GnRH antagonist (relugolix, elagolix) add-back therapy is now approved for symptomatic fibroids. Regarding elagolix (Oriahnn) for heavy menstrual bleeding due to fibroids, which pharmacodynamic mechanism distinguishes it from GnRH agonists?

• A Elagolix is a selective progesterone receptor modulator (SPRM) that directly acts on fibroid tissue
• B Elagolix achieves irreversible GnRH receptor downregulation superior to depot leuprolide
• C Elagolix requires subcutaneous injection and has a longer half-life than GnRH agonists
• D Elagolix is an oral non-peptide GnRH receptor antagonist that achieves immediate dose-dependent gonadotrophin suppression without an initial flare phenomenon ✓

Explanation

Elagolix (and relugolix) are oral, non-peptide, competitive GnRH receptor antagonists. Unlike GnRH agonists (leuprolide, buserelin) which initially cause a paradoxical flare of LH and FSH before downregulation (due to receptor agonism before desensitization), GnRH antagonists competitively block the receptor immediately with no flare. This allows dose-dependent, rapid, and reversible suppression of LH, FSH, estrogen, and progesterone. Elagolix 300 mg BD + add-back (estradiol 1 mg/norethindrone acetate 0.5 mg) is FDA-approved for heavy menstrual bleeding from fibroids. Relugolix (Myfembree) is a once-daily alternative. Both are oral, unlike most GnRH agonists which are injectables.

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

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