Possible Roles of Melatonin in Disturbances of the Menstrual Cycle

  • A. Brzezinski
Conference paper


Until a few decades ago textbooks of physiology or endocrinology routinely dismissed the pineal gland as Decartes’ “seat of the soul,” or as a calcified vestige of a more phylogenetically primitive third eye whose only function, in humans, was as a landmark for neuroradiologists. However, since the end of the 1950s rapid and continuing progress has been made in uncovering functions for the pineal gland and for its principal secretion, melatonin (Wurtman and Moskovitz 1977). The importance of this hormone in controlling mammalian reproduction, especially among seasonal breeders, now appears to be well established (Wurtman et al. 1963; Reiter 1980). Recently, evidence has been published suggesting that the pineal, acting via melatonin, may also be involved in the regulation of human reproductive processes, particularly involving puberty (Waldhauser et al. 1984) and the menstrual cycle (Webley and Leidenberger 1986; Brzezinski et al. 1988). The actions of each of these processes and evidence implicating melatonin in certain disturbances of the menstrual cycle are discussed below.


Menstrual Cycle Pineal Gland Melatonin Level Melatonin Secretion Luteinizing Hormone Secretion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anton-Tay F, Chou C, Anton S, Wurtman RJ (1968) Brain serotonin concentrations: elevation following intraperitoneal administration of melatonin. Science 162: 277–278PubMedCrossRefGoogle Scholar
  2. Arendt J (1979) Radioimmunoassayable melatonin: circulating patterns in men and sheep. Prog Brain Res 52: 249–258PubMedCrossRefGoogle Scholar
  3. Beitins IZ, Barkan A, Klibaski A, Kyung N, Reppert SM, Badger TM, McArthur JW (1985) Hormonal responses to short-term fasting in postmenopausal women. J Clin Endocrinol Metab 60: 1120–1124PubMedCrossRefGoogle Scholar
  4. Berga SL, Mortola JF, Yen SSC (1988) Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 66: 242–244PubMedCrossRefGoogle Scholar
  5. Birau N (1981) Melatonin in human serum: progress in screening investigation and clinic. In: Birau N (ed) Melatonin: current status and perspectives. Pergamon, Oxford, pp 297–326Google Scholar
  6. Bittman EL (1984) Melatonin and photoperiodic time measurement: evidence from rodents and ruminants. In: Reiter RJ (ed) The pineal gland. Raven, New York, pp 155–192Google Scholar
  7. Bittman EL, Karsch FJ (1984) Nightly duration of pineal melatonin secretion determines the response to day length in the ewe. Biol Reprod 30: 585–590PubMedCrossRefGoogle Scholar
  8. Bittman EL, Kaynard AH, Olster DH, Robinson JE, Yellon SM, Karsch FJ (1985) Pineal melatonin mediates photoperiod control of pulsatile luteinizing hormone secretion in the ewe. Neuroendocrinology 40: 409–418PubMedCrossRefGoogle Scholar
  9. Brzezinski A, Seibel MM, Lynch HJ, Deng HM, Wurtman RJ (1987) Melatonin in human preovulatory follicular fluid. J Clin Endocrinol Metab 64: 865–867PubMedCrossRefGoogle Scholar
  10. Brzezinski A, Lynch HJ, Seibel MM, Deng MH, Wurtman RJ (1988) The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women. J Clin Endocrinol Metab 66: 891–895PubMedCrossRefGoogle Scholar
  11. Carr DB, Reppert SM, Bullen B, Skrinar G, Beitins IZ, Arnold M, Rossenblat M, McArthur JW (1981) Plasma melatonin increases during exercise in women. J Clin Endocrinol Metab 53: 224–226PubMedGoogle Scholar
