Neurokinin 3 Receptor Antagonism: A Novel Treatment for Menopausal Hot Flushes

Menopause is associated with significant symptomatic burden, with approximately two-thirds of postmenopausal women suffering from vasomotor symptoms, hot flushes, and night sweats. The mainstay of treatment for hot flushes continues to be hormone replacement therapy. However, as hormone replacement therapy is contraindicated in some cases, alternative, efficacious treatment options are also required. Hot flushes are thought to arise as a result of significant changes in the neuroendocrine circuitry underpinning the reproductive axis during menopause. This includes reduced circulating ovarian oestrogens, hypersecretion of gonadotropins, and increased expression of kisspeptin and neurokinin B (NKB) within the infundibular nucleus of the hypothalamus. In recent years, NKB, predominantly acting via the neurokinin 3 receptor (NK3R), has emerged as an important player in the development of menopausal hot flushes. Antagonism of NK3R has garnered much interest as a novel therapeutic target to help ameliorate hot flush symptoms. Improvements in hot flush frequency, severity, and quality of life have been demonstrated in a number of clinical trials using novel NK3R antagonists in postmenopausal women. Within this review, we will explore the growing body of evidence supporting antagonism of NK3R as a potentially promising treatment for menopausal hot flushes.