Our understanding of VMS is heating up

OUR UNDERSTANDING OF VMS IS HEATING UP

It’s not only about estrogen

Vasomotor Symptoms (VMS), also known as
hot flashes and night sweats, aren’t caused
by declining estrogen alone—we now know
that VMS result from unopposed neurokinin
B (NKB) signaling and altered activity of the
kisspeptin/neurokinin B/dynorphin (KNDy)
neurons in the temperature control center
of the hypothalamus.1-3

Brain with a cross section of the hypothalamus highlighted.
Brain with a cross section of the hypothalamus highlighted.

Inside the source of a hot flash

NKB and estrogen modulate KNDy neurons in a delicate balance, contributing to body temperature regulation. KNDy neurons are stimulated by NKB and inhibited by estrogen.2,4,5

Inside the source of a hot flash

Through the menopausal transition, estrogen declines, disrupting the balance with NKB.2,5,6

Inside the source of a hot flash

Unopposed, NKB signaling causes heightened KNDy neuronal activity, which leads to hypertrophy of KNDy neurons and altered activity on the thermoregulatory center.2,5,6

Inside the source of a hot flash

As a result, the thermoregulatory center triggers heat dissipation effectors that cascade into hot flashes and night sweats—VMS.2,6

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Middle age menopausal Latina woman

VMS IN HER WORDS

“It throws everything off kilter. [There
are] no rules on when or why they [hot
flashes] happen; they just happen.”

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. Thurston RC. Vasomotor symptoms. In: Crandall CJ, Bachman GA, Faubion SS, et al., eds. Menopause Practice: A Clinician’s Guide. 6th ed. Pepper Pike, OH: The North American Menopause Society, 2019:43-55. 4. 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. 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. 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.