  12. Carter DS, Hall VD, Tamarkin L, Goldman BD (1982) Pineal is required for testicular maintenance in the Turkish hamster. Endocrinology 111: 863–871PubMedCrossRefGoogle Scholar
  13. Chu EW, Wurtman RJ, Axelrod J (1964) An inhibitory effect of melatonin on the estrus phase of the estrus cycle of the rodent. Endocrinology 75: 238–242PubMedCrossRefGoogle Scholar
  14. Cohen M, Roselle D, Chabner B (1978) Evidence for a cytoplasmic melatonin receptor. Nature 274: 894–895PubMedCrossRefGoogle Scholar
  15. Dewan EM, Menkin MF, Rock J (1978) Effect of photic stimulation on the human menstrual cycle. Photochem Photobiol 27: 581–585PubMedCrossRefGoogle Scholar
  16. Ehara Y, Siler T, VandenBerg G, Sinha YN, Yen SSC (1973) Circulating prolactin levels during the menstrual cycle: episodic release and diurnal variation. Am J Obstet Gynecol 117: 962–970PubMedGoogle Scholar
  17. Fellenberg AJ, Phillipou G, Seamark F (1982) Urinary 6-sulphatoxy melatonin excretion during the human menstrual cycle. Clin Endocrinol 17: 71–75CrossRefGoogle Scholar
  18. Fraschini F, Mess B, Martini L (1968a) Pineal gland, melatonin and control of luteinizing hormone secretion. Endocrinology 82: 919–924PubMedCrossRefGoogle Scholar
  19. Fraschini F, Mess B, Piva F, Martini L (1968b) Brain receptors sensitive to indole compounds: function in control of luteinizing hormone secretion. Science 159: 1104–1105PubMedCrossRefGoogle Scholar
  20. Hariharasubramanian N, Nair NPV, Pilapil C (1984) Orcadian rhythm of plasma melatonin and Cortisol during the menstrual cycle. In: Brown GM, Wainwright SD (eds) The pineal gland endocrine aspects. Pergamon, Toronto, pp 31–35Google Scholar
  21. Heubner O (1898) Tumor der glandula pinealis. Dtsch Med Wochenschr 24 (2): 215Google Scholar
  22. Hoffmann K (1973) The influence of photoperiod and melatonin on testis size and body weight in the Djungarian hamster. J Comp Physiol 85: 267–282CrossRefGoogle Scholar
  23. Kitay JI (1954) Pineal lesions and precocious puberty: a review. J Clin Endocrinol Metab 54: 1056–1058Google Scholar
  24. Kitay JI, Altschule MD (1954) The pineal gland. A review of the physiologic literature. Harvard University Press, CambridgeGoogle Scholar
  25. Lang U, Aubert ML, Conne BS, Bradtke JC, Sizonenko PC (1983) Influence of exogenous melatonin on melatonin secretion and on the neuroendocrine reproductive axis of intact male rats during sexual maturation. Endocrinology 112: 1578–1584PubMedCrossRefGoogle Scholar
  26. Lang U, Rivest RW, Schlaepfer LV, Aubert ML, Sizonenko PC (1984) Diurnal rhythm of melatonin action an sexual maturation of the male rat. Neuroendocrinology 38: 261–268PubMedCrossRefGoogle Scholar
  27. Lemaitre BJ, Bouillie J, Hartmann L (1981) Variation in human melatonin excretion during the first 30 years of life. Clin Chim Acta 110: 77–82PubMedCrossRefGoogle Scholar
  28. Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP (1980) Light suppresses melatonin secretton in humans. Science 210: 1267–1269PubMedCrossRefGoogle Scholar
  29. Lieberman HR, Waldhauser F, Garfield G, Wurtman RJ (1984) The effects of melatonin on human mood and performance. Brain Res 323: 201–207PubMedCrossRefGoogle Scholar
