Beyond Efficacy: Tolerability Profiles and Shared Decision-Making in Hormonal Management of Endometriosis-Associated Pain

Background: The management of endometriosis-associated pain has traditionally focused on analgesic efficacy. However, with high-level evidence demonstrating therapeutic equivalence among principal hormonal classes, the paradigm has shifted towards a patient-centred approach prioritising long-term tolerability and shared decision-making. Objectives: This review critically synthesizes the evidence for the three main hormonal therapies—gonadotropin-releasing hormone (GnRH) analogues, dienogest, and gestrinone—focusing on their distinct tolerability and safety profiles to inform this modern clinical framework. Methods: This narrative review followed the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. The literature search was performed in PubMed, Scopus, and Embase in June 2025. Results: Our comparative analysis, based on a structured literature search adhering to SANRA guidelines, shows that while all three classes are effective, they present distinct benefit-risk profiles: GnRH analogues offer potent pain relief but induce a hypoestrogenic state requiring add-back therapy to mitigate bone loss and vasomotor symptoms; dienogest preserves bone mineral density but is associated with challenging bleeding patterns and potential mood disturbances; and gestrinone provides robust efficacy with a favorable cardiovascular and skeletal safety profile, although its androgenic effects can significantly impact patient adherence. Conclusions: In the absence of a clear hierarchy of efficacy, the optimal therapeutic choice is not determined by potency, but by a collaborative process in which patient values and tolerance for specific adverse effects guide selection. This review provides a framework to facilitate this shared decision-making in clinical practice.