Pathophysiology of Vasomotor Symptoms in Menopause

The panel begins by unpacking how hormonal fluctuations during menopause—especially estrogen decline—disrupt thermoregulatory mechanisms in the hypothalamus. This hormonal imbalance triggers instability in the body’s internal temperature control system, leading to sudden sensations of heat and perspiration. These reactions are tightly linked to neuroendocrine feedback loops that become hypersensitive during menopausal transition.

KNDy neurons (named for kisspeptin, neurokinin B, and dynorphin) play a central role in mediating these processes. Located in the hypothalamic arcuate nucleus, they help regulate gonadotropin-releasing hormone (GnRH) and temperature control. When estrogen levels drop, these neurons become overactive, producing neurochemical surges that manifest as hot flashes.

By targeting neurokinin receptors, particularly NK3 and NK1, researchers aim to rebalance this pathway. The segment underscores that understanding the interplay between estrogen signaling, KNDy neuron activity, and thermoregulation paves the way for more precise therapies that directly modulate these neural circuits.