Pathophysiology of Menopausal Hot Flushes

  • Howard L. Judd


In women, the most common and characteristic symptom of the climacteric is an episodic disturbance consisting of sudden flushing and perspiration, referred to as a “hot flush or flash.” It has been observed in 65–76% of women who go through the physiological menopause or have a bilateral ovariectomy (Hannan, 1927; Neugarten and Kraines, 1965; Jaszmann et al., 1969; Thompson et al.,1973; McKinlay and Jeffreys, 1974). Of those having flushes, 82% will experience the disturbance for more than 1 year (Jaszmann et al.,1969) and 25–50% will complain of the symptom for more than 5 years (Neugarten and Kraines, 1965; Thompson et al., 1973). Although hot flushes occur in millions of women, there have been few attempts to understand the pathophysiology of this symptom until recently.


Luteinizing Hormone Skin Temperature GnRH Neuron Cutaneous Vasodilation Finger Temperature 
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  1. Abe, T., Fuguhashi, N., Yamaya, Y., Wada, Y., Hoshiai, A., and Suzuki, M., 1977, Correlation between climacteric symptoms and serum levels of estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone, Am. J. Obstet. Gynecol. 123: 65–67.Google Scholar
  2. Aitken, J. M., Davidson, A., England, P., Govan, A. D. T., Hart, D. M., Kelly, A., Lindsay, R., and Moffatt, A., 1974, The relationship between menopausal vasomotor symptoms and gonadotropin excretion in urine after oophorectomy, J. Ob/Gyn. Brit. Commun. 81: 150–154.Google Scholar
  3. Aksel, S., Schomberg, D. W., Tyrey, L., and Hammond, C. B., 1976, Vasomotor symptoms, serum estrogens, and gonadotropin levels in surgical menopause, Am. J. Obstet. Gynecol. 126: 165–169.PubMedGoogle Scholar
  4. Albeaux-Fernet, M., and Deribreux, J., 1946, La bouffee de chaleur symptome majeur de la menopause, Semaine Hop. (Paris) 22: 1500–1502.Google Scholar
  5. Albrecht, B. H., Schiff, I., Tulchinsky, D., and Ryan, K. J., 1981, Objective evidence that placebo and oral medroxyprogesterone acetate therapy diminish menopausal vasomotor flushes, Am. J. Obstet. Gynecol. 139: 631–635.PubMedGoogle Scholar
  6. Antunes, C. M., Stolley, P. D., Rosenshein, N. B., Davies, J. L., Tonascia, J. A., Brown, C., Burnett, L., Rutledge, A., Pokempner, M., and Garcia, R., 1979, Endometrial cancer and estrogen use, N. Engl. J. Med. 300: 9–13.PubMedCrossRefGoogle Scholar
  7. Bardin, C. W., and Lipsett, M. B., 1967, Testosterone and androstenedione blood production rates in normal women and women with idiopathic hirsutism or polycystic ovaries, J. Clin. Invest. 46: 891–902.PubMedCrossRefGoogle Scholar
  8. Barr, W., 1975, Problems related to postmenopausal women, S. Afr. Med. J. 49: 437–439.PubMedGoogle Scholar
  9. Bhattacharya, A. N., Dierschke, D. J., Yamaji, T., and Knobil, E., 1972, The pharmacologic blockade of the circhoral mode of LH secretion in the ovariectomized rhesus monkey, Endocrinology 90: 778–786.PubMedCrossRefGoogle Scholar
  10. Bligh, J., 1973, Temperature Regulation in Mammals and Other Vertebrates, North-Holland Publishing, Amsterdam.Google Scholar
  11. Bolli, P., and Simpson, F. O., 1975, Clonidine in menopausal flushing: A double blind trial, New Zealand Med. J. 82: 196–197.PubMedGoogle Scholar
