Vasomotor Symptoms in Menopause: Modern Perspectives and Emerging Therapies

normal estrogenic conditions, a balance between these neuropeptides helps maintain a wide thermoneutral zone.However, as estrogen levels decline during menopause, the inhibitory control of dynorphin wanes, while excitatory NKB activity increases, leading to instability in core temperature regulation. 3his narrowed thermoneutral zone results in the body's heightened sensitivity to minor fluctuations in core body temperature, triggering exaggerated heat dissipation responses such as vasodilation (flushing) and perspiration.This process is frequently accompanied by arousal responses in the brain, which explains the associated sleep disturbances and affective symptoms. IntroductIonVasomotor symptoms (VMS) affect approximately 75-80% of women during the menopausal transition, with moderateto-severe symptoms in up to 40%. 1 These symptomscharacterized by sudden episodes of heat, sweating, palpitations, and anxiety-can lead to profound disruptions in daily functioning and quality of life.Contrary to older beliefs that VMS are short-lived, longitudinal studies indicate that symptoms may persist for a median of 7.4 years, and in some women even longer. 1 The severity and duration of symptoms vary based on individual factors such as age at menopause, body mass index (BMI), smoking status, ethnicity, and psychosocial stress.VMS are not only physically uncomfortable but are linked to sleep disturbance, mood disorders, and impaired occupational and interpersonal performance.Addressing VMS effectively is central to improving the overall health and well-being of menopausal women. PathoPhysIology o f Vasomotor symPtomsVasomotor symptoms arise from disruptions in hypothalamic thermoregulation (Fig. 1A). 2 At the core of this dysregulation are kisspeptin/neurokinin B/dynorphin (KNDy) neuronsnamed for their coexpression of kisspeptin, neurokinin B (NKB), and dynorphin-which reside in the infundibular nucleus (analogous to the arcuate nucleus in primates).Under 1,