mediated pain
• C Upregulation of progesterone receptor B isoform in ectopic lesions, reversing progesterone resistance
• D Antiproliferative and pro-apoptotic effects on ectopic endometrial cells via progesterone receptor, combined with local reduction of oestradiol synthesis by downregulating aromatase in ectopic lesions ✓

Explanation

Dienogest is a 19-norsteroid progestin with selective progesterone receptor agonist activity. In endometriosis, its anti-endometriotic mechanism is multi-pronged: it exerts direct antiproliferative and pro-apoptotic effects on ectopic endometrial stromal cells via progesterone receptors; it downregulates aromatase expression in ectopic endometrial tissue, reducing local oestrogen synthesis and eliminating the autocrine oestrogen–prostaglandin positive feedback loop that sustains lesion growth; and it reduces VEGF production, impairing neovascularisation of endometriotic implants. It does not cause systemic oestrogen deficiency (unlike GnRH analogues), so bone density impact is minimal.

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

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