Potency of oral gonadotropin-releasing hormone antagonist as endometriosis-associated pain novel treatments: An updated meta-analysis of randomized controlled trials

Tjahyadi D, Dian Tjahyadi, Riyadi AS, Anthony Sudono Riyadi, Nugrahani AD, Annisa Dewi Nugrahani, Ritonga MA, Mulyanusa Amarullah Ritonga, Anita Rachmawati, Rachmawati A, Tita Husnitawati Madjid, Madjid TH
International journal of reproductive biomedicine · 2025 · vol. 23(9) , pp. 671–688 · doi:10.18502/ijrm.v23i9.20156 · PMID:41306462 · PMC12603575 · W4415765230
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Oral GnRH antagonists significantly reduce endometriosis pain but are associated with increased hot flushes, elevated LDL, and decreased bone mineral density.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

This updated meta-analysis assessed the potency of an oral gonadotropin-releasing hormone antagonist for endometriosis-associated pain by pooling evidence from randomized controlled trials and summarizing effects across studies. The authors’ key finding is the pooled estimate of analgesic efficacy for this drug class in the included RCTs. A major caveat in meta-analyses is that the reliability of pooled results depends on the quality, dosing/regimen consistency, and outcome reporting across the included trials, which the paper’s synthesis is constrained by. This paper is centrally about endometriosis — it specifically meta-analyzes randomized trials of an oral gonadotropin-releasing hormone antagonist for endometriosis-associated pain.

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Abstract

BACKGROUND: Elagolix, Linzagolix, and Relugolix, as oral gonadotropin-releasing hormone antagonists, have emerged as promising treatments for endometriosis-associated pain. OBJECTIVE: To evaluate pain intensity reduction as the primary outcome and assess side effects and quality of life as secondary outcomes through an updated meta-analysis. MATERIALS AND METHODS: A systematic search was conducted in Cochrane, Scopus, and PubMed/Medline. Study quality was assessed using the Cochrane risk of bias in non-randomized studies of interventions tool. The pooled standard mean difference and p-value were calculated using a random-effects model (DerSimonian-Laird method), and the inconsistency index was applied to evaluate heterogeneity. RESULTS: 7 randomized controlled trials were included. Gonadotropin-releasing hormone antagonists significantly reduced dysmenorrhea, dyspareunia, and non-menstrual chronic pelvic pain when measured with the verbal and numeric rating scales, but not with the modified Biberoglu and Behrman score. Secondary outcomes showed significant improvements in health status (endometriosis health profile and patient global impression of change). However, treatment was associated with increased hot flushes (3.61-fold higher), an 8.96% increase in low-density lipoprotein after 6 months, and a rise in high-density lipoprotein compared with placebo. Bone mineral density in the spine was significantly lower in the treatment group (p < 0.001). CONCLUSION: This meta-analysis provides updated evidence on Elagolix, Linzagolix, and Relugolix, confirming their effectiveness in managing endometriosis-associated pain, while highlighting important considerations regarding metabolic and bone health.
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Section

D. Tjahyadi: Conceptualization, study design, methodology, data curation, and manuscript drafting. A. Sudono Riyadi: Methodology, statistical analysis, resources, and critical revision of the manuscript. A. Dewi Nugrahani: Data extraction, project administration, statistical analysis, and manuscript editing. M. Amarullah Ritonga: Validation, data interpretation, and supervision. A. Rachmawati: Validation, data interpretation, and supervision. T. Husnitawati Madjid: Validation, data interpretation, and supervision.

Coi Statement

The authors declare that there is no conflict of interest.

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Outcome instruments

EHP-30 NRS-pain Biberoglu-Behrman

Condition tags

endometriosischronic_pelvic_paindysmenorrheadyspareunia

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.

References (38)

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