  12. Boston Collaborative Drug Surveillance Program, Boston University Medical Center, 1974, Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy, N. Engl. J. Med. 290: 15–19.CrossRefGoogle Scholar
  13. Bullock, J. L., Massey, F. M., and Gambrell, R. D., Jr., 1975, Use of medroxyprogesterone acetate to prevent menopausal symptoms, Obstet. Gynecol. 46: 165–168.PubMedGoogle Scholar
  14. Campbell, S., and Whitehead, M., 1977, Estrogen therapy and the postmenopausal syndrome, Clin. Obstet. Gynecol. 4: 31–47.Google Scholar
  15. Carmel, P. W., Araki, S., and Ferin, M., 1976, Pituitary stalk portal blood collection in rhesus monkeys: Evidence for pulsatile release of gonadotropin-releasing hormone (GnRH), Endocrinology 99: 243–248.PubMedCrossRefGoogle Scholar
  16. Casper, R. F., and Yen, S. S. C., 1981, Menopausal flushes: Effect of pituitary gonadotropin desensitization by a potent luteinizing hormone-releasing factor agonist, J. Clin. Endocrinol. Metabol. 53: 1056–1058.CrossRefGoogle Scholar
  17. Casper, R. F., Yen, S. S. C., and Wilkes, M. M., 1979, Menopausal flushes: A neuroendocrine link with pulsatile luteinizing hormone secretion, Science 205: 823–825.PubMedCrossRefGoogle Scholar
  18. Chakravarti, S., Collins, W. P., Forecast, J. D., Newton, J. R., Oram, D. H., and Studd, J. W. W., 1976, Hormonal profiles after the menopause, Brit. Med. J. 2: 784–787.PubMedCrossRefGoogle Scholar
  19. Clayden, J. R., Bell, J. W., and Pollard, P., 1974, Menopausal flushing: Double-blind trial of a non-hormonal medication, Brit. Med. J. 1: 409–412.PubMedCrossRefGoogle Scholar
  20. Collett, M. E., 1949, Basal metabolism at the menopause, J. Appi. Physiol. 1: 629–639.Google Scholar
  21. Coope, J., 1976, Double-blind cross-over study of estrogen replacement therapy, in: The Management of the Menopausal and Postmenopausal Years (S. Campbell, ed.), Baltimore University Park Press, Baltimore, pp. 159–168.Google Scholar
  22. Coope, J., and Patterson, J. S., 1978, A study of the effectiveness of propanolol in menopausal hot flushes, Brit. J. Obstet. Gynecol. 85: 472–475.CrossRefGoogle Scholar
  23. Coope, J., Thomson, J. M., and Poller, L., 1975, Effects of“natural oestrogen” replacement therapy on menopausal symptoms and blood clotting, Brit. Med. J. 4: 139–143.PubMedCrossRefGoogle Scholar
  24. Cooper, K. E., Cranston, W. I., and Snell, E. S., 1964, Temperature regulation during fever in man, Clin. Sci. 27: 345–356.PubMedGoogle Scholar
  25. Cox, B., and Lomax, P., 1977, Pharmacologic control of temperature regulation, Annu. Rev. Pharmacol. Toxicol. 17: 341–353.PubMedCrossRefGoogle Scholar
  26. Crowley, W. F., Jr., and McArthur, J. W., 1980, Simulation of the normal menstrual cycle in Kallman’s Syndrome by pulsatile administration of luteinizing hormone-releasing hormone (LHRH), J. Clin. Endocrinol. Metabol. 51: 173–175.CrossRefGoogle Scholar
  27. Crowley, W. R., O’Donohue, T. L., Wachslicht, H., and Jacobowitz, D. M., 1978, Effects of estrogen and progesterone on plasma gonadotropins and on catecholamine levels and turnover in discrete brain regions of ovariectomized rats, Brain Res. 154: 345–357.PubMedCrossRefGoogle Scholar
  28. DeFazio, J., Meldrum, D., Laufer, L., Vale, W., Rivier, J., Lu, J., and Judd, H., 1982, Induction of hot flashes in premenopausal women treated with a long acting GnRH agonist, Proc. 29th Annual Meeting Soc. Gynecol. Invest. (Abst. 142 ), Dallas, Texas, March 24–27.Google Scholar
