Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) used for uterine fibroid treatment. In 2020, the EMA restricted its use due to rare but serious liver injury cases. UPA's mechanism for causing fibroid regression differs from GnRH agonists. Which best describes how UPA reduces fibroid size without complete oestrogen deprivation?

• A UPA inhibits progesterone signalling in fibroid cells, suppressing cell proliferation and inducing apoptosis, without causing pituitary downregulation or systemic oestrogen suppression ✓
• B UPA causes direct cytotoxicity in fibroid smooth muscle cells by alkylating DNA
• C UPA acts as a selective oestrogen receptor modulator in fibroid tissue, blocking oestrogen-driven proliferation
• D UPA causes amenorrhoea by thickening cervical mucus, which secondarily reduces fibroid blood supply

Explanation

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) that acts at progesterone receptors in fibroid tissue to exert antiproliferative and pro-apoptotic effects — fibroids are heavily dependent on progesterone signalling for growth. Unlike GnRH analogues that suppress pituitary LH/FSH causing systemic oestrogen deficiency (hot flushes, bone loss), UPA acts primarily at the tissue level: progesterone signalling is disrupted in fibroids and the endometrium (causing specific endometrial changes — 'PAEC': progesterone receptor modulator-associated endometrial changes), but systemic oestrogen levels remain near normal. The liver toxicity risk led to restricted use guidelines from EMA in 2020.

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

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Written and medically reviewed by the StethoPrep medical team.