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For too long, our understanding of Vasomotor Symptoms (VMS), also known as hot flashes and night sweats, has been limited to the role of estrogen alone. Finally, new science has revealed a more complete picture.1,2

We now know that VMS results from altered activity of the kisspeptin/neurokinin B/dynorphon (KNDy) neurons in the temperature control center of the hypothalamus1,3

Vasomotor Symptoms can be a serious medical condition associated with menopause.4

  • Inside the thermoregulatory center in the hypothalamus, specific neurons known as kisspeptin/neurokinin B/dynorphin neurons, or KNDy neurons, contribute to regulation of the body’s temperature3

  • KNDy neurons are inhibited by estrogen and stimulated by the neuropeptide neurokinin B (NKB) in a delicate balance5,6

  • 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 center3,5,7

  • As a result, the thermoregulatory center triggers heat dissipation effectors that are experienced as hot flashes and night sweats, or VMS3,7

Recent studies have shown that the frequency and severity of VMS may be used as a biomarker for chronic diseases in the future regarding cognitive impairment, cardiovascular disease, and bone health.8

Current FDA-approved treatment classes for hot flashes and night sweats include hormone therapy (HT) and SSRI.* Other treatment strategies include over-the-counter remedies like supplements and herbs. Each of these options has varying levels of efficacy and safety.9

Even though HT has long been the standard of care, new science suggests that estrogen is not the only cause of VMS.1,2

*SSRI=selective serotonin reuptake inhibitor.

In the US, up to 80% of women are affected by VMS during the menopausal transition.4 VMS lasts for a median duration of 7.4 years, and women living with VMS reported a negative impact on sleep (82%), mood (69%), concentration (69%), energy (63%), sexual activity (41%), work (46%), social activities (44%), and leisure activities (48%).10

However, not all women experience VMS to the same extent—in the US, VMS affects a higher percentage of African American and Hispanic women, 46% and 34%, respectively, vs 31% of White women. In addition, African American women and Hispanic women experience symptoms for 2-4 years longer than White women.11,12

Not all women realize that VMS are a medical condition worthy of discussion, therefore many go undiagnosed or untreated.12,13 Having a productive dialogue is crucial in helping women impacted by VMS. Studies show that women want to have open and honest conversations about menopause symptoms and treatment options with their doctor.13

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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. Modi M, Dhillo WS. Neurokinin 3 receptor antagonism: a novel treatment for menopausal hot flushes. Neuroendocrinology 2019;109(3):242-8. 3. 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. 4. 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. 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. 8. Biglia N, Cagnacci A, Gambacciani M, Lello S, Maffei S, Nappi RE. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017;20(4):306-12. 9. Kaunitz AM, Manson JE. Management of menopausal symptoms. Obstet Gynecol 2015;126(4):859-76. 10. Williams RE, Levine KB, Kalilani L, Lewis J, Clark RV. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 2009;62(2):153-9. 11. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175(4):531-9. 12. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes 2005;3:47. 13. Parish SJ, Nappi RE, Kingsberg S. Perspectives on counseling patients about menopausal hormone therapy: strategies in a complex data environment. Menopause 2018;25(8):937-49.


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