Relugolix–estradiol–norethisterone for treating symptoms of endometriosis

NICE has stated that (1):

• relugolix–estradiol–norethisterone (relugolix combination therapy [CT]) can be used, within its marketing authorisation, as an option for treating symptoms of endometriosis in adults of reproductive age who have had medical or surgical treatment for endometriosis

The NICE committee stated that "...After pain relief and hormonal treatment, usual treatment options for endometriosis are gonadotropin-releasing hormone (GnRH) agonists and surgery. There is no cure for endometriosis, and there is an unmet need for long-term and non-invasive (non-surgical and not injected) treatments for its symptoms...Clinical trial evidence shows that relugolix CT reduces pain compared with placebo. Relugolix CT has not been directly compared in a clinical trial with usual treatment. Indirect comparisons suggest that it is likely to reduce pelvic pain almost as well as GnRH agonists. But it is unclear how well relugolix CT works compared with surgery.."

A review has stated that "the gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix decreases estradiol and progesterone levels, while the addition of estradiol/norethisterone acetate mitigates hypoestrogenic effects including bone mineral density (BMD) loss and vasomotor symptoms" (2):

• in clinical trials, relugolix CT improved period pain and pain between periods in women with moderate to severe pain associated with endometriosis
• relugolix CT improved other endometriosis related symptoms (overall pelvic pain and pain during sex), reduced the need for pain medications and improved health-related quality of life
• relugolix CT was generally well tolerated and caused minimal bone loss, which is known to occur with some hormone therapies
• relugolix CT is a once-daily oral pill

Reference:

1. NICE (April 2025). Relugolix–estradiol–norethisterone for treating symptoms of endometriosis
2. Blair HA. Relugolix/Estradiol/Norethisterone Acetate: A Review in Endometriosis-Associated Pain. Drugs. 2024 Apr;84(4):449-457.