Skip to main content
Log in

Mechanism of hot flashes

  • Educational Series
  • Molecular and Cellular Biology of Cancer
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Hot flashes are a common and disturbing adverse effect of hormonal therapy for cancer. Their pathophysiology is poorly understood. At present, the leading mechanistic hypothesis rests on the assumption that abrupt hormone deprivation will result in loss of negative feedback over hypothalamic noradrenaline synthesis. In this article we critically review the different theories used to explain this phenomenon. A better understanding of the pathophysiology of hot flashes may facilitate the development of new therapeutic approaches.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Huggins C, Hodges GV (1941) Studies on prostate cancer. I. The effect of castration, estrogen and androgen injections on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293–295

    CAS  Google Scholar 

  2. Charig CR, Rundle JS (1989) Flushing. Longterm side effects of orchidectomy in treatment of prostatic cancer. Urology 33:175–178

    Article  PubMed  CAS  Google Scholar 

  3. Maatman TJ, Gupta MK, Montie JE (1985) Effectiveness of castration vs intravenous estrogen in producing rapid endocrine control of metastatic cancer of prostate. J Urol 133:620–621

    PubMed  CAS  Google Scholar 

  4. Aksel S, Schomberg DW, Tyrey L, Hammond CB (1976) Vasomotor symptoms, serum estrogens, and gonadotropin levels in surgical menopause. Am J Obstet Gynecol 126:165–169

    PubMed  CAS  Google Scholar 

  5. Buchholz NP, Matarelli G (1994) Hot flushes after orchidectomy in treatment of prostate cancer: a serious effect. Z Gerontol 27:334–336

    PubMed  CAS  Google Scholar 

  6. Harvey H, Lipton A, Max D et al (1985) Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer. J Clin Oncol 3:1068–1072

    PubMed  CAS  Google Scholar 

  7. Leuprolide Study Group (1984) Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med 311:1281–1286

    Article  Google Scholar 

  8. Sarosdy MF, Schellhammer PF, Soloway MS et al (1999) Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer. BJU Int 83:801–806

    Article  PubMed  CAS  Google Scholar 

  9. Parmar H, Edwards L, Phillips RH et al (1987) Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer. Br J Urol 59:248–254

    Article  PubMed  CAS  Google Scholar 

  10. Nishiyama T, Kanazawa S, Watanabe R et al (2004) Influence of hot flashes on quality of life in patients with prostate cancer treated with androgen deprivation therapy. Int J Urol 11:735–741

    Article  PubMed  Google Scholar 

  11. Carpenter JS, Gilchrist JM, Chen K et al (2004) Hot flashes, core body temperature and metabolic parameters in breast cancer survivors. Menopause 11:375–381

    Article  PubMed  Google Scholar 

  12. Albertazzi P (2006) Noradrenergic and serotonergic modulation to treat vasomotor symptoms. J Br Menopause Soc 12:7–11

    Article  PubMed  Google Scholar 

  13. Molnar GW (1975) Body temperature during menopausal hot flashes. J Appl Physiol 38:499–503

    PubMed  CAS  Google Scholar 

  14. Kronenberg FL, Cote LJ, Linkie DM et al (1984) Menopausal hot flashes: thermoregulatory, cardiovascular and circulating catecholamine and LH changes. Maturitas 6:31–43

    Article  PubMed  CAS  Google Scholar 

  15. Freedman RR (2005) Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med 118[Suppl]:124–130

    Article  PubMed  Google Scholar 

  16. Carpenter JS, Andrykowski MA, Freedman RR, Munn R (1999) Feasibility and psychometrics of an ambulatory hot flash monitoring device. Menopause 6:209–215

    Article  PubMed  CAS  Google Scholar 

  17. Kouriefs C, Georgiou M, Ravi R (2002) Hot flushes and prostate cancer: pathogenesis and treatment. BJU Int 89:379–383

    Article  PubMed  CAS  Google Scholar 

  18. Melldrum DR, Defazio JD, Erlik Y et al (1984) Pituitary hormones during the menopausal hot flash. Obstet Gynecol 64:752–756

    Google Scholar 

  19. Casper RF, Yen SS, Wilkes MM (1979) Menopausal flushes: a neuroendocrine link with pulsatile luteinizing hormone secretion. Science 205:823–825

    Article  PubMed  CAS  Google Scholar 

  20. Tataryn IV, Meldrum DR, Lu KH et al (1979) LH, FSH and skin temperature during the menopausal hot flush. J Endocrinol Metab 49:152–154

