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www.thelancet.com Vol 389 May 6, 2017 1775 Within the next 25 years, an estimated 1 billion women worldwide will be older than 50 years, and therefore likely to be nearing menopause or postmenopausal. Hot flushes (vasomotor symptoms) are experienced by approximately 73% of postmenopausal women, and the associated sleep disturbances, fatigue, and decreased cognitive function lead to a reduction in their quality of life and an increased use of medical resources. A hypothalamic mechanism is well established in the understanding of hot flushes, but the pathways involved have been unclear, thus reducing therapeutic options. Novel hypothalamic neuropeptide-signalling pathways have shed light on the central regulation of both reproductive and thermoregulatory systems and the links between them, and might now lead to specific therapies. The menopause results in oestrogen deficiency, with loss of feedback regulation of hypothalamic gonadotropinreleasing hormone (GnRH). The kisspeptin–neurokinin B (NKB)–dynorphin (KNDy) signalling system in the hypothalamus is the proximate and obligate stimulus of GnRH secretion, and is hypertrophied after the menopause. Hypothalamic NKB neurons also project to the medial preoptic area, the hypothalamic site of thermoregulatory neuronal pathways, and evidence exists that these NKB neurons are a key link between the endocrine changes of the menopause and vasomotor symptoms. Flushing, like thermoregulation, is controlled centrally but effected peripherally, and blood flow to the skin is also increased in postmenopausal women with severe flushing. NKB neurons might also facilitate cutaneous vasodilatation and contribute to oestrogenic modulation of body temperature. In The Lancet, Julia Prague and colleagues report the findings from their phase 2, randomised, doubleblind, placebo-controlled trial investigating the oral neurokinin 3 receptor (NK3R) antagonist MLE4901 as a new therapy for menopausal hot flushes. In 28 healthy women aged 40–62 years, oral administration of a New pathways in the treatment for menopausal hot flushes Coramed to study a point-of-care device that assesses thrombogenicity; and has patents on platelet function testing (patent numbers: 8058023, 8070678, 9188597, 9110062, 8440420). UST declares no competing interests.