The neurokinin B pathway in the treatment of menopausal hot flushes

Abstract

Hot flushes remain a debilitating aspect of menopause, disrupting daytime activities and sleep, and may last for years. Estrogen replacement is an effective treatment, but takes time to become maximally effective and is contraindicated in a significant proportion of women, most notably after breast cancer. Effective, non-hormonal therapies are therefore required. Recent years have seen substantial increases in understanding of the role of novel neuropeptides and tachykinins in hypothalamic function, particularly in the regulation of the reproductive axis through control of gonadotropin releasing hormone secretion, but with links to the control of vasomotor function. Neurokinin B, often co-expressed with kisspeptin in hypothalamic neurons, appears to be a key factor in the control of both systems. Several neurokinin B antagonists have been developed; data are emerging as to their effectiveness in the treatment of menopausal hot flushes. While data remain limited, these agents appear to have a remarkably fast onset of action, with the first 1 or 2 days of administration, and with a dramatic effect on both daytime flushes and night sleep disturbance. If safety and long-term function can be confirmed, these novel agents will be an important advance in therapy.

Chinese abstract

潮热仍然是更年期的一个令人衰弱的方面, 扰乱白天活动和睡眠, 可能持续数年。雌激素替代是一种有效的治疗方法, 但它需要时间才能发挥最大的作用, 并且在很大一部分女性中是禁忌的, 尤其是乳腺癌之后。因此需要有效的非激素疗法。近年来, 人们对新型神经肽和速激肽在下丘脑功能中所起作用的认识有了很大的提高, 尤其是通过控制促性腺激素释放激素的分泌来调节生殖轴, 但与控制血管舒缩功能有关。神经激肽B似乎是控制这两个系统的关键因素, 它常与下丘脑神经元中的kisspeptin共同表达。已经开发出几种神经激肽B拮抗剂；关于其治疗更年期潮热的有效性的数据正在浮现。虽然数据仍然有限, 但这些药物似乎在给药的前1天或2天就非常快的起效, 对白天潮红和夜间睡眠障碍都有显著作用。如果安全性和长期作用能够得到证实, 这些新型药物将是治疗的一个重要进展。

Keywords:

• Neurokinin B
• hot flushes
• vasomotor symptoms
• tachykinin

Conflict of interest

The authors report no conflict of interest.

Source of funding

Nil.