Advertisement

Postmenopausal Physiological Changes

  • Robert R. FreedmanEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 21)

Abstract

The hallmark of menopause is the marked reduction of estradiol levels due to ovarian failure. This, among other factors result in hot flashes, the most common menopausal symptom. Hot flashes (HFs) can be measured objectively, both inside and outside the laboratory, using sternal skin conductance, an electrical measure of sweating. We have found that HFs are triggered by small elevations in core body temperature (T C ), acting within a greatly reduced thermoneutral zone. This reduction is caused by elevated central sympathetic activation, among other factors. There is a circadian rhythm of HFs peaking at 1825 h. Imaging studies have shown that hot flash activation begins in the brainstem, followed by the insula and by the prefrontal cortex. HFs in the first, but not the second half of the night can produce awakenings and arousals. This is because rapid eye movement (REM) sleep suppresses thermoregulatory effector responses, which include hot flashes.

Keywords

Hot flash Menopause Sleep Thermoregulation 

Notes

Acknowledgments

This work was supported by NIH Merit Award, R37-AG05233 and by R01-MH63089.

References

  1. Ansonoff MA, Etgen AM (2001) Receptor phosphorylation mediates estradiol reduction of alpha 2-adrenoceptor coupling to G protein in the hypothalamus of female rats. Endocrine 14:165–174PubMedCrossRefGoogle Scholar
  2. Askel S, Schomberg DW, Tyrey L et al (1976) Vasomotor symptoms, serum estrogens, gonadotropin levels in surgical menopause. Am J Obstet Gynecol 126:165–169Google Scholar
  3. Brück K, Zeisberger E (1990) Adaptive changes in thermoregulation and their neuropharmacological basis. In: Schönbaum E, Lomax P (eds) Thermoregulation: physiology and biochemistry. Pergamon, New York, pp 255–307Google Scholar
  4. Carpenter JS, Gilchrist JM, Chen K et al (2004) Hot flashes, core body temperature, and metabolic parameters in breast cancer survivors. Menopause 11:375–381PubMedCrossRefGoogle Scholar
  5. Casper RF, Yen SSC (1981) Menopausal flushes: effect of pituitary gonadotropin desensitization by a potent luteinizing hormone releasing factor agonist. J Clin Endocrinol Metab 53:1056–1058PubMedCrossRefGoogle Scholar
  6. Casper RF, Yen SSC, Wilkes MM (1979) Menopausal flushes: a neuroendocrine link with pulsatile luteinizing hormone secretion. Science 204:823–825CrossRefGoogle Scholar
  7. Charney DS, Heninger GR, Sternberg DE (1982) Assessment of α2-adrenergic autoreceptor function in humans: effects of oral yohimbine. Life Sci 30:2033–2041PubMedCrossRefGoogle Scholar
  8. de Bakker IPM, Everaerd W (1996) Measurement of menopausal hot flushes: validation and cross-validation. Maturitas 24:87–98CrossRefGoogle Scholar
  9. DeFazio J, Meldrum DR, Laufer L et al (1983) Induction of hot flashes in premenopausal women treated with a long-acting GnRH agonist. J Clin Endocrinol Metab 56:445–448PubMedCrossRefGoogle Scholar
  10. DeFazio J, Vorheugen C, Chetkowski R et al (1984) The effects of naloxone on hot flashes and gonadotropin secretion in postmenopausal women. J Clin Endocrinol Metab 58:578–581PubMedCrossRefGoogle Scholar
  11. Diwadkar VA, Murphy ER, Freedman RR (2013) Temporal sequencing of brain activations during naturally occurring thermoregulatory events. Cereb cortex Jun 19 [Epub ahead of print]Google Scholar
  12. Etgen AM, Ansonoff MA, Quesada A (2001) Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for female reproductive physiology. Horm Behav 40:169–177PubMedCrossRefGoogle Scholar
