Cucinella Laura, Tedeschi Sara, Memoli Stefano, Cassani Chiara, Martini Ellis, Nappi Rossella E
Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
Research Center for Reproductive Medicine, Gynecological Endocrinology and Menopause, IRCCS S. Matteo Foundation, Pavia, Italy.
Expert Opin Drug Metab Toxicol. 2025 Jan-Feb;21(2):105-113. doi: 10.1080/17425255.2024.2416046. Epub 2024 Oct 16.
Vasomotor symptoms (VMS) affect the majority of menopausal women, with possible negative impact on several domains of quality of life (QoL). Although menopausal hormone therapy (MHT) represents an effective treatment, the risk-benefit profile is not favorable for every woman. Non-hormonal options are limited in number and efficacy.
Fezolinetant is a novel oral non-hormonal drug recently approved for the treatment of moderate-severe VMS. It acts as an antagonist of neurokinin 3 receptor (NK3R), the main target of neurokinin B (a tachykinin over-expressed by kisspeptin/neurokinin B/dynorphin [KNDy] neurons after menopausal hypoestrogenism), involved in the modulation of the thermoregulatory hypothalamic center. Here, we report pharmacodynamics and pharmacokinetic properties of fezolinetant as well as its efficacy and safety data from available clinical trials.
Fezolinetant has shown efficacy in reducing the frequency and severity of VMS with a positive impact on sleep- and health-related QoL and acceptable safety and tolerability profile. Given the limited availability of effective non-hormonal options for VMS, fezolinetant could potentially represent a game-changer for care of menopausal women, especially when relative or absolute contraindications to MHT use are present. Further studies to gain more information about the safety profile and potential extra-VMS benefits or disadvantages are warranted in real-life clinical practice.
血管舒缩症状（VMS）影响着大多数绝经后女性，可能对生活质量（QoL）的多个方面产生负面影响。尽管绝经激素治疗（MHT）是一种有效的治疗方法，但风险效益比并非对每位女性都有利。非激素治疗选择的数量和疗效有限。
非索利坦是一种新型口服非激素药物，最近被批准用于治疗中重度VMS。它作为神经激肽3受体（NK3R）的拮抗剂发挥作用，神经激肽3受体是神经激肽B（一种在绝经后雌激素缺乏时由亲吻素/神经激肽B/强啡肽[KNDy]神经元过度表达的速激肽）的主要靶点，参与调节体温调节下丘脑中心。在此，我们报告非索利坦的药效学和药代动力学特性以及现有临床试验中的疗效和安全性数据。
非索利坦已显示出在降低VMS的频率和严重程度方面的疗效，对睡眠和健康相关的生活质量有积极影响，且安全性和耐受性良好。鉴于VMS有效非激素治疗选择有限，非索利坦可能会改变绝经后女性的护理模式，尤其是在存在MHT使用的相对或绝对禁忌证时。在现实临床实践中，有必要进行进一步研究以获取更多关于安全性概况以及潜在的VMS以外的益处或缺点的信息。