  30. Lynch HJ, Wurtman RJ, Moskowitz MA (1975) Daily rhythm in human urinary melatonin. Science 187: 169–171PubMedCrossRefGoogle Scholar
  31. Macphee AA, Cole FE, BF Rice (1974) The effect of melatonin on steroidogenesis by the human ovary in vitro. J Clin Endocrinol Metab 40: 688–696CrossRefGoogle Scholar
  32. Martin JE, Sattler C (1982) Selectivity of melatonin pituitary inhibition for luteinizing hormone-releasing hormone. Neuroendocrinology 34: 112–116PubMedCrossRefGoogle Scholar
  33. Martin JE, Engel J, Klein DC (1977) Inhibition of the in vitro pituitary response to luteinizing hormone-releasing hormone by melatonin, serotonin and 5-methoxytryptamine. Endocrinology 100: 675–680PubMedCrossRefGoogle Scholar
  34. Martin JE, McKellar S, Klein DC (1980) Melatonin inhibition of the in vivo pituitary response to luteinizing hormone-releasing hormone in the neonatal rat. Neuroendocrinology 31: 13–17PubMedCrossRefGoogle Scholar
  35. Molodykh AS (1976) Melatonin blood levels and urinary excretion change through the menstrual cycle. Actual’nye voprosy akusherstva i gynecologii. Moskva Meditsina, Moskva, pp 84–85Google Scholar
  36. Ozaki Y, Wurtman RJ, Alonso R, Lynch HJ (1978) Melatonin secretion decreases during the proestrus stage of the rat estrus cycle. Proc Natl Acad Sci USA 75: 531–534PubMedCrossRefGoogle Scholar
  37. Pelham RW, Vaughan GM, Sandock KL, Vaughan MK (1973) 24 hour cycle of a melatonin-like substance in the plasma of human males. J Clin Endocrinol Metab 37:341–344CrossRefGoogle Scholar
  38. Quay WB (1963) Circadian rhythms in rat pineal serotonin and its modification by estrus cycle and photoperiod. Gen Comp Endocrinol 3: 473–479CrossRefGoogle Scholar
  39. Reiter RJ (1972) Evidence for the refractoriness of the pituitary-gonadal axis to the pineal gland in golden hamsters and its possible implications in annual reproductive rhythms. Anat Rec 173: 365–372PubMedCrossRefGoogle Scholar
  40. Reiter RJ (1980) The pineal and its hormones in the control of reproduction in mammals. Endocrinol Rev 1: 109–131CrossRefGoogle Scholar
  41. Reiter RJ, Hester RJ (1966) Interrelationship of the pineal gland, and the superior cervical ganglia and the photoperiod in the regulation of the endocrine systems of hamsters. Endocrinology 79: 1168–1170PubMedCrossRefGoogle Scholar
  42. Ronkainen H, Pakarinen A, Kirkinen P, Kauppila A (1985) Physical exercise-induced changes and season associated differences in pituitary-ovarian function of runners and joggers. J Clin Endocrinol Metab 60: 416–419PubMedCrossRefGoogle Scholar
  43. Sandahl B (1978) Seasonal birth pattern in Sweden in relation to birth order and maternal age. Acta Obstet Gynecol Scand 57: 393–396PubMedCrossRefGoogle Scholar
  44. Seibel MM, Shine W, Smith DM, Taymor ML (1982) Biological rhythm of the luteinizing hormone surge in women. Fertil Steril 37: 708–711Google Scholar
  45. Stetson MH, Matt KS, Watson-Whitmyre M (1976) Photoperiodism and reproduction in Golden hamsters: circadian organization and the termination of photorefractoriness. Biol Reprod 14: 531–537PubMedCrossRefGoogle Scholar
  46. Tamarkin L, Westrom WK, Hamill AI, Goldman BD (1976) Effect of melatonin on reproductive system of male and female Syrian hamsters. Endocrinology 99: 1534–1541PubMedCrossRefGoogle Scholar
