GnRH antagonist (relugolix) for uterine fibroids is combined with low-dose estradiol and norethindrone acetate add-back therapy. The purpose of add-back therapy is:

• A To enhance fibroid shrinkage by maintaining partial estrogen stimulation
• B To prevent regrowth of fibroids after stopping relugolix
• C To prevent hypoestrogenic side effects (vasomotor symptoms, bone loss) while maintaining fibroid size reduction ✓
• D To reduce the risk of endometrial hyperplasia caused by relugolix

Explanation

GnRH antagonist therapy (relugolix, elagolix) induces profound hypoestrogenism to shrink fibroids, but this also causes vasomotor symptoms and accelerated bone mineral density loss. Add-back therapy with low-dose estradiol (1 mg) plus norethindrone acetate (0.5 mg) maintains estrogen levels sufficient to prevent menopausal side effects and bone loss without rescuing fibroid growth — the 'therapeutic window' concept. This allows long-term use beyond 6 months. It does not enhance fibroid reduction or prevent post-treatment regrowth.

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

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Written and medically reviewed by the StethoPrep medical team.