The Therapeutic Role of Dienogest in Endometriosis-Associated Pain: From Basics to Clinics

The most common symptom of endometriosis is pain. The pathogenesis of endometriosis-associated pain remains unclear. In this review, we illustrate the pathogenesis of endometriosis-associated pain and the mechanisms of dienogest acts on endometriosis-associated pain, as well as therapeutic applications targeting these processes, by searching the literature in PubMed and Web of Science until May 2026. Abnormal distribution of nerve fibers, central sensitization, imbalance of inflammatory and immune environment, and hypoxic stress contribute to the generation of endometriosis-associated pain. Dienogest, as a fourth-generation selective progesterone receptor agonist, plays a key role in the treatment of endometriosis-associated pain by reducing serum estrogen levels, alleviating inflammatory responses, regulating nerve growth factor, modulating control central nervous system allergies, and influencing the biological processes of endometriotic stromal cells. Moreover, its long-term safety and tolerability are relatively satisfactory according to clinical studies, making it an effective therapeutic agent for endometriosis.