Extended GnRH Agonist and NETA Add-Back: An Effective and Safe Option for Refractory Endometriosis/Adenomyosis Pain

Moamar Al‐Jefout, Shamsa Al Awar, Samer Yaghi, Omar Dabas
In: Biomedical and Pharmacology Journal · 2025 · vol. 18(3) , pp. 1938–1946 · doi:10.13005/bpj/3226 · W4414795056
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⚙ AI-generated summary by claude@2026-06, 2026-06-06 ⓘ

Prolonged GnRH agonist therapy with NETA add-back significantly reduced refractory endometriosis and adenomyosis pain and was well-tolerated in premenopausal women.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 ⓘ

This prospective, open-label, two-arm study enrolled 81 premenopausal Jordanian women with severe, refractory endometriosis-associated pain (all confirmed endometriosis; 46 also had adenomyosis) and treated them for 24 months with either long-acting triptorelin or goserelin plus daily norethisterone acetate (NETA) add-back. Across follow-up visits, mean pain scores for dysmenorrhea and deep dyspareunia decreased markedly (VAS 7.9→2.3 and 6.1→0.6, respectively; P<0.0001), and other symptoms such as dyschezia, dysuria, bloating, alternating bowel habits, and cold intolerance improved; mild osteopenia occurred in 2.4% with no major adverse events reported based on laboratory and imaging/DEXA follow-up. The study reports no control group and includes 29 participants lost to follow-up, which limits causal inference and generalizability. This paper is centrally about endometriosis and adenomyosis—specifically prolonged GnRH agonist therapy beyond 24 months with NETA add-back for refractory endometriosis/adenomyosis pain.

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Abstract

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.

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Outcome instruments

VAS-pain

Condition tags

endometriosisadenomyosisdysmenorrheadyspareunia

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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