Sassarini Jenifer, Anderson Richard A
School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK.
Centre for Reproductive Health, Institute for Repair and Regeneration, University of Edinburgh, Edinburgh, UK.
Expert Opin Investig Drugs. 2024 Jan;33(1):19-26. doi: 10.1080/13543784.2024.2305122. Epub 2024 Feb 12.
Menopausal vasomotor symptoms (VMS) are experienced by most women and are often debilitating and can last for years. While hormone replacement therapy is effective, it carries risks that have impacted its wider use, and it can be contraindicated. There is a large unmet need for a safe, effective non-hormonal therapy.
The importance of the neurokinin (NK) system in the hypothalamic regulation of the vasomotor center has become clear. NK antagonists, previously developed for other indications, have therefore been investigated for the treatment of VMS. Elinzanetant is a potent antagonist at both NK1 (endogenous ligand Substance P) and NK3 (neurokinin B) receptors, whereas other related drugs in development are selective NK3 antagonists. Elinzanetant has been investigated in 2 Phase II trials for menopausal VMS, demonstrating rapid onset and dose-dependant efficacy for the relief of VMS and improvement in quality of life for up to 12 weeks. Phase III trials are underway in women both with physiological menopause and after treatment for breast cancer.
Elinzanetant is a very promising non-hormonal approach to a highly prevalent symptom constellation, with rapid onset and high efficacy. Wider indications are being explored in current Phase III trials.
大多数女性都会经历绝经后血管舒缩症状（VMS），这些症状往往使人虚弱，且可能持续数年。虽然激素替代疗法有效，但它存在一些风险，影响了其更广泛的应用，并且可能存在禁忌证。对于安全、有效的非激素疗法存在巨大的未满足需求。
神经激肽（NK）系统在下丘脑对血管舒缩中枢的调节中的重要性已变得清晰。因此，先前为其他适应证开发的NK拮抗剂已被研究用于治疗VMS。艾林扎坦是NK1（内源性配体P物质）和NK3（神经激肽B）受体的强效拮抗剂，而其他正在研发的相关药物是选择性NK3拮抗剂。艾林扎坦已在两项针对绝经后VMS的II期试验中进行了研究，显示出起效迅速且具有剂量依赖性疗效，可缓解VMS并改善长达12周的生活质量。III期试验正在生理绝经女性和乳腺癌治疗后的女性中进行。
艾林扎坦是一种非常有前景的非激素方法，用于治疗高度普遍的症状群，起效迅速且疗效显著。目前的III期试验正在探索更广泛的适应证。
