Skip to main content
SpringerLink
Log in
Book cover

Menopause pp 69–78Cite as

Clinical Symptoms and Quality of Life: Hot Flashes and Mood

  • Chapter
  • First Online:

Abstract

Hot flushes and night sweats are the predominant symptoms of menopause and usually they are referred as vasomotor symptoms. The mechanisms of increases in skin blood flow during hot flushes may include the withdrawal of sympathetic vasoconstrictor activity, increases in sympathetic cholinergic vasodilator activity, or a combination of both neural mechanisms and nonneural factors, with increased white matter hyperintensities suggesting that the relationship between hot flashes and cardiovascular risk observed in the periphery may extend to the brain.

The impact of vasomotor symptoms on mood and quality of life may be considerable and is often underestimated. Vasomotor symptoms were associated with decreased health-related quality of life and baseline depression and obesity amplified this negative association. Hormonal therapy reduces the frequency and severity of hot flushes, with health benefits when started near menopause, particularly for women with early menopause. Several nonhormonal therapies including antidepressed drugs were also found effective for hot flushes over placebo.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Matthews KA, Bromberger JT. Does the menopausal transition affect health-related quality of life? Am J Med. 2005;118:25–36.

    Article  PubMed  Google Scholar 

  2. Schneider HPG. The quality of life in the post-menopausal woman. Best Pract Res Clin Obstet Gynaecol. 2002;16:395–409.

    Article  PubMed  Google Scholar 

  3. Ayers B, Hunter MS. Health-related quality of life of women with menopausal hot flushes and night sweats. Climacteric. 2013;16:235–9.

    Article  CAS  PubMed  Google Scholar 

  4. Katon JG, Gray KE, Gerber MR, Harrington LB, Woods NF, Weitlauf JC, et al. Vasomotor symptoms and quality of life among Veteran and non-Veteran postmenopausal women. Gerontologist. 2016;56(Suppl 1):S40–53.

    Article  PubMed  Google Scholar 

  5. Archer DF, Sturdee DW, Baber R, de Villiers TJ, Pines A, Freedman RR, et al. Menopausal hot flushes and night sweats: where are we now? Climacteric. 2011;14:515–28.

    Article  CAS  PubMed  Google Scholar 

  6. Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015;175:531–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ziv-Gal A, Flaws JA. Factors that may influence the experience of hot flushes by healthy middle-aged women. J Womens Health (Larchmt). 2010;19:1905–14.

    Article  Google Scholar 

  8. Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, et al. 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 Public Health. 2006;96:1226–35.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric. 2007;10:197–214.

    Article  CAS  PubMed  Google Scholar 

  10. Andrikoula M, Prelevic G. Menopausal hot flushes revisited. Climacteric. 2009;12:3–15.

    Article  CAS  PubMed  Google Scholar 

  11. Palacios S, Henderson VW, Siseles N, Tan D, Villaseca P. Age of menopause and impact of climacteric symptoms by geographical region. Climacteric. 2010;13:419–28.

    Article  CAS  PubMed  Google Scholar 

  12. Voda AM. Climacteric hot flash. Maturitas. 1981;3:73–90.

    Article  CAS  PubMed  Google Scholar 

  13. Wilkin JK. Why is flushing limited to a mostly facial cutaneous distribution? J Am Acad Dermatol. 1988;19(2 Pt 1):309–13.

    Article  CAS  PubMed  Google Scholar 

  14. Freedman RR, Woodward S, Mayes MM. Nonneural mediation of digital vasodilation during menopausal hot flushes. Gynecol Obstet Investig. 1994;38:206–9.

    Article  CAS  Google Scholar 

  15. Freedman RR, Woodward S. Behavioral treatment of menopausal hot flushes: evaluation by ambulatory monitoring. Am J Obstet Gynecol. 1992;167:436–9.

