Evaluation of the Efficacy and Safety of Gonadotropin-Releasing Hormone Antagonists in the Management of Endometriosis-Associated Pain: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Background Pain associated with endometriosis arises from the combined effects of inflammatory responses, tissue damage, and neural sensitization induced by ectopic endometrial lesions. Currently, oral non-peptide gonadotropin-releasing hormone (GnRH) antagonists are emerging as an effective therapeutic modality for this condition. Objective This study aims to conduct a comprehensive synthesis of evidence regarding the effectiveness of oral GnRH antagonists in alleviating pain symptoms associated with endometriosis. Search Strategy Search of four electronic databases, conducted in July 2025. Selection Criteria Only randomized controlled trials (RCTs) involving patients with endometriosis-related pain receiving GnRH antagonist therapy were included. Data Collection and Analysis Two independent reviewers conducted separate searches of the databases, assessed eligible articles for inclusion and employed the Cochrane Collaboration’s tool for assessing the risk of bias. Main Results Among the evaluated treatments,Meta-analysis found that linzagolix 200 mg（SMD=-0.51,95%-CI[-0.89,-0.12]）, relugolix 40 mg（SMD=-1.96,95%-CI[-2.43,-1.49]）, elagolix 400 mg（SMD=-0.73,95%-CI[-0.90,-0.55]）, and ASP1707 15 mg （SMD=-0.49,95%-CI[-0.79,-0.19]）demonstrated superior efficacy in reducing endometriosis-associated pain. In terms of safety profiles, elagolix 400 mg（RR=1.41,95%-CI[1.29,1.56]） and linzagolix 200 mg （RR=1.32,95%-CI[0.99,1.76]）were associated with the highest incidence of treatment-emergent adverse events (TEAEs). Conclusion Oral non-peptide GnRH antagonists have exhibited notable efficacy in alleviating endometriosis-associated pain, offering distinct advantages over conventional pharmacological treatments. However, their use is associated with an increased incidence of TEAEs, with a clear dose-dependent relationship observed.