{"paper_id":"1a59ab8d-058a-4c7e-9b13-301c904f0fa5","body_text":"ABSTRACT\nIntroduction\nIn ovarian steroid-dependent diseases such as uterine fibroids, endometriosis and adenomyosis, oral GnRH antagonists have emerged as new therapeutic alternatives. These oral GnRH antagonists offer key advantages, including oral administration, dose-dependent estrogen suppression and rapid reversibility.\nAreas covered\nThis review examines the pharmacological, clinical and therapeutic profiles of the latest non-peptide oral GnRH antagonists, through an analysis of clinical evidence and randomized clinical trials, to provide a comprehensive and up-to-date overview of their clinical applications and potential benefits.\nExpert opinion\nThe clinical trials examined demonstrated significant efficacy in reducing heavy menstrual bleeding in women with fibroids and pelvic pain in women with endometriosis, with more than 70% of patients achieving primary endpoints. The use of add-back therapy minimized bone mass density loss, ensuring long-term safety. Adverse events were dose-dependent but generally well tolerated. In our opinion, the strength of oral GnRH antagonists lies in their pharmacological properties. Oral administration increases convenience, allows adjustable dosing and ensures a dose-dependent effect. These drugs provide an immediate antagonistic effect without the flare-up phenomenon. Furthermore, they are expected to act on ectopic endometrial and smooth muscle cell receptors, potentially providing additional anti-proliferative effects. However, further research is needed: long term clinical trials must compare them with existing treatments.\nArticle highlights\nThree types of oral GnRH antagonist are available: elagolix, relugolix, linzagolix.\nThey have four peculiarities: oral administration, rapid reversibility of hormonal suppression, immediate suppression, dose-dependent effect.\nApproved for the treatment of heavy menstrual bleeding associated with uterine fibroids and endometriosis related pelvic pain in women of reproductive age.\nFavorable safety profile when used at low dosage or for short duration (up to 6 months).\nThe addition of an add back hormonal therapy ensures long-term administration while maintaining efficacy and safety.\nFurther comparative studies with other available drugs are mandatory to confirm their effectiveness.\nDeclaration of interest\nG. Grandi received honoraria for sponsored lectures and participation in advisory boards from Bayer AG, Teva/Theramex, Exeltis, Organon, Italfarmaco, Opocrin and Gedeon Richter. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.\nReviewer disclosures\nOne reviewer was involved in the clinical development of elagolix but is no longer employed by AbbVie (drug manufacturer) anymore. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.","source_license":"CC0","license_restricted":false}