Our understanding of VMS is heating up

It’s not all about estrogen

Declining estrogen isn’t the only cause of Vasomotor Symptoms (VMS), also known as hot flashes and night sweats—we now know that VMS results from altered activity of the kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the temperature control center of the hypothalamus.1,2

Inside the source of a hot flash

Inside the thermoregulatory center in the hypothalamus, specific neurons, known as KNDy neurons, contribute to the regulation of the body’s temperature.2

Inside the source of a hot flash

KNDy neurons are inhibited by estrogen and stimulated by the neuropeptide neurokinin B (NKB) in a delicate balance.3,4

Inside the source of a hot flash

Through the menopausal transition, declining estrogen disrupts the balance with NKB. Unopposed, NKB signaling increases KNDy neuronal activity—leading to hypertrophy of the KNDy neuron and altered activity on the thermoregulatory center.2,4,5

Inside the source of a hot flash

As a result, the thermoregulatory center triggers heat dissipation effectors that are experienced as hot flashes and night sweats, or VMS.2,5

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VMS IN HER WORDS - It throws everything off kilter; [there are] no rules on when or why they [hot flashes] happen, they just happen.

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References: 1. Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol 2007;196(2):97-106. 2. Padilla SL, Johnson CW, Barker FD, Patterson MA, Palmiter RD. A neural circuit underlying the generation of hot flushes. Cell Rep 2018;24(2):271-7. 3. Wakabayashi Y, Nakada T, Murata K, et al. Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat. J Neurosci 2010;30(8):3124-32. 4. Krajewski-Hall SJ, Blackmore EM, McMinn JR, Rance NE. Estradiol alters body temperature regulation in the female mouse. Temperature 2018;5(1):56-69. 5. Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, Blackmore EM, Rance NE. Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology 2019;160(4):803-16.
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