GnRH Analogues for the Treatment of Endometriosis-Related Pain: A Narrative Review

Endometriosis is a chronic estrogen-dependent condition affecting women of reproductive age and commonly presents with dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. In a substantial proportion of patients, pain persists despite first-line hormonal treatment, making alternative pharmacologic strategies necessary. GnRH agonists and antagonists act primarily by suppressing ovarian estrogen production and thereby reduce an important hormonal driver of disease activity. Although both classes are effective for pain relief, they differ in onset of action, reversibility, tolerability, and suitability for prolonged use. This narrative review summarizes the current evidence on GnRH-based therapies for endometriosis-associated pain, with particular attention to biological rationale, clinical efficacy, safety, and the role of add-back therapy. Overall, both agonists and antagonists appear to provide clinically significant symptom improvement, especially in women who do not respond adequately to oral contraceptives or progestins. Their clinical use, however, is limited by hypoestrogenic adverse effects such as vasomotor symptoms and bone mineral density loss, which often require monitoring and adjunctive add-back therapy. Oral GnRH antagonists may offer practical advantages in selected patients through rapid action, the absence of a flare effect, and dose-adjustable hormonal suppression, although treatment choice must also consider long-term safety, cost, access, and individual patient characteristics. In summary, GnRH analogues remain useful second-line options, but treatment should be individualized according to symptom severity, previous treatment response, reproductive goals, tolerability, bone health, cost, and availability.