A Comparative Analysis of the Effects of Narcotics, Alcohol and the Barbiturates on the Hypothalamic-Pituitary-Gonadal Axis

  • Theodore J. Cicero
  • Thomas M. Badger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 85B)


The purpose of this paper is to provide an overview of our current state of knowledge regarding the effects of alcohol, the narcotics and the barbiturates on the hypothalamic-pituitary-gonadal axis in the male. Three facets of this problem will be considered: acute drug effects; chronic effects, particularly with respect to the development of tolerance and physical dependence; and, finally, an attempt will be made to indicate the way in which these three substances of abuse are similar and/or dissimilar in their effects on this system. The effects of acute and chronic treatment with narcotics, alcohol and the barbiturates will be discussed first and then an attempt will be made, in a General Discussion, to summarize the data, make general comparisons between the drugs and suggest future lines of research.


Luteinizing Hormone Testosterone Level Serum Testosterone Serum Testosterone Level Luteinizing Hormone Level 
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. Azizi, F., Vagenakis, A.G., Longcope, C., Ingbar, S.H. and Braverman, L.E.: Decreased serum testosterone concentration in male heroin and methadone addicts. Steroids 22:467–472, 1973.CrossRefGoogle Scholar
  2. Badr, S.M. and Bartke, A.: Effect of ethyl alcohol on plasma testosterone levels in mice. Steroids 23:921–927, 1974.CrossRefGoogle Scholar
  3. Beattie, C.W., Campbell, C.S., Nequin, L.G., Soyha, L.F. and Schwartz, N.B.: Barbiturate blockade of tonic LH secretion in the male and female rat. Endocrinology 92:1630–1638, 1973.CrossRefGoogle Scholar
  4. Cicero, T.J. and Meyer, E.R.: Morphine pellet implantation in rats: Quantitative assessment of tolerance and dependence. J. Pharmacol. Exp. Ther. 184:404–408, 1973.Google Scholar
  5. Cicero, T.J., Meyer, E.R., Bell, R.D. and Wiest, W.: Effects of morphine on the secondary sex organs and plasma testosterone levels of rats. Res. Commun. Chem. Pathol. Pharmacol. 7: 17–24, 1974.Google Scholar
  6. Cicero, T.J., Bell, R.D., Wiest, W.G., Allison, J.H., Polakoski, K. and Robins, E.: Function of the male sex organs in heroin and methadone users. N. Engl. J. Med. 292:882–887, 1975a.CrossRefGoogle Scholar
  7. Cicero, T.J., Meyer, E.R., Wiest, W.G., Olney, J.W. and Bell, R.D.: Effects of chronic morphine administration on the reproductive system of the male rat. J. Pharmacol. Exp. Ther. 192:542–548, 1975b.Google Scholar
  8. Cicero, T.J., Meyer, E.R., Bell, R.D. and Koch, G.A.: Effects of morphine and methadone on testosterone, luteinizing hormone and the secondary sex organs of the male rat. Endocrinology 98: 365–370, 1976a.CrossRefGoogle Scholar
  9. Cicero, T.J., Wilcox, C.E., Bell, R.D. and Meyer, E.R.: Acute reductions in serum testosterone levels by narcotics in the male rat: stereospecificity, blockade by naloxone and tolerance. J. Pharmacol. Exp. Ther. 198:340–346, 1976b.Google Scholar
  10. Cicero, T.J., Bell, R.D., Meyer, E.R. and Schweitzer, J.: Narcotics and the hypothalamic-pituitary-gonadal axis: acute effects on luteinizing hormone, testosterone and androgen dependent systems. J. Pharmacol. Exp. Ther. 1976c, in press.Google Scholar
  11. Fahim, M.S., Dement, G., Hall, D.G. and Fahim, Z.: Induced alterations in hepatic metabolism of androgens in the rat. Amer. J. Obstet. Gynec. 107:1085–1091, 1970.Google Scholar
  12. Freund, G.: Alcohol withdrawal syndrome in mice. Arch. Neurol. 21:315–320, 1969.CrossRefGoogle Scholar
  13. Freund, G., and Walker, D.W.: Sound-induced seizures during ethanol withdrawal in mice. Psychopharmacologia 22:45–59, 1971.CrossRefGoogle Scholar
  14. Galvao-Teles, A., Anderson, D.C., Burke, C.W., Marshall, J.C., Corker, C.S., Brown, R.L. and Clark, M.L.: Biologically active androgens and estradiol in men with chronic liver disease. Lancet 1:173–177, 1973.CrossRefGoogle Scholar
  15. Gordon, G.G., Olivo, J., Rafii, F., and Southren, A.L.: Conversion of androgens to estrogens in cirrhosis of the liver. J. Clin. Endocrinol. Metab. 40:1018–1026, 1975.CrossRefGoogle Scholar
  16. Hunter, B.E., Walker, D.W., Boast, C.A. and Zornetzer, S.F.: Ethanol dependence in the rat. Neural and Behavioral correlates. Pharmacol. Biochem. Behav. 1:719–725, 1973.CrossRefGoogle Scholar
  17. Kosterlitz, H.W. and Waterfield, A.A.: In vitro models in the study of structure-activity relationships of narcotic analgesics. Ann. Rev. Pharmacol. 15:29–57, 1975.CrossRefGoogle Scholar
  18. Lloyd, C.W. and Williams, R.H.: Endocrine changes associated with Laennec’s cirrhosis of the liver. Amer. J. Med. 4:315–330, 1948.CrossRefGoogle Scholar
  19. Martin, W.R., Jasinski, D.R., Haertzen, C.A., Kay, P.C., Jones, B.E., Mansky, P.A. and Carpenter, R.W.: Methadone- a reevaluation. Arch. Gen. Psychiat. 28:286–295, 1973.CrossRefGoogle Scholar
  20. McCormack, C.E. and Strauss, W.F.: Reversal by Progesterone of phenobarbitone-blockade of ovulation in the prepubertal rat primed with pregnant mouse serum gonadotropin. J. Endocr. 65: 177–182, 1975.CrossRefGoogle Scholar
  21. Mendelson, J.H. and Mello, N.K.: Alcohol, aggression and androgens. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 52:225–247, 1974.Google Scholar
  22. Mendelson, J.H., Mendelson, J.E. and Patch, V.D.: Plasma testosterone levels in heroin addiction and during methadone maintenance. J. Pharmacol. Exp. Ther. 192:211–217, 1975a.Google Scholar
  23. Mendelson, J.H., Meyer, R.E., Ellingboe, J., Mirin, S.M. and McDougle, M.: Effects of heroin and methadone on plasma Cortisol and testosterone. J. Pharmacol. Exp. Ther. 195:296–302, 1975b.Google Scholar
  24. Mendelson, J.H., Inturrisi, C.E., Renault, P. and Senay, E.C.: Effects of acetylmethadol on plasma testosterone. Clinical Pharmacol. Ther. 19:371–374, 1976.Google Scholar
  25. Meyer, R.R., Karavolas, H.J., Klausing, M. and Norgard, P.W.: Blood progesterone and pregnenolone levels during phenobarbital (PB) block of PMS-induced ovulation in immature rats. Endocrinology 88:983–990, 1971.CrossRefGoogle Scholar
  26. Moyle, W.R. and Ramachandran, J.: Effect of LH on steroidogenesis and cyclic AMP accumulation in rat Leydig cell preparations and mouse tumor Leydig cells. Endocrinology 93:127–134, 1973.CrossRefGoogle Scholar
  27. Niswender, G.P., Reichert, L.E., Midgley, A.R. and Nalbandov, A.V.: Radioimmunoassay for bovine and ovine luteinizing hormone. Endocrinology 84:1166–1173, 1969.CrossRefGoogle Scholar
  28. Pert, C.B. and Snyder, S.H.: Properties of opiate receptor binding, in brain. P.N.A.S. USA 70:2243–2247, 1973.CrossRefGoogle Scholar
  29. Rubin, E., Lieber, CS., Altman, K., Gordon, C.G. and Southren, A.L.: Prolonged ethanol consumption increases testosterone metabolism in the liver. Science 191:563–564, 1976.CrossRefGoogle Scholar
  30. Shin, S.H. and Jowitt, C.: Effects of castration on luteinizing hormone and luteinizing hormone releasing factor in the male rat. J. Endocrin. 65:447–448, 1975.CrossRefGoogle Scholar
  31. Sorrentino, S.: Ovulation in PMS-treated rats with gonadotropin releasing hormone after pentobarbital and melatonin block. Neuroendocrinology 19:170–176, 1975.CrossRefGoogle Scholar
  32. Southren, A.L., Gordon, G.G., Olivo, J., Rafii, F., and Rosenthal, W.S.: Androgen metabolism in cirrhosis of the liver. Metabolism 22:695–702, 1973.CrossRefGoogle Scholar
  33. Symons, A.M. and Marks, V.: Effects of alcohol on weight gain and the hypothalamic-pituitary-gonadotropin axis in the maturing male rat. Biochem. Pharmacol. 24:955–958, 1975.CrossRefGoogle Scholar
  34. Thomas, J.A. and Dombrosky, J.T.: Effects of methadone on the male reproductive system. Arch. Int. Pharmacodyn. Ther. 215:215–221, 1975.Google Scholar
  35. Van Thiel, D.H., Lester, R. and Sherins, R.J.: Hypogonadism in alcoholic liver disease: Evidence for a double effect. Gastroenterology 61:1188–1199, 1974.Google Scholar
  36. Van Thiel, D.H., Gavaler, J.S., Lester, R., and Goodman, M.D.: Alcohol-induced testicular atrophy. An experimental model for hypogonadism occurring in chronic alcoholic men. Gastroenterology 69: 326–332, 1975.Google Scholar
  37. Wallgren, H., and Barry, H.: Actions of Alcohol Vol. I, Chapters 4, 5,6 and 7. Elsevier Publishing Company, New York, pp. 156–387, 1970.Google Scholar
  38. Yamamoto, M., Diebel, N.D. and Bogdanove, E.M.: Analysis of initial and delayed effects of orchidectomy and ovariectomy on pituitary and serum LH levels in adult and immature rats. Endocrinology 86:1102–1111, 1970.CrossRefGoogle Scholar
  39. Ylikahri, R., Huttunen, M., Harkonen, M., Seuderling, U., Onikki, S., Karonen, S.L. and Adlercreutz, H.: Low plasma testosterone values in men during hangover. J. Steroid Biochem. 5:655–658, 1974.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Theodore J. Cicero
    • 1
  • Thomas M. Badger
    • 1
  1. 1.Department of PsychiatryWashington University School of MedicineSt. LouisUSA

Personalised recommendations