Abstract
Changes in thermoregulation, notably the emergence of hot flashes, occur during the menopause transition in association with reproductive hormonal changes. Hot flashes constitute the most characteristic symptom of menopause (prevalence of 50-80%), and have a substantial negative effect on quality of life. Here, we review the endocrine changes associated with menopause and the thermoregulatory system and its sensitivity to female sex hormones. We then review current knowledge on the underlying neural mechanisms of hot flashes and how the reproductive and thermoregulatory systems interact in females. We consider the kisspeptin-neurokinin B-dynorphin (KNDy) neuron complex, which becomes hyperactive when estradiol levels decrease. KNDy neurons project from the arcuate nucleus to thermoregulatory areas within the hypothalamic preoptic area, where heat loss mechanisms are triggered, including cutaneous vasodilation and sweating - characteristics of the hot flash. We describe the physiology and measurement of hot flashes and discuss the mixed research findings about thresholds for sweating in symptomatic individuals. We consider the unique situation of hot flashes that arise during sleep, and discuss the relationships between the environment, exercise, and body mass index with hot flashes. We also discuss the unique situation of surgical menopause (with oophorectomy) and cancer therapy, conditions that are associated with frequent, severe, hot flashes. We then provide an overview of treatments of hot flashes, including hormone therapy and targeted neurokinin B-antagonists, recently developed to target the neural mechanism of hot flashes. Finally, we highlight gaps in knowledge about menopausal thermoregulation and hot flashes and suggest future directions for research.