    Article  CAS  PubMed  Google Scholar 

  16. Freedman RR, Woodward S. Core body temperature during menopausal hot flushes. Fertil Steril. 1996;65:1141–4.

    Article  CAS  PubMed  Google Scholar 

  17. Rance NE, Young WS III. Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women. Endocrinology. 1991;128:2239–47.

    Article  CAS  PubMed  Google Scholar 

  18. Rance NE, McMullen NT, Smialek JE, Price DL, Young WS III. Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus. J Clin Endocrinol Metab. 1990;71:79–85.

    Article  CAS  PubMed  Google Scholar 

  19. Goodman RL, Lehman MN, Smith JT, Coolen LM, de Oliveira CVR, Jafarzadehshirazi MR, et al. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology. 2007;148:5752–60.

    Article  CAS  PubMed  Google Scholar 

  20. Rometo AM, Krajewski SJ, Voytko ML, Rance NE. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab. 2007;92:2744–50.

    Article  CAS  PubMed  Google Scholar 

  21. Rometo AM, Voytko ML, Rance NE. Hypertrophy of neurons expressing dynorphin mRNA within the arcuate nucleus of young ovariectomized monkeys. Soc Neurosci Abstr. 2005;31:755–9.

    Google Scholar 

  22. Abel TW, Voytko ML, Rance NE. The effects of hormone replacement therapy on hypothalamic neuropeptide gene expression in a primate model of menopause. J Clin Endocrinol Metab. 1999;84:2111–8.

    CAS  PubMed  Google Scholar 

  23. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349:1614–27.

    Article  CAS  PubMed  Google Scholar 

  24. de Roux N, Genin E, Carel J-C, Matsuda F, Chaussain J-L, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100:10972–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009;41:354–8.

    Article  CAS  PubMed  Google Scholar 

  26. Rance NE, Krajewski SJ, Smith MA, Cholanian M, Dacks PA. Neurokinin B and the hypothalamic regulation of reproduction. Brain Res. 2010;1364:116–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lehman MN, Coolen LM, Goodman RL. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arucate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology. 2010;151:3479–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wakabayashi Y, Nakada T, Murata K, Ohkura S, Mogi K, Navarro VM, 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;30:3124–32.

    Article  CAS  PubMed  Google Scholar 

  29. Han SY, McLennan T, Czieselsky K, Herbison AE. Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion. Proc Natl Acad Sci U S A. 2015;112:13109–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Casper RF, Yen SSC, Wilkes MM. Menopausal flushes: a neuroendocrine link with pulsatile luteinizing hormone secretion. Science. 1979;205:823–5.

    Article  CAS  PubMed  Google Scholar 

  31. Rance NE, Dacks PA, Mittelman-Smith MA, Romanovsky AA, Krajewski-Hall SJ. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013;34:211–27.

    Article  CAS  PubMed  Google Scholar 

  32. Krajewski SJ, Burke MC, Anderson MJ, McMullen NT, Rance NE. Forebrain projections of arcuate neurokinin B neurons demonstrated by anterograde tract-tracing and monosodium glutamate lesions in the rat. Neuroscience. 2010;166:680–97.

    Article  CAS  PubMed  Google Scholar 

  33. Nakamura K, Morrison SF. A thermosensory pathway mediating heat-defense responses. Proc Natl Acad Sci U S A. 2010;107:8848–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dacks PA, Krajewski SJ, Rance NE. Activation of neurokinin 3 receptors in the median preoptic nucleus decreases core temperature in the rat. Endocrinology. 2011;152:4894–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mittelman-Smith MA, Williams H, Krajewsk-Hall SJ, McMullen NT, Rance NE. Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci U S A. 2012;109:19846–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mittelman-Smith MA, Krajewski-Hall SJ, McMullen NT, Rance NE. Neurokinin 3 receptor-expressing neurons in the median preoptic nucleus modulate heat-dissipation effectors in the female rat. Endocrinology. 2015;156:2552–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jayasena CN, Comninos AN, Stefanopoulou E, Buckley A, Narayanaswamy S, Izzi-Engbeaya C, et al. Neurokinin B administration induces hot flushes in women. Sci Rep. 2015;5:8466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Crandall CJ, Manson JE, Hohensee C, Horvath S, Wactawski-Wende J, LeBlanc ES, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s Health Initiative study. Menopause. 2017;24:252–61.

