The mechanism of VMS

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

Vasomotor Symptoms (VMS), also known as hot flushes and night sweats, aren’t caused by declining oestrogen alone. VMS result from altered activity of the kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the temperature control centre of the hypothalamus.2-4

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.2,5,6

kidney-beans
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.2,5,7

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 signaling causes heightened KNDy neuronal activity, which leads to hypertrophy of KNDy neurons and altered activity on the temperature control centre.2,5,7

Inside the source of a hot flush

Inside the source of a hot flush

As a result, the temperature control centre triggers heat dissipation effectors that cascade into VMS, also referred to as hot flushes and night sweats.2,5,7

Brain with a cross section of the hypothalamus highlighted.

Watch how it works

Middle-aged menopausal Hispanic woman looking down, with light reflecting on her perspiration.

Not an actual patient.

VMS in her words

I never know when they're coming. I just have to suffer through them when they happen.

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Uncover the burden of VMS
See how VMS result from altered activity in the hypothalamus

References:

  1. Monteleone P, Mascagni G, Giannini A, Genazzani AR, Simoncini T. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol 2018;14(4):199-215.
  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. 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. Modi M, Dhillo WS. Neurokinin 3 receptor antagonism: a novel treatment for menopausal hot flushes. Neuroendocrinology 2019;109(3):242-8.
  5. Krajewski-Hall SJ, Blackmore EM, McMinn JR, Rance NE. Estradiol alters body temperature regulation in the female mouse. Temperature 2018;5(1):56-69.
  6. 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.
  7. 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.