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Frequently asked questions

Menopause is defined as the permanent cessation of menstrual periods. However, the symptoms of menopause can begin before the cessation of menses and extend over several years.1

 

Perimenopause, the transition from the reproductive period to the first year postmenopause, is associated with increasing symptom burden. This is due to the neurochemical changes in the central nervous system, which are associated with Vasomotor Symptoms (VMS), sleep disorders, and depression.1

 

Other symptoms can include changes in body shape related to cardiometabolic changes, musculoskeletal alterations, skin and urogenital atrophy, sexual dysfunction, osteoporosis, and sarcopenia.1

The main symptoms of menopause—and the most common reason women seek medical care during the menopausal transition—are hot flushes and night sweats, also known as vasomotor symptoms.2 Hot flushes are characterised by a sudden intense sensation of heat in the upper body, particularly the face, neck, and chest. Episodes of VMS typically last 1 to 5 minutes, and can be accompanied by perspiration, chills, anxiety, and heart palpitations. However, individual experiences of VMS vary.3

Oestrogen declines during menopause and is associated with various symptoms including VMS.1,4,5

 

In the case of VMS, we now know that during menopause, less oestrogen reaches the oestrogen receptors of kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which innervates the temperature control centre of the hypothalamus. The reduction in oestrogen alters the activity of the KNDy neurons, and that altered activity is one of the causes of VMS.4,5

VMS are physiological symptoms associated with menopause.3

 

In the thermoregulatory centre in the hypothalamus:

  • Neurokinin B (NKB) and oestrogen modulate KNDy neurons in a delicate balance, contributing to body temperature regulation. KNDy neurons are stimulated by NKB and inhibited by oestrogen.5-7
  • Through the menopausal transition, oestrogen declines, disrupting the balance with NKB.5,6,8
  • Unopposed, NKB signalling causes heightened KNDy neuronal activity, which leads to hypertrophy of KNDy neurons and altered activity on the thermoregulatory centre.5,6,8
  • As a result, the thermoregulatory centre triggers heat dissipation effectors that cascade into hot flushes and night sweats - VMS.5,8

Watch a hot flush in action

Studies have shown that the frequency and severity of VMS may be used as a predictor of chronic diseases in the future, such as cognitive impairment, cardiovascular disease, and osteoporosis.9

Current treatment classes for hot flushes and night sweats include hormone therapy (HT), which has long been the standard of care. Other treatment strategies include over-the-counter remedies like supplements and herbs.2

Up to 80% of women experience VMS during the menopausal transition.3 VMS last 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%).10,12

Not all women realise 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.12

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. Kaunitz AM, Manson JE. Management of menopausal symptoms. Obstet Gynecol 2015;126(4):859-876.
  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. Rapkin AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol 2007;196(2):97-106.
  5. Padilla SL, Johnson CW, Barker FD, et al. A neural circuit underlying the generation of hot flushes. Cell Rep 2018;24(2):271-277.
  6. Krajewski-Hall SJ, Blackmore EM, McMinn JR, Rance NE. Estradiol alters body temperature regulation in the female mouse. Temperature 2018;5(1):56-69.
  7. 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.
  8. Krajewski-Hall SJ, Dos Santos FM, 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.
  9. Biglia N, Cagnacci A, Gambacciani M, et al. Vasomotor symptoms in menopause: a biomarker of cardiovascular disease risk and other chronic diseases? Climacteric 2017;20(4):306-312.
  10. Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015;175(4):531-539.
  11. Williams RE, Levine KB, Kalilani L, et al. Menopause-specific questionnaire assessment in US population-based study shows negative impact on health-related quality of life. Maturitas 2009;62(2):153-159.
  12. Parish SJ, Nappi RE, Kingsberg S. Perspectives on counseling patients about menopausal hormone therapy: strategies in a complex data environment. Menopause 2018;25(8):937-949.
  13. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes 2005;3:47.

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