  13. Feldman BM, Voda A, Groseth E (1985) The prevalence of hot flash and associated variables among perimenopausal women. Res Nurs Health 8:261–268PubMedCrossRefGoogle Scholar
  14. Freedman RR (1989) Laboratory and ambulatory monitoring of menopausal hot flashes. Psychophysiology 26:573–579PubMedCrossRefGoogle Scholar
  15. Freedman RR (1998) Biochemical, metabolic, and vascular mechanisms in menopausal hot flushes. Fertil Steril 70:1–6CrossRefGoogle Scholar
  16. Freedman RR (2009) Patient satisfaction with miniature, ambulatory, postmenopausal hot flash recorder. Open Med Devices J 1:1–2Google Scholar
  17. Freedman RR (2010) Objective or subjective measurement of hot flashes in clinical trials: Quo Vadis. Maturitas 67:99–100PubMedCrossRefGoogle Scholar
  18. Freedman RR, Blacker CM (2002) Estrogen raises the sweating threshold in postmenopausal women with hot flashes. Fertil Steril 77:487–490PubMedCrossRefGoogle Scholar
  19. Freedman RR, Dinsay R (2000) Clonidine raises the sweating threshold in symptomatic but not in asymptomatic postmenopausal women. Fertil Steril 74:20–23PubMedCrossRefGoogle Scholar
  20. Freedman RR, Krell W (1999) Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol 181:66–70PubMedCrossRefGoogle Scholar
  21. Freedman RR, Roehrs TA (2004) Lack of sleep disturbance from menopausal hot flashes. Fertil Steril 82:138–144PubMedCrossRefGoogle Scholar
  22. Freedman RR, Roehrs TA (2006) Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance. Menopause 13:576–583PubMedCrossRefGoogle Scholar
  23. Freedman RR, Roehrs TA (2007) Sleep disturbance in menopause. Menopause 14:826–829PubMedCrossRefGoogle Scholar
  24. Freedman RR, Wasson S (2007) Miniature, hygrometric hot flash recorder. Fertil Steril 88:494–496PubMedCentralPubMedCrossRefGoogle Scholar
  25. Freedman RR, Woodward S (1995) Altered shivering threshold in postmenopausal women with hot flashes. Menopause 2:163–168Google Scholar
  26. Freedman RR, Woodward S (1996) Core body temperature during menopausal hot flushes. Fertil Steril 65:1141–1144PubMedGoogle Scholar
  27. Freedman RR, Woodward S, Sabharwal SC (1990) Adrenergic mechanism in menopausal hot flushes. Obstet Gynecol 76:573–578PubMedGoogle Scholar
  28. Freedman RR, Woodward S, Norton D (1992) Laboratory and ambulatory monitoring of menopausal hot flushes: comparison of symptomatic and asymptomatic women. J Psychophysiol 6:162–166Google Scholar
  29. Freedman RR, Norton D, Woodward S et al (1995) Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab 80:2354–2358PubMedGoogle Scholar
  30. Freedman RR, Benton MD, Genik RJ II et al (2006) Cortical activation during menopausal hot flashes. Fertil Steril 85:674–678PubMedCrossRefGoogle Scholar
  31. Freedman RR, Kruger ML, Wasson SL (2011) Heart rate variability in menopausal hot flashes during sleep. Menopause 18:1–4CrossRefGoogle Scholar
  32. Gambone J, Meldrum DR, Laufer L et al (1984) Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes. J Clin Endocrinol Metab 59:1097–1102PubMedCrossRefGoogle Scholar
  33. Ginsburg J, Swinhoe J, O’Reilly B (1981) Cardiovascular responses during the menopausal hot flush. Br J Obstet Gynaecol 88:925–930PubMedCrossRefGoogle Scholar
  34. Gold EB, Colvin A, Avis N et al (2006) Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women’s health across the nation. Am J Pub Health 96:1–10CrossRefGoogle Scholar
  35. Goldberg M, Robertson D (1983) Yohimbine: a pharmacological probe for study of α2-adrenoceptor. Pharmacol Rev 35:143–180PubMedGoogle Scholar
  36. Hanisch LJ, Palmer SC, Donahue A et al (2007) Validation of sternal skin conductance for detection of hot flashes in prostate cancer survivors. Psychophysiol 44:189–193CrossRefGoogle Scholar