    Article  CAS  Google Scholar 

  21. Linsell CR, Lightman SL (1983) Postmenopausal flashes: studies of chronological organisation. Psychoneuroendocrinology 8:435–440

    Article  PubMed  CAS  Google Scholar 

  22. Freedman RR (2001) Physiology of hot flashes. Am J Hum Biol 13:453–464

    Article  PubMed  CAS  Google Scholar 

  23. Freedman RR, Woodward S, Sabharwal SC (1990) 2-Adrenergic mechanism in menopausal hot flushes. Obstet Gynecol 76:573–578

    PubMed  CAS  Google Scholar 

  24. 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 40:169–177

    Article  PubMed  CAS  Google Scholar 

  25. de Boer H, van Gastel P, van Sorge A (2009) Luteinizing hormone-releasing hormone and postmenopausal flushing. N Engl J Med 361:1218–1219

    Article  PubMed  Google Scholar 

  26. Freedman RR, Krell W (1999) Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol 18:66–70

    Article  Google Scholar 

  27. Dacks PA, Rance NE (2010) Effects of estradiol on the thermoneutral zone and core temperature in ovariectomized rats. Endocrinology 151:1187–1193

    Article  PubMed  CAS  Google Scholar 

  28. Paul SM, Axelrod J (1977) Catechol estrogen: presence in brain and endocrine tissues. Science 197:657–659

    Article  PubMed  CAS  Google Scholar 

  29. Stubbs WA, Jones A, Edwards CRW et al (1978) Hormonal and metabolic responses to an enkephalin analogue in normal man. Lancet 2:1225–1227

    Article  PubMed  CAS  Google Scholar 

  30. Tulandi T, Kinch RA, Guyda H et al (1985) Effect of naloxone on menopausal flushes, skin temperature, and luteinizing hormone secretion. Am J Obstet Gynecol 151:277–280

    PubMed  CAS  Google Scholar 

  31. Fishman J, Norton BI, Hahn EF (1980) Opiate regulation of estradiol-2-hydroxylase in brains of male rats: mechanism for control of pituitary hormone secretion. Proc Natl Acad Sci U S A 77:2574–2576

    Article  PubMed  CAS  Google Scholar 

  32. Savage MV, Brengelman GL (1996) Control of skin blood flow in the neutral zone of human body temperature regulation. J Appl Physiol 80:1249–1257

    PubMed  CAS  Google Scholar 

  33. Berendsen HHG (2000) The role of serotonine in hot flushes. Maturitas 36:155–164

    Article  PubMed  CAS  Google Scholar 

  34. Yasui T, Uemura H, Tomita J et al (2006) Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women. J Clin Endocrinol Metab 91:4805–4808

    Article  PubMed  CAS  Google Scholar 

  35. Noguchi M, Yuzurihara M, Kase Y et al (2008) Involvement of cytokine-induced neutrophil chemoattractant in hypothalamic thermoregulation of luteinizing hormone-releasing hormone. Endocrinology 149:2899–2906

    Article  PubMed  CAS  Google Scholar 

  36. Dunstan CA, Salafranca MN, Adhikari S et al (1996) Identification of two rat genes orthologous to the human interleukin-8 receptors. J Biol Chem 271:32770–32776

    Article  PubMed  CAS  Google Scholar 

  37. Guex-Crosier Y, Wittwer AJ, Roberge FG (1996) Intraocular production of a cytokine (CINC) responsible for neutrophil infiltration in endotoxin induced uveitis. Br J Ophthal 80:649–653

    Article  CAS  Google Scholar 

  38. Koike K, Sakamoto Y, Sawada T et al (1994) The production of CINC/gro, a member of the interleukin-8 family, in rat anterior pituitary gland. Biochem Biophys Res Commun 202:161–167

    Article  PubMed  CAS  Google Scholar 

  39. Noguchi M, Ikarashi Y, Yuzurihara M et al (2003) Significance of measured elevation of skin temperature induced by calcitonin gene-related peptide in anaesthetized rats. J Pharm Pharmacol 55:1547–1552

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Santiago Vilar-González.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vilar-González, S., Pérez-Rozos, A. & Cabanillas-Farpón, R. Mechanism of hot flashes. Clin Transl Oncol 13, 143–147 (2011). https://doi.org/10.1007/s12094-011-0633-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-011-0633-x

Keywords

Navigation