Menopause part I: Vasomotor symptoms (I)

Abstract

Menopause, an aged process due to loss of permanent ovarian function (mainly decreased production of estrogen) without another pathological or physiological cause becomes one of the most health issues in the world. Vasomotor symptoms (VMS) is a hallmark of menopause, occurring in up to 80 % of women experiencing and persisting for over seven years with significant negative impacts on physical, psychological, social, and overall wellbeing. Conventionally, menopause hormone therapy (MHT) is considered the most effective therapeutic opinion for many years based on the fact as “deficiency of estrogen”; however, the ratio of benefits and risk is highly debated and always in concern. Therefore, the non-MHT agent focusing the underlying pathophysiology of VMS, such as hypothalamus-pituitary-ovary axis is becoming attractive. Based on this concept, the hypothalamus neural construct containing Kisspeptin (Kp) neurons in median pre-optic area (POA) or Kp-neurokinin B (NKB)-dynorphin (DYN) neurons (KNDy neurons) in the infundibular nucleus is identified as the thermoregulatory circultry to involve the pathophysiology of normal reproduction and menopause-associated VMS. The neurokinin 3 receptor (NK3R) antagonists applied to VMS are an enthusiasm with a big success. Fezolinetant is one of the best breakthroughs. Recent three randomized clinical trials (RCTs), including SKYLIGHT 1,2, and 4 confirmed the safety and efficacy for treating moderate-to-severe VMS women. By contrast, another MONGLIGHT RCTs for East Asia population seemed to controversial therapeutic effect for VMS treatment, but there is no doubt that safety issue is also satisfied, contributing to the need of more RCTs to validate its efficacy in diverse population. The current review will summary the recent advance of this new landscape in the management of women with moderate-to-severe VMS and particularly focus on the fezolinetant product.