Endogenous opioid peptides and the control of the menstrual cycle

Eur J Obstet Gynecol Reprod Biol. 1984 Dec;18(5-6):365-73. doi: 10.1016/0028-2243(84)90059-5.


This paper reviews recent experimental evidence which supports a role for endogenous opioid peptides in the control of gonadotropin function. In primates, cell bodies containing endogenous opioid peptides have been located within the hypothalamus in areas rich in gonadotropin-releasing hormone (GnRH) and dopamine. The release of beta-endorphin from these hypothalamic neurons is influenced by gonadal steroids, maximal release being observed when both estradiol and progesterone are present. beta-Endorphin has been shown to decrease LH secretion, and naloxone, an opiate antagonist, reverses this action. The LH-releasing activity of naloxone parallels variations in hypothalamic beta-endorphin secretory activity, so that maximal effects are seen during the luteal phase of the cycle. Present evidence indicates that opiates exert their effect on LH via a hypothalamic site. It is concluded that increased opioid inhibition of the GnRH-LH axis is responsible for the decline in LH pulse frequency during the luteal phase. The studies provide evidence for a chemical basis rationalizing relationships between reproductive function and stress, and have further implication on other forms of amenorrhea.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amenorrhea / blood
  • Amenorrhea / etiology
  • Animals
  • Arcuate Nucleus of Hypothalamus / analysis
  • Brain Chemistry
  • Corticotropin-Releasing Hormone / metabolism
  • Endorphins / analysis
  • Endorphins / physiology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Follicle Stimulating Hormone / metabolism
  • Haplorhini
  • Humans
  • Hypothalamus, Middle / analysis
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / metabolism
  • Menstrual Cycle*
  • Naloxone / pharmacology
  • Pituitary Hormone-Releasing Hormones / metabolism
  • Pro-Opiomelanocortin / biosynthesis
  • Prolactin / blood
  • Stress, Psychological / physiopathology
  • beta-Endorphin


  • Endorphins
  • Pituitary Hormone-Releasing Hormones
  • Naloxone
  • beta-Endorphin
  • Pro-Opiomelanocortin
  • Prolactin
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Corticotropin-Releasing Hormone