The neurokinin B pathway in the treatment of menopausal hot flushes

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.