  29. DeMorsier, G., and Gauthier, G., 1963, La dysplasie olfacto-genitale, Pathol. Biol. (Parrs) 11: 1267–1272.Google Scholar
  30. Dennerstein, L., Burrows, G. D., Hyman, G., and Wood, C., 1978, Menopausal hot flushes: A double-blind comparison of placebo, ethinyl oestradiol and norgestrel, Brit. J. Obstet. Gynecol. 85: 852–856.CrossRefGoogle Scholar
  31. Eik-Nes, K. B., 1964, On the relationship between testicular blood flow and secretion of testosterone in anesthetized dogs stimulated with human chorionic gonadotropins, Can. J. Physiol. Pharmacol. 42: 671–677.PubMedCrossRefGoogle Scholar
  32. Elkind-Hirsch, K. E., Ravnikar, V., Schiff, I., Tulchinsky, D., and Ryan, K. J., 1981, Determinations of endogenous immunoreactive LHRH levels in the plasma of postmenopausal women, Proc. 28th Annual Meeting Soc. Gynecol. Invest. (Abst. 20 ), St. Louis, Missouri, March 18–21.Google Scholar
  33. Erlik, Y., Meldrum, D. R., Lagasse, L. D., and Judd, H. L., 198la, Effect of megestrol acetate on flushing and bone metabolism in postmenopausal women, Maturitas 3: 167–172.Google Scholar
  34. Erlik, Y., Tataryn, I. V., Meldrum, D. R., Lomax, P., Bajorek, J. G., and Judd, H. L., 198 l b, Association of waking episodes with menopausal hot flushes, J. Am. Med. Assoc. 245: 1741–1744.Google Scholar
  35. Erlik, Y., Meldrum, D. R., and Judd, H. L., 1982, Estrogen levels in postmenopausal women with hot flashes, Obstet. Gynecol. 59: 403–407.PubMedGoogle Scholar
  36. Eskay, R. L., Mical, R. S., and Porter, J. C., 1977, Relationship between luteinizing hormone releasing hormone concentration in hypophysial blood and luteinizing hormone release in intact, castrated and electrochemically-stimulated rats, Endocrinology 100: 263–270.PubMedCrossRefGoogle Scholar
  37. Ferriman, D., and Purdie, A. W., 1965, Mechanism of menopausal hot flushes indicated by the effect of a dithiocarbamoylhydrazine, J. Endocrinology 31: 173–174.CrossRefGoogle Scholar
  38. Gambone, J., Meldrum, D., Laufer, L., Chang, J., Lu, J., and Judd, H., 1982a, Further delineation of hypothalamic dysfunction responsible for menopausal hot flashes, Proc. 29th Annual Meeting Soc. Gynecol. Invest. (Abst. 60 ), Dallas, Texas, March 24–27.Google Scholar
  39. Gambone, J. C., Pardridge, W. A., Lagasse, L. D., and Judd, H. L., 1982b, In vivo availability of circulating estradiol in postmenopausal women with and without endometrial cancer, Obstet. Gynecol. 59: 416–421.Google Scholar
  40. Greenfield, A. D., 1963, The circulation through the skin, Handbook Physiol. Sect. 2: 1325–1351.Google Scholar
  41. Hannan, J. H., 1927, The Flushings of the Menopause, Bailliere, Tindall and Cox, London, pp. 1–22.Google Scholar
  42. Houston, M., 1981, Clonidine hydrochloride: Review of pharmacologic and clinical aspects, Prog. Cardiovasc. Dis. 23 (5): 337–350.PubMedCrossRefGoogle Scholar
  43. Hunter, D. J. S., Julier, D., Franklin, M., and Green, E., 1977, Plasma levels of estrogen, luteinizing hormone, and follicle stimulating hormone following castration and estradiol implant, Obstet. Gynecol. 49: 180–185.PubMedGoogle Scholar
