Steroid Ulcers

  • Z. Sandor
  • S. Szabo
Conference paper


“Steroid ulcer” is an unfortunate misnomer and clinical jargon because it implies a not clearly established relationship between steroids and ulcer. Neither of the words are actually being used very precisely: namely, steroid in this context usually means glucocorticoid while neglecting the modern classification of steroids (see below) and ulcer is not a precise definition either, because most of these lesions are actually superficial mucosal erosions and they rarely reach the stage of ulcer. Thus, first of all we would like to establish a few definitions and outline the scope of our review.


Peptic Ulcer Duodenal Ulcer Gastric Ulcer Stress Ulcer Gastric Injury 
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. 1.
    Bernandino ME, Lawson TL (1976) Discrete colonic ulcers associated with oral contraceptives. Dig Dis Sci 21: 503–506CrossRefGoogle Scholar
  2. 2.
    Briggs MH, Brotherton J (1970) Steroid biochemistry and pharmacology. Academic, Press, LondonGoogle Scholar
  3. 3.
    Bolton JP, Cohen MM (1978) Stimulation of non-parietal cell secretion in canine Heidenhain pouches by 16,16-dimethyl prostaglandin E2. Digestion 17: 291–299PubMedCrossRefGoogle Scholar
  4. 4.
    Bolton JP, Palmer D, Cohen MM (1976) Effect of the E2 prostaglandins on gastric mucus production in rats. Surg Forum 1976; 27: 402–403Google Scholar
  5. 5.
    Bolton JP, Palmer D, Cohen MM (1978) Stimulation of mucus and nonparietal cell secretion by the E2 prostaglandins. Am J Dig Dis 23: 359–364PubMedCrossRefGoogle Scholar
  6. 6.
    Brennan MF, Clarke AM, MacBeth WAAG (1969) Infarction of the midgut associated with oral contraceptives: report of two cases. N Engl J Med 279: 1213–1214CrossRefGoogle Scholar
  7. 7.
    Carbone JV, Leibowitz D, Forsham P (1957) Suppression of prednisone-induced gastric hypersecretion by an anticholinergic drug. Proc Soc Exp Biol Med 94: 293–294PubMedGoogle Scholar
  8. 8.
    Chaikof L, Janke WH, Pesaros PC, Ponka JL, Brush BE (1961) Effect of prednisolone and corticotropin secretion. Arch Surg 83: 32–46PubMedCrossRefGoogle Scholar
  9. 9.
    Cirino G, Sorrentino L (1986) Phospholipase inhibition and prostacyclin generation by gastric muscularis and mucosa layers. Agents Actions 18: 535PubMedCrossRefGoogle Scholar
  10. 10.
    Clarke SD, Neill D W, Welbourn RB (1960) The effects of corticotropin and cor-ticoids on secretion from denervated gastric pouches on dogs. Gut 1: 36–43PubMedCrossRefGoogle Scholar
  11. 11.
    Conn HO, Blitzer BL (1976) Nonassociation of adrenocorticosteroid therapy and peptic ulcer. N Engl J Med 294: (9) 473–479PubMedCrossRefGoogle Scholar
  12. 12.
    Cotton PB, Thomas ML (1971) Ischemic colitis and the contraceptive pill Br Med J 3: 27–28Google Scholar
  13. 13.
    Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or heparin fragment. Science 230: 1375–1378PubMedCrossRefGoogle Scholar
  14. 14.
    Delaney JP, Michel HM, Bonsack ME, Eisenberg MM, Dunn DH (1978) Adrenal corticosteroids cause gastrin cell hyperplasia. Gastroenterology 76: 913–916Google Scholar
  15. 15.
    Denko C W (1958) The effect of hydrocortisone and cortisone on fixation of S 35 in the stomach. J Lab Clin Med 51: 174–177PubMedGoogle Scholar
  16. 16.
    Derelanko MJ, Long JF (1982) Influence of prednisolone on ethanol-induced gastric injury in rat Dig Dis Sci 27: 149–154PubMedCrossRefGoogle Scholar
  17. 17.
    Fitzsimons R, Grammer LC, Halwig JM, Aksamit T, Patterson L (1988) Prevalence of adverse effects in corticosteroid dependent asthmatics. New Engl Reg Allergy Proc 9 (2): 157–162CrossRefGoogle Scholar
  18. 18.
    Flower RJ, Blackwell GJ (1979) Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature 278: 456PubMedCrossRefGoogle Scholar
  19. 19.
    Foley WA, Glick D (1962) Studies on histochemistry: LXVI. Histamine, mast and parietal cells in stomach of rats and effects of cortisone treatment. Gastroenterology 43: 425–429PubMