Current Evidence and Emerging Directions in Endometriosis Pharmacotherapy: A Systematic Review of Recent Advances

Background: Endometriosis affects 190 million women worldwide, so there is a need for accessible and more comprehensive knowledge regarding the pharmacotherapeutic options that can be offered to patients. This systematic review (2019-2025) synthesizes research results regarding the efficacy and safety of dienogest (DNG) and GnRH antagonists, while also summarizing research on new directions in endometriosis treatment. Methods: Following PRISMA 2020 guidelines, we searched Medline for clinical evidence on established standards and emerging therapies. A structured narrative synthesis was performed. Quality was assessed using Cochrane RoB 2 and ROBINS-I tools. Results: A total of 44 out of 926 records were analyzed. The review confirms the efficacy of DNG as a first-line treatment for endometriosis. Relugolix combination therapy appears to be a more effective and safer option than elagolix or relugolix monotherapy in reducing dysmenorrhea and pelvic pain. Research concerning immunotherapy for endometriosis (using tocilizumab, anakinra, bevacizumab, and anti-CD47 antibodies) is subject to a high risk of bias and very low GRADE certainty. Nevertheless, these findings may serve as a foundation for further studies, which are necessary to evaluate their efficacy and safety in the treatment of endometriosis. Conclusions: DNG is generally well-tolerated, but further studies are needed to unequivocally determine the impact of DNG on BMD loss and cancer risk. Research on GnRH antagonists indicates their increasing role in the future management of endometriosis. There are new perspectives in endometriosis pharmacotherapy-including immunotherapy; however, there is a fundamental need for their further development and evaluation.