eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2025-09-30 18 3 1938 1946 10.13005/bpj/3226 67534 article Moamar AL-Jefout 1 Shamsa Al Awar 1 Samer Yaghi 2 Omar Dabas 2 Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE Department of Obstetrics and Gynecology, Faculty of Medicine, Mutah University, Mutah, Jordan This prospective, open-label, two-arm clinical study evaluated the efficacy and safety of prolonged gonadotropin-releasing hormone agonist (GnRH-a) therapy exceeding 24 months, combined with norethisterone acetate (NETA) add-back, in women experiencing endometriosis-associated pain refractory to standard treatments. Eighty-one premenopausal women with confirmed endometriosis and/or adenomyosis received either Triptorelin SR 11.25 mg or Goserelin acetate 10.8 mg every three months, together with daily NETA 5 mg for 24 months. Significant reductions in dysmenorrhea and deep dyspareunia were observed, with mean visual analogue scale scores decreasing from 7.9 to 2.3 and 6.1 to 0.6, respectively (P < 0.0001), along with improvements in dyschezia, dysuria, bloating, alternating bowel habits, and cold intolerance. Mild osteopenia occurred in only 2.4% of participants, and no major adverse events were reported, confirming safety through laboratory and imaging follow-up. These findings suggest that long-term GnRH-a therapy with NETA add-back is highly effective and well-tolerated in women with severe, treatment-resistant endometriosis-related pain, and may serve as a viable second-line medical treatment when surgery is not feasible. https://biomedpharmajournal.org/vol18no3/extended-gnrh-agonist-and-neta-add-back-an-effective-and-safe-option-for-refractory-endometriosis-adenomyosis-pain/ Add-Back Therapy Adenomyosis Chronic Pelvic Pain Endometriosis GnRH Agonist Long-Term Safety