  44. Illner, P., Marques, P., Williams, D. D., Steiner, R. A., Green, W. L., Davis, S. L., Kendall, J. W., Johnson, D. G., and Gale, C. C., 1977, Endocrine responses to ruminai cooling in goats, in: Proceedings of the Third Symposium on the Pharmacology of Thermoregulation ( K. E. Cooper and P. Lomax, eds.), Karger, Basel, pp. 58–61.Google Scholar
  45. Jaszmann, L., Van Lith, N. D., and Zaat, J. C. A., 1969, The perimenopausal symptoms, Med. Gynecol. Soc. 4: 268–276.Google Scholar
  46. Judd, H. L., 1976, Hormonal dynamics associated with the menopause, Clin. Obstet. Gynecol. 19: 775–788.PubMedCrossRefGoogle Scholar
  47. Judd, H. L., Shamonki, I. M., Frumar, A. M., and Lagasse, L. D., 1982, Origin of serum estradiol in postmenopausal women, Obstet. Gynecol. 59: 680–686.PubMedGoogle Scholar
  48. Kales, A., Kales, J. D., Bixler, E. O., and Scharf, M. B., 1975, Effectiveness of hypnotic drugs with prolonged use: Flurozepan and pentobarbital, Clin. Pharmacol. Ther. 18: 356–363.PubMedGoogle Scholar
  49. King, J. R., Jr., 1926, Observations on the menopause I. The basal metabolism after the artifical menopause, Bull. Johns Hopkins Hosp. 39: 281–303.Google Scholar
  50. Kluger, M. J., 1978, The evolution and adaptive value of fever, Ann. Sci. 66: 38–43.Google Scholar
  51. Kobayashi, R. M., Lu, K. H., Moore, R. Y., and Yen, S. S. C., 1978, Regional distribution of hypothalamic luteinizing hormone-releasing hormone in proestrous rats: Effects of ovariectomy and estrogen replacement, Endocrinology 102: 98–105.PubMedCrossRefGoogle Scholar
  52. Krey, L. C., Butler, W. R., and Knobil, E., 1975, Surgical disconnection of the medial basal hypothalamus and pituitary function in the rhesus monkey. I. Gonadotropin secretion, Endocrinology 96: 1073–1087.PubMedCrossRefGoogle Scholar
  53. Larsen, I. F., 1977, Hot flashes after hypophysectomy, Brit. Med. J. 2: 1356.PubMedCrossRefGoogle Scholar
  54. Laufer, L. R., Erlik, Y., Meldrum, D. R., and Judd, H. L., 1982, Effect of clonidine on hot flashes in postmenopausal women, Obstet. Gynecol.,(in press).Google Scholar
  55. Leblanc, H., Lachelin, G. C. L., Abu-Fadil, S., and Yen, S. S. C., 1976, Effects of dopamine agonists on LH release in women, J. Clin. Endocrinol. Metabol. 44: 728–732.Google Scholar
  56. Lindsay, R., and Hart, D. M., 1978, Failure of responses of menopausal vasomotor symptoms to clonidine, Maturitas 1: 21–25.PubMedCrossRefGoogle Scholar
  57. Linton, E. A., Bennet, G. W., and Whitehead, S. A., 1979, Prostaglandins and the release of LHRH from hypothalamic synaptosomes, Neuroendocrinology 28: 394–401.PubMedCrossRefGoogle Scholar
  58. Lomax, P., and Knox, G. V., 1973, The sites and mechanisms of action of drugs affecting thermoregulation, in: The Pharmacology of Thermoregulation, Karger, Basel, pp. 146–154.Google Scholar
  59. Mashchak, C. A., Kletzky, O. A., Artel, R., and Mishell, D. R., Jr., 1982, Postmenopausal vasomotor perfusion changes investigated by digital plethysmography and plasma catecholamine levels, Proc. 29th Annual Meeting Soc. Gynecol. Invest. (Abst. 277 ), Dallas, Texas, March 24–27.Google Scholar
  60. McKinlay, S., and Jeffreys, M., 1974, The menopausal syndrome, Brit. J. Prey. Soc. Med. 28: 108–115.Google Scholar
  61. Meldrum, D. R., Shamonki, I. M., Frumar, A. M., Tataryn, I. V., Chang, R. J., and Judd, H. L., 1979, Elevations in skin temperature of the finger as an objective index of postmenopausal hot flashes: Standardization of the techniques, Am. J. Obstet. Gynecol. 135: 713–717.PubMedGoogle Scholar
