Ulipristal acetate is used for emergency contraception and also as treatment for uterine fibroids. Its mechanism of action on the uterine endometrium involves which specific receptor interaction?

• A Full antagonism at endometrial progesterone receptors, causing endometrial shedding similar to mifepristone
• B Competitive estrogen receptor antagonism in the uterus, creating a hypoestrogenic state unfavorable for implantation
• C Selective progesterone receptor modulator (SPRM) activity — endometrium-specific partial agonist/antagonist at progesterone receptors, causing 'PAEC' (progesterone receptor modulator-associated endometrial changes) that are distinct from atrophy or hyperplasia ✓
• D Direct oxytocin receptor blockade preventing implantation by preventing endometrial decidualization

Explanation

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) that has tissue-specific mixed agonist/antagonist activities at progesterone receptors. In the endometrium, UPA delays follicular rupture (delaying ovulation) and alters endometrial receptivity. Chronic UPA use (for fibroids) causes a unique endometrial histological pattern called PAEC (progesterone receptor modulator-associated endometrial changes) — characterized by cystically dilated glands with a secretory pattern and inactive stroma — which is distinct from the endometrial atrophy seen with progestins, the hyperplasia from estrogens, or the decidualization from full progesterone agonists. PAEC is benign and reversible but requires endometrial assessment during long-term fibroid treatment. UPA also inhibits fibroid cell proliferation via anti-proliferative effects on fibroid PR-A/PR-B.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.