Efficacy of Elagolix and Relugolix for the Treatment of Pelvic Pain in Patients With Endometriosis: A Systematic Review.

Endometriosis is a chronic gynecological condition commonly associated with pelvic pain, dysmenorrhea, dyspareunia, and infertility. Owing to the limitations and adverse effects of traditional hormonal therapies, this study aimed to evaluate the efficacy and safety of elagolix and relugolix for the management of endometriosis-related pain, in comparison with other therapeutic alternatives. A systematic search was conducted in PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane, SciELO, ScienceDirect, and Google Scholar, including randomized clinical trials (RCTs) published between 2014 and 2025. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, together with the GRADE and Jadad tools. Nine clinical trials met the inclusion criteria. The findings suggest that both relugolix and elagolix, whether administered as monotherapy or in combination with estrogens and progestins, effectively reduce endometriosis-associated pain, improve the quality of life, and decrease the need for opioid use. Reported adverse events were generally mild, with minimal loss of bone mineral density (BMD). Importantly, the strongest and most consistent evidence supports the use of relugolix in combination with add-back therapy, which appears to provide sustained efficacy and a more favorable long-term safety profile than monotherapy. Thus, relugolix with hormonal add-back therapy emerges as a safe and effective long-term treatment option for endometriosis-related symptoms, offering significant clinical benefits while mitigating hypoestrogenic side effects.