Regarding GnRH antagonist add-back therapy in endometriosis management, which of the following represents the mechanism of action of relugolix-estradiol-norethindrone acetate (Myfembree) in preserving bone mineral density?
- A Low-dose oestrogen and progestogen add-back prevents the hypoestrogenic bone loss caused by GnRH antagonist-induced ovarian suppression ✓
- B Relugolix suppresses FSH only, preserving residual oestradiol from the corpus luteum
- C Norethindrone acetate independently stimulates osteoblasts independent of oestrogen levels
- D Relugolix selectively blocks endometrial GnRH receptors while sparing ovarian function
Explanation
Relugolix is an oral GnRH antagonist that rapidly and reversibly blocks GnRH receptors in the pituitary, suppressing LH and FSH → profound oestrogen suppression → addresses endometriosis symptoms. However, prolonged hypoestrogenism causes bone mineral density loss. The add-back combination (estradiol 1 mg + norethindrone acetate 0.5 mg) provides sufficient oestrogen to preserve BMD and reduce vasomotor symptoms without stimulating endometriotic lesions (Barbieri 'add-back threshold' concept). This strategy allows long-term treatment beyond the conventional 6-month GnRH agonist limit. The FDA approved relugolix combination tablet for endometriosis in 2022 based on the SPIRIT trials.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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