  62. Meldrum, D. R., Tataryn, I. V., Frumar, A. M., Erlik, Y., Lu, K. H., and Judd, H. L., 1980, Gonadotropins, estrogens, and adrenal steroids during the menopausal hot flash, J. Clin. Endocrinol. Metabol. 50: 685–689.CrossRefGoogle Scholar
  63. Meldrum, D. R., Erlik, Y., Lu, J. H. K., and Judd, H. L., 1981, Objectively recorded hot flashes in patients with pituitary insufficiency, J. Clin. Endocrinol. Metabol. 52: 684–687.CrossRefGoogle Scholar
  64. Molnar, G. W., 1975, Body temperatures during menopausal hot flashes, J. Appi. Physiol. 38: 499–503.Google Scholar
  65. Molnar, G. W., 1979, Investigation of hot flashes by ambulatory monitoring, Am. J. Physiol. 237: R306–310.PubMedGoogle Scholar
  66. Mulley, G., and Mitchell, J. R. A., 1976, Menopausal flushing: Does oestrogen therapy make sense, Lancet 1: 1397–1399.PubMedCrossRefGoogle Scholar
  67. Mulley, G., Mitchell, J. R. A., and Tattersall, R. B., 1977, Hot flushes after hypophysectomy, Brit. Med. J. 2: 1062.PubMedCrossRefGoogle Scholar
  68. Neugarten, B. L., and Kraines, R. J., 1965, Menopausal symptoms in women of various ages, Psychosom. Med. 27: 266–273.PubMedGoogle Scholar
  69. Pang, C. N., Zimmermann, E., and Sawyer, C. H., 1977, Morphine inhibition of the preovulatory surges of plasma luteinizing hormone and follicle stimulating hormone in the rat, Endocrinology 101: 1726–1732.PubMedCrossRefGoogle Scholar
  70. Pardridge, W. M., and Mietus, L. J., 1979, Transport of steroid hormones through the rat blood-brain barrier: Primary role of albumin-bound hormone, J. Clin. Invest. 64: 145–154.PubMedCrossRefGoogle Scholar
  71. Pfeffer, R. I., and Van den Noort, S., 1976, Estrogen use and stroke risk in postmenopausal women, Am. J. Epidemiol. 103: 445–456.PubMedGoogle Scholar
  72. Plant, T. M., Krey, L. C., Moossy, J., McCormack, J. T., Hess, D. L., and Knobil, E., 1978, The arcuate nucleus and the control of gonadotropin and prolactin secretion in the female rhesus monkey, Endocrinology 102: 52–62.PubMedCrossRefGoogle Scholar
  73. Porter, J. C., and Klaiber, M. S., 1965, Corticosterone secretion in rats as a function of ACTH input and adrenal blood flow, Am. J. Physiol. 209: 811–814.PubMedGoogle Scholar
  74. Quigley, M. E., Sheehan, K. L., Casper, R. F., and Yen, S. S. C., 1980, Evidence for increased dopaminergic and opioid activity in patients with hypothalamic hypogonadotropic amenorrhea, J. Clin. Endocrinol. Metabol. 50: 949–954.CrossRefGoogle Scholar
  75. Reaves, T. A., and Hayward, J. M., 1979, Hypothalamic and extrahypothalamic thermoregulatory centers, in: Body Temperature: Regulation, Drug Effects and Therapeutic Implications (P. Lomax and E. Schonbaum, eds.), Dekker, New York, pp. 39–70.Google Scholar
  76. Reynolds, S. R. M., 1941, Dermovascular action of estrogen, the ovarian follicular hormone, J. Invest. Dermatol. 4: 7–22.CrossRefGoogle Scholar
  77. Reynolds, W. W., Casterlin, M. E., and Covert, J. B., 1974, Behavioral fever in teleost fishes, Nature 259: 41–42.CrossRefGoogle Scholar
  78. Satinoff, E., and Cantor, A., 1975, Intraventricular norepinephrine and thermoregulation in rats, in: Temperature Regulation and Drug Action (P. Lomax, E. Schonbaum, and J. Jacob, eds.), Karger, Basel, pp. 103–110.Google Scholar
