Department of Obstetrics and Gynaecology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands.
Department of Obstetrics and Gynaecology, Amsterdam UMC, location Vrije Universteit MC, Amsterdam, The Netherlands.
Br J Clin Pharmacol. 2024 Feb;90(2):392-405. doi: 10.1111/bcp.15897. Epub 2023 Sep 27.
Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related 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-level characteristics limiting the predictability of treatment success in the real-world 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-term 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-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.
新型促性腺激素释放激素（GnRH）拮抗剂与激素补充疗法联合应用于治疗子宫肌瘤引起的月经过多，为女性提供了一种口服治疗选择。评估 GnRH 拮抗剂联合制剂（relugolix、elagolix 和 linzagolix）治疗与安慰剂相比治疗子宫肌瘤相关重度月经过多的注册试验已评估了该疗法的疗效。包括欧洲、英国和美国在内的多个机构已批准了该药物的上市许可。虽然注册试验报告称，该药物在减少重度月经过多和提高生活质量评分方面具有显著效果，但在广泛处方之前仍需谨慎。在本综述中，我们展示了试验数据的局限性，即由于研究人群受限，缺乏普遍性；疾病特征分布缺乏透明度，限制了在现实世界多样化人群中预测治疗成功的能力；并且缺乏与当前替代治疗方法的比较。重要的是， GnRH 拮抗剂联合制剂并未发现有临床意义的肌瘤体积缩小，并且需要进一步研究长期安全性数据，特别是关于适度但稳定的骨密度下降问题。子宫肌瘤相关症状严重影响了许多女性的生活质量，目前缺乏有效的治疗方法。然而，尽管对保守治疗的需求迫切，但在代表性人群中对新型药物（如口服 GnRH 拮抗剂联合制剂）进行充分的安全性、有效性和成本效益评估，并在引入主流临床实践之前与替代治疗方法进行比较，是至关重要的。
