Ulipristal acetate (UPA) used for emergency contraception and uterine fibroids is a selective progesterone receptor modulator (SPRM). How does its mechanism differ from mifepristone despite both being antiprogestins?

• A UPA blocks estrogen receptors selectively in the uterus while mifepristone primarily blocks progesterone receptors in the corpus luteum
• B UPA is a partial antagonist with tissue-selective agonist properties at PR-B, inhibiting ovulation by delaying follicular rupture — effective up to 5 days post-coitus; mifepristone is a pure antagonist also blocking glucocorticoid receptors, with abortifacient activity at higher doses ✓
• C UPA inhibits 3β-HSD in the corpus luteum reducing progesterone synthesis; mifepristone competes at the progesterone receptor
• D UPA is a non-steroidal prostaglandin synthesis inhibitor that prevents implantation; mifepristone is a steroidal antiprogestin activating apoptosis in decidua

Explanation

Both mifepristone and ulipristal acetate (UPA) are steroidal compounds that bind progesterone receptors (PR), but they differ critically in their receptor pharmacology. Mifepristone is a competitive antagonist at both PR (predominantly PR-B) and glucocorticoid receptors (GR) with high affinity, effectively blocking progesterone-mediated decidualization and causing endometrial decidual breakdown — hence its abortifacient and medical abortion use at 200–600 mg. UPA is a selective progesterone receptor modulator (SPRM) that acts as a partial agonist/antagonist with tissue-selective activity: in the hypothalamus/pituitary, it inhibits LH surge and delays follicular rupture (effective up to 120 hours/5 days post-coitus, superior to levonorgestrel at that timepoint); in the endometrium, it inhibits cell proliferation and alters receptivity; in fibroids, it reduces leiomyoma volume. UPA has no significant anti-glucocorticoid activity at therapeutic doses for emergency contraception.

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

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