Ulipristal acetate (UPA) is a selective progesterone receptor modulator used as emergency contraception up to 120 hours post-coitus. Compared to levonorgestrel (LNG), its advantage at day 4–5 is mechanistically due to:

• A UPA can delay or inhibit follicular rupture even after the LH surge has begun (by inhibiting LH-induced follicular rupture), while LNG is only effective before the LH surge ✓
• B UPA inhibits CYP19 (aromatase) in the follicle, preventing estradiol surge and LH surge for a longer duration than LNG
• C UPA has anti-implantation effects via progesterone receptor modulation in the endometrium that are more potent than LNG's
• D UPA has a longer half-life than LNG, maintaining follicle-inhibiting plasma concentrations for 5 days

Explanation

Levonorgestrel (LNG) primarily inhibits or delays ovulation by suppressing the LH surge, but it is ineffective once the LH surge has begun. Ulipristal acetate, as a selective progesterone receptor modulator (SPRM), can delay or inhibit follicular rupture even when the LH surge is already underway, by inhibiting LH-receptor-mediated signalling pathways in the dominant follicle. This is the critical mechanistic difference explaining UPA's superior efficacy at days 4–5. Body weight above 70–75 kg reduces LNG's effectiveness, but UPA is less affected, though some reduction in efficacy occurs in obese women (>95 kg). Both mechanisms are primarily pre-fertilisation.

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

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Written and medically reviewed by the StethoPrep medical team.