  79. Schiff, I., Regestein, Q., Tulchinsky, D., and Ryan, K. J., 1979, Effects of estrogens on sleep and psychological state of hypogonadal women, J. Am. Med. Assoc. 242: 2405–2407.CrossRefGoogle Scholar
  80. Siiteri, P. K., and MacDonald, P. C., 1973, Role of extraglandular estrogen in human endocrinology, in: Handbook of Physiology: Endocrinology, Vol. 2(1), ( R. O. Greep and E. Astwood, eds.), American Physiological Society, Washington, D.C., pp. 615–629.Google Scholar
  81. Simpkins, J. W., and Kalra, S. P., 1979, Central site(s) of norepinephrine and LHRH interaction, Fed. Proc. 38: 1107.Google Scholar
  82. Snell, E. S., and Atkins, E., 1968, The Mechanisms of Fever, the Biological Basis of Medicine (E. E. Bittar and N. Bittar, eds.), Academic Press, New York, pp. 397–419.Google Scholar
  83. Stern, M. P., Brown, B. W., Haskell, W. L., Farquhar, J. W., Wehrle, C. L., and Wood, P. D. S., 1976, Cardiovascular risk and use of estrogens or estrogen-progestagen combinations, J. Am. Med. Assoc. 235: 811–815.CrossRefGoogle Scholar
  84. Stone, S. C., Mickal, A., and Rye, P. H., 1975, Postmenopausal symptomatology, maturation index, and plasma estrogen levels, Obstet. Gynecol. 45: 625–627.PubMedCrossRefGoogle Scholar
  85. Sturdee, D. W., and Reece, B. L., 1979, Thermography of menopausal hot flushes, Maturitas 1: 201–205.PubMedCrossRefGoogle Scholar
  86. Sturdee, D. W., Wilson, K. A., Pipili, E., and Crocker, A. D., 1978, Physiological aspects of menopausal hot flush, Brit. Med. J. 2: 79–80.PubMedCrossRefGoogle Scholar
  87. Tataryn, I. V., Meldrum, D. R., Lu, K. H., Frumar, A. M., and Judd, H. L., 1979, LH, FSH, and skin temperature during the menopausal hot flash, J. Clin. Endocrinol. Metabol. 49: 152–154.CrossRefGoogle Scholar
  88. Tataryn, I. V., Lomax, P., Bajorek, J. G., Chesarek, W., Meldrum, D. R., and Judd, H. L., 1980, Postmenopausal hot flushes: A disorder of thermoregulation, Maturitas 2: 101–107.PubMedCrossRefGoogle Scholar
  89. Tataryn, I. V., Lomax, P., Meldrum, D. R., Bajorek, J. G., Chesarek, W., and Judd, H. L., 1981, Objective techniques for the assessment of postmenopausal hot flashes, Obstet. Gynecol. 57: 340–344.PubMedGoogle Scholar
  90. Thompson, J., and Oswald, I., 1977, Effect of estrogen on the sleep, mood and anxiety of menopausal women, Brit. Med. J. 2: 1317–1319.CrossRefGoogle Scholar
  91. Thompson, B., Hart, S. A., and Durno, D., 1973, Menopausal age and symptomatology in general practice, J. Biol. Sci. 5: 71–82.Google Scholar
  92. Utian, W. H., 1972, The mental tonic effect of oestrogens administered to oophorectomized females, S. Afr. Med. J. 46: 1079–1082.PubMedGoogle Scholar
  93. Venables, R., 1967, Methods in psychophysiology (C. C. Brown, ed.), Williams Wilkins, Baltimore, pp. 1–26.Google Scholar
  94. Yen, S. S. C., Rebar, R., Vandenberg, G., and Judd, H., 1973, Hypothalamic amenorrhea and hypogonadotropinism: Responses to synthetic LRF, J. Clin. Endocrinol. Metabol. 36: 811–816.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Howard L. Judd
    • 1
  1. 1.Department of Obstetrics and GynecologyUniversity of California at Los Angeles School of MedicineLos AngelesUSA

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