Vasomotor symptoms: modulation of the neurokinin 3 receptors

Abstract

Vasomotor symptoms (VMS) are highly prevalent, up to 80%, among peri- and postmenopausal women. Their frequency and intensity may impose a considerable effect on the quality of life (QoL) of many subjects. There is strong evidence in favor of hormone therapy as the most appropriate option to control VMS. Research on the pathophysiology of VMS has shown that the mechanism consists of an increased sensitivity of the thermo-regulatory centre at the hypothalamus. The system is regulated by estrogens, and new data have shown the implication of the group of kisspeptin-neurokinin-dynorphin (KNDY) neurons. The decline in estrogens liberates the release of neurokinin-3 that, through increased interaction with NK3 receptors (NK3R) at the median preoptic nucleus, resets the thermal threshold to favor the heat dissipation mechanism. Research in the latter years has come to synthesize specific antagonists of the NK3R receptors, which have confirmed efficacy in experimental models and early stages of clinical research, and finally have arrived at the level of clinical trials. The interest of current research mainly concentrates on the efficacy on VMS and on safety. The good balance at this level has opened new areas that have experienced indirect improvement. Among them, QoL, severely affected when VMS are frequent and severe, something that affects around 25% of the women. Several QoL dimensions, like the quality of sleep, sexual function, or performance in daily living are being investigated. Interest has also arisen in the use by patients who cannot, or do not accept hormone therapy. Survivors of endocrine related tumors, like breast cancer, are one of the several groups potentially affected.