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The mechanism of VMS

Oestrogen decline contributes to altered neuronal activity in the hypothalamus1,2

Upon oestrogen decline, vasomotor symptoms (VMS), also known as hot flushes and night sweats, result from altered activity of the kisspeptin/neurokinin B/dynorphin (KNDy) neurons present in the hypothalamus acting on the temperature control centre of the hypothalamus.2,3

Inside the source of a hot flush

Oestrogen and neurokinin B (NKB) modulate KNDy neurons in a delicate balance, contributing to body temperature regulation. KNDy neurons are stimulated by NKB and inhibited by oestrogen.2,4,5

KNDy neuron shows neurokinin B and oestrogen molecules.

Inside the source of a hot flush

Through the menopausal transition, oestrogen declines, disrupting the balance with NKB.2,4,6

A KNDy neuron showing an oestrogen molecule near an oestrogen alpha receptor and a neurokinin B near a neurokinin 3 receptor.

Inside the source of a hot flush

Unopposed, NKB signalling causes heightened KNDy neuronal activity, which leads to hypertrophy of KNDy neurons and altered activity on the temperature control centre.2,4,6

A KNDy neuron showing all neurokinin B receptors glowing, and only one oestrogen receptor glowing.

Inside the source of a hot flush

As a result, the thermoregulatory centre triggers heat dissipation effectors that cascade into VMS, also referred to as hot flushes and night sweats.2,4,6

Brain with a cross section of the hypothalamus highlighted.

Watch how it works

Middle-aged menopausal woman on the beach looking happy

Not actual patients

VMS in her words

“I never know when they’re coming. I just have to suffer through them when they happen.”

Download the mechanism of VMS card

Uncover the burden of VMS
Learn about the mechanism of vasomotor symptoms (VMS) and see how VMS result from altered activity in the hypothalamus.

References:

  1. Monteleone P, Mascagni G, Giannini A, et al. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol 2018;14(4):199-215.
  2. Padilla SL, Johnson CW, Barker FD, et al. A neural circuit underlying the generation of hot flushes. Cell Rep 2018;24(2):271-277.
  3. Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol 2007;196(2):97-106.
  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. 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):3124-3132.
  6. Krajewski-Hall SJ, Miranda Dos Santos F, McMullen NT, et al. Glutamatergic neurokinin 3 receptor neurons in the median preoptic nucleus modulate heat-defense pathways in female mice. Endocrinology 2019;160(4):803-816.

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