Role of hormonal therapies in endometriosis: balancing efficacy and safety

Introduction: Endometriosis is a chronic, estrogen-dependent inflammatory disorder requiring long-term management strategies that balance efficacy with systemic safety. Although hormonal therapies remain the cornerstone of treatment, the optimal degree of estrogen suppression needed to achieve durable symptom control while minimizing adverse effects remains controversial. Areas covered: This narrative review, based on a targeted PubMed/MEDLINE literature search and review of major guideline documents published up to January 2026, critically evaluates the efficacy, mechanisms of action, and safety profiles of combined oral contraceptives, progestins, GnRH agonists, and oral GnRH antagonists within an estrogen-threshold modulation framework. Expert opinion: Combined oral contraceptives and progestins remain preferred first-line therapies because they provide effective pain control with acceptable tolerability and preservation of bone health. GnRH agonists and oral GnRH antagonists offer more profound endocrine suppression and are particularly useful in women with moderate-to-severe pain or inadequate response to first-line treatment, although their use is limited by hypoestrogenic adverse effects. Increasing evidence suggests that maximal estrogen suppression is not universally necessary to achieve clinical benefit and may expose patients to unnecessary long-term toxicity. Future management will likely move toward individualized estrogen-threshold modulation integrated with multimodal pain management and biomarker-driven approaches.