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Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid\u2010related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease\u2010level characteristics limiting the predictability of treatment success in the real\u2010world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long\u2010term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost\u2010effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.<\/jats:p>","DOI":"10.1111\/bcp.15897","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T04:51:25Z","timestamp":1693543885000},"page":"392-405","source":"Crossref","is-referenced-by-count":12,"title":["Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-6270","authenticated-orcid":false,"given":"Maria E.","family":"de Lange","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology Amsterdam UMC, location AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Semmler","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Amsterdam UMC, location Vrije Universteit MC  Amsterdam The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Justin","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Birmingham Women's and Children's Hospital  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben Willem J.","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Monash University Monash Medical Centre  Clayton Victoria Australia"},{"name":"Department of Obstetrics and Gynaecology, Aberdeen Centre for Women's Health Research University of Aberdeen  Aberdeen UK"},{"name":"Department of Obstetrics and Gynaecology University of Aberdeen  Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre M.","family":"Bet","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A. 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