Ulipristal acetate (UPA) used for fibroid treatment works via which mechanism, and is associated with which histological endometrial change?

• A GnRH receptor agonism causing hypoestrogenism; associated with cystic glandular dilatation (PAEC)
• B Selective progesterone receptor modulation; associated with progesterone receptor modulator-associated endometrial changes (PAEC) ✓
• C Estrogen receptor downregulation; associated with endometrial atrophy
• D Aromatase inhibition in fibroid tissue; associated with endometrial hyperplasia

Explanation

Ulipristal acetate is a selective progesterone receptor modulator (SPRM) that acts on uterine fibroid tissue to inhibit cell proliferation and induce apoptosis, and on the hypothalamic-pituitary axis to suppress ovulation at higher doses. The characteristic endometrial finding is PAEC (progesterone receptor modulator-associated endometrial changes) — a benign, reversible pattern of cystically dilated glands with apoptotic/secretory changes and no nuclear atypia — which must be distinguished from endometrial hyperplasia. EMA/PRAC restrictions on UPA were introduced due to rare hepatotoxicity concerns.

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

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