  47. Testart J, Frydman R, Roger M (1982) Seasonal influence of diurnal rhythms in the onset of the plasma LH surge in women. J Clin Endocrinol Metab 55: 374–377PubMedCrossRefGoogle Scholar
  48. Timonen S, Carpen E (1968) Multiple pregnancies and photoperiodicity. Ann Chir Gynaec Fenn 57: 135–138PubMedGoogle Scholar
  49. Timonen S, Franzas B, Wichman K (1964) Photosensitivity of the human pituitary. Ann Chir Gynaecol Fenn 53: 165–169PubMedGoogle Scholar
  50. Vaughan GM, Allen JP, Tullis W, Siler-Khodr TM, Pena A, Sackman W (1978a) Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men. J Clin Endocrinol Metab 47: 566–571PubMedCrossRefGoogle Scholar
  51. Vaughan MK, Little JC, Johnson LY, Blask DE, Vaughan GM, Reiter RJ (1978b) Effects of melatonin and analogues of arginine vasotocin on plasma prolactin levels in adult male rats. Horm Res 9: 236–242PubMedCrossRefGoogle Scholar
  52. Waldhauser F, Weissenbacher G, Zeitlhuber U, Waldhauser M, Wurtman RJ (1984) Fall in nocturnal serum melatonin levels during prepuberty and pubescence. Lancet 1: 362–365PubMedCrossRefGoogle Scholar
  53. Waldhauser F, Lieberman HR, Lynch HJ, Waldhauser M, Herkner K, Frisch H, Wurtman RJ, Crowley WF (1987) A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or Cortisol. Neuroendocrinology (in press)Google Scholar
  54. Walker RF, McCamant S, Timiras PS (1982) Melatonin and the influence of the pineal gland on timing of the LH surge in rats. Neuroendocrinology 35: 37–42PubMedCrossRefGoogle Scholar
  55. Webley GE, Leidenberger F (1986) The circadian pattern of melatonin and its positive relationship with progesterone in women. J Clin Endocrinol Metab 63: 323PubMedCrossRefGoogle Scholar
  56. Webley GE, Lenton EA (1987) The temporal relationship between melatonin and prolactin in women. Fertil Steril 48: 218–222PubMedGoogle Scholar
  57. Webley GE, Luck MR (1985) Melatonin directly stimulates the secretion of progesterone by human granulosa cells. Acta Endocrinol [Suppl] (Copenh) 108: 91–92Google Scholar
  58. Wetterberg L (1979) Clinical importance of melatonin. Prog Brain Res 52: 539–547PubMedCrossRefGoogle Scholar
  59. Wetterberg L, Arendt J, Paunier L, Sizonenko PC, Van Donselaar W, Heyden T (1976) Human serum melatonin changes during the menstrual cycle. J Clin Endocrinol Metab 42: 185–188PubMedCrossRefGoogle Scholar
  60. Wurtman RJ, Moskowitz MA (1977) The pineal organ. N Engl J Med 296:1329–1333, 1383–1386PubMedCrossRefGoogle Scholar
  61. Wurtman RJ, Waldhauser F (1986) Melatonin in humans. J Neural TransmGoogle Scholar
  62. Wurtman RJ, Axelrod J, Chu EW (1963) Melatonin, a pineal substance: its effect on the rat ovary. Science 141: 277–278PubMedCrossRefGoogle Scholar
  63. Wurtman RJ, Axelrod J, Potter LT (1964) The uptake of H3-melatonin in endocrine and nervous tissues and the effects of constant light exposure. J Pharmacol Exp Ther 143: 314–318PubMedGoogle Scholar
  64. Ying SY, Greep RO (1973) Inhibition of ovulation by melatonin by the cyclic rat. Endocrinology 92: 333–335PubMedCrossRefGoogle Scholar
  65. Zispal N, Egosi Y, Laudon M (1982) Inhibition of dopamine release by melatonin: regional distribution in the rat brain. Brain Res 246: 161–164CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • A. Brzezinski
    • 1
  1. 1.Department of Obstetrics and GynecologyHadassah University HospitalJerusalemIsrael

Personalised recommendations