  37. Insel PA, Motulsky HJ (1987) Physiologic and pharmacologic regulation of adrenergic receptors. In: Insel PA (ed) Adrenergic receptors in man. Marcel Dekker, New York, pp 201–236Google Scholar
  38. Jeffcoate SL (1981) Climacteric flushing: clinical and endocrine response to infusion of naloxone. Br J Obstet Gynaecol 88:919–924PubMedCrossRefGoogle Scholar
  39. Kopin IJ, Blombery P, Ebert MH et al (1984) Disposition and metabolism of MHPG-CD3 in humans: plasma MHPG as the principal pathway of norepinephrine metabolism and as an important determinant in CSF levels of MHPG. In: Usdin E et al (eds) Frontiers in biochemical and pharmacological research in depression. Raven, New York, pp 57–68Google Scholar
  40. Kravitz HM, Ganz PA, Bromberger J et al (2003) Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause 10:19–28PubMedGoogle Scholar
  41. Kronenberg F (1990) Hot flashes: epidemiology and physiology. Ann N Y Acad Sci 592:52–86PubMedCrossRefGoogle Scholar
  42. Kronenberg F, Cote LJ, Linkie DM et al (1984) Menopausal hot flashes: thermoregulatory, cardiovascular, and circulating catecholamine and LH changes. Maturitas 6:31–43PubMedCrossRefGoogle Scholar
  43. Meldrum DR, Erlik Y, Lu JKH et al (1981) Objectively recorded hot flushes in patients with pituitary insufficiency. J Clin Endocrinol Metab 52:684–687PubMedCrossRefGoogle Scholar
  44. Molnar GW (1975) Body temperature during menopausal hot flashes. J Appl Physiol: Respir Environ Exerc Physiol 38:499–503Google Scholar
  45. Mulley G, Mitchell RA, Tattersall RB (1977) Hot flushes after hypophysectomy. BMJ 2:1062PubMedCentralPubMedCrossRefGoogle Scholar
  46. North American Menopause Society (2007) Menopause practice: a clinician’s guide. Normal physiology, pp 19–27Google Scholar
  47. Sastre M, Garcia-Sevilla JA (1994) Density of alpha-2A adrenoceptors and Gi proteins in the human brain: ratio of high-affinity agonist sites to antagonist sites and effect of age. J Pharmacol Exp Ther 269:1062–1072PubMedGoogle Scholar
  48. Savage MV, Brengelmann GL (1996) Control of skin blood flow in the neutral zone of human body temperature regulation. J Appl Physiol 80:1249–1257PubMedGoogle Scholar
  49. Schindler AE, Muller D, Keller E et al (1979) Studies with clonidine (Dixarit) in menopausal women. Arch Gynecol 227:341–347PubMedCrossRefGoogle Scholar
  50. Starke K, Gothert M, Kilbringer H (1989) Modulation of neurotransmitter release of presynaptic autoreceptors. Physiol Rev 69:864–989PubMedGoogle Scholar
  51. Stone AA, Shiffman S, Schwartz JE et al (2003) Patient compliance with paper and electronic diaries. Control Clin Trials 24:182–199PubMedCrossRefGoogle Scholar
  52. Takarangi MK, Garry M, Loftus EF (2006) Dear diary, is plastic better than paper? I can’t remember. Comment on Green, Bolger, Shrout, and Reis. Psychol Methods 11:119–122PubMedCrossRefGoogle Scholar
  53. Tataryn IV, Meldrum DR, Lu KH et al (1979) FSH, and skin temperature during menopausal hot flush. J Clin Endocrinol Metab 49:152–154PubMedCrossRefGoogle Scholar
  54. Tataryn IV, Lomax P, Bajorek JG et al (1980) Postmenopausal hot flushes: a disorder of thermoregulation. Maturitas 2:101–107PubMedCrossRefGoogle Scholar
  55. Young T, Rabago D, Zgierska A et al (2003) Objective and subjective sleep quality in premenopausal, perimenopausal, and postmenopausal women in the Wisconsin Sleep Cohort Study. Sleep 26:667–672PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Departments of Psychiatry and Behavioral Neurosciences and Obstetrics and GynecologyWayne State University School of MedicineDetroitUSA

Personalised recommendations