    Article  PubMed  Google Scholar 

  39. Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Nash Z, et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017;389:1809–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fraser GL, Depypere H, Timmerman D, Donders G, Sieprath P, Ramael S, et al. Clinical evaluation of the NK3 receptor Antagonist Fezolinetant (a.k.a. ESN364) for the treatment of menopausal hot flashes. Endocrine Society Abstracts. 2017;38(3).

    Google Scholar 

  41. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn ovarian aging study cohort. Menopause. 2014;21:924–32.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Duffy OK, Iversen L, Aucott L, Hannaford PC. Factors associated with resilience or vulnerability to hot flushes and night sweats during the menopausal transition. Menopause. 2013;20:383–92.

    PubMed  Google Scholar 

  43. Pérez-López FR, Pérez-Roncero G, Fernández-Iñarrea J, Fernández-Alonso AM, Chedraui P, Llaneza P. Resilience, depressed mood, and menopausal symptoms in postmenopausal women. Menopause. 2014;21:159–64.

    Article  PubMed  Google Scholar 

  44. Llaneza P, González C, Fernandez-Iñarrea J, Alonso A, Arnott I, Ferrer-Barriendos J. Insulin resistence and health-related quality of life in postmenopausal women. Fertil Steril. 2009;91(4 Suppl):1370–3.

    Article  PubMed  Google Scholar 

  45. Sarrel P, Portman D, Lefebvre P, Lafeuille M-H, Grittner AM, Fortier J, et al. Incremental direct and indirect costs of untreated vasomotor symptoms. Menopause. 2015;22:260–6.

    Article  PubMed  Google Scholar 

  46. Gordon JL, Rubinow DR, Thurston RC, Paulson J, Schmidt PJ, Girdler SS. Cardiovascular, hemodynamic, neuroendocrine, and inflammatory markers in women with and without vasomotor symptoms. Menopause. 2016;23:1189–98.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Thurston RC, Aizenstein HJ, Derby CA, Sejdic E, Maki PM. Menopausal hot flashes and white matter hyperintensities. Menopause. 2016;23:27–32.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Worsley R, Bell R, Kulkarni J, Davis SR. The association between vasomotor symptoms and depression during perimenopause: a systematic review. Maturitas. 2014;77:111–7.

    Article  PubMed  Google Scholar 

  50. de Kruif M, Spijker AT, Molendijk ML. Depression during the perimenopause: a meta-analysis. J Affect Disord. 2016;206:174–80.

    Article  PubMed  Google Scholar 

  51. Burleson MH, Todd M, Trevathan WR. Daily vasomotor symptoms, sleep problems, and mood: using daily data to evaluate the domino hypothesis in middle-aged women. Menopause. 2010;17:87–95.

    Article  PubMed  Google Scholar 

  52. Pinkerton JV, Abraham L, Bushmakin AG, Cappelleri JC, Komm BS. Relationship between changes in vasomotor symptoms and changes in menopause-specific quality of life and sleep parameters. Menopause. 2016;23:1060–6.

    Article  PubMed  Google Scholar 

  53. Smith DJ, Kyle S, Forty L, Cooper C, Walters J, Russell E, et al. Differences in depressive symptom profile between males and females. J Affect Disord. 2008;108:279–84.

    Article  PubMed  Google Scholar 

  54. Unsal A, Tozun M, Ayranci U. Prevalence of depression among postmenopausal women and related characteristics. Climacteric. 2011;14:244–51.

    Article  CAS  PubMed  Google Scholar 

  55. Llaneza P, García-Portilla MP, Llaneza-Suárez D, Armott B, Pérez-López FR. Depressive disorders and the menopause transition. Maturitas. 2012;71:120–30.

    Article  PubMed  Google Scholar 

  56. Freeman EW. Associations of depression with the transition to menopause. Menopause. 2010;17:823–7.

    Article  PubMed  Google Scholar 

  57. Kaufert PA, Gilbert P, Tate R. The Manitoba project: a re-examination of the link between menopause and depression. Maturitas. 1992;61:54–66.

    Article  Google Scholar 

  58. Vivian-Taylor J, Hickey M. Menopause and depression: is there a link? Maturitas. 2014;79:142–6.

    Article  PubMed  Google Scholar 

  59. Gibson CJ, Thurston RC, Bromberger JT, Kamarck T, Matthews KA. Negative affect and vasomotor symptoms in the study of women’s health across the nation daily hormone study. Menopause. 2011;18:1270–7.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Seritan AL, Iosif A-M, Park JH, DeatherageHand D, Sweet RL, Gold EB. Self-reported anxiety, depressive, and vasomotor symptoms. Menopause. 2010;17:410–5.

    Article  PubMed  Google Scholar 

  61. Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition. Arch Gen Psychiatry. 2006;63:385.

    Article  PubMed  Google Scholar 

  62. Nathorst-Böös J, von Schoultz B, Carlström K. Elective ovarian removal and estrogen replacement therapy—effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol. 1993;14:283–93.

    Article  PubMed  Google Scholar 

  63. Kronenberg F. Hot flashes: epidemiology and physiology. Ann N Y Acad Sci. 1990;592:52–86.

    Article  CAS  PubMed  Google Scholar 

  64. Gibson CJ, Joffe H, Bromberger JT, Thurston RC, Lewis TT, Khalil N, et al. Mood symptoms after natural menopause and hysterectomy with and without bilateral oophorectomy among women in midlife. Obstet Gynecol. 2012;119:935–41.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kaunitz AM, Manson JE. Management of menopausal symptoms. Obstet Gynecol. 2015;126:859–76.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomized controlled trial. JAMA. 2002;288:321–33.

    Article  CAS  PubMed  Google Scholar 

  67. Rohan TE, Negassa A, Chlebowski RT, Habel L, McTiernan A, Ginsberg M, et al. Conjugated equine estrogen and risk of benign proliferative breast disease: a randomized controlled trial. J Natl Cancer Inst. 2008;100:563–71.

    Article  CAS  PubMed  Google Scholar 

  68. Pinkerton JV. Dose is important for nonhormonal therapy for hot flashes. BJOG. 2016;123:1744.

    Article  CAS  PubMed  Google Scholar 

  69. Wei D, Chen Y, Wu C, Wu Q, Yao L, Wang Q, et al. Effect and safety of paroxetine for vasomotor symptoms: systematic review and meta-analysis. BJOG. 2016;123:1735–43.

    Article  CAS  PubMed  Google Scholar 

  70. Freedman RR, Woodward S, Sabharwal SC. Alpha 2-adrenergic mechanism in menopausal hot flushes. Obstet Gynecol. 1990;76:573–8.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The help of Prof. N. Rance from the University of Arizona College of Medicine in the implication of the KNDy neurons in hot flushes is acknowledged.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Asturias Central University Hospital, University of Oviedo, Asturias, Spain

    Plácido Llaneza

Authors
  1. Plácido Llaneza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Plácido Llaneza .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Valencia, Spain

    Antonio Cano

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Llaneza, P. (2017). Clinical Symptoms and Quality of Life: Hot Flashes and Mood. In: Cano, A. (eds) Menopause. Springer, Cham. https://doi.org/10.1007/978-3-319-59318-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-59318-0_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-59317-3

  • Online ISBN: 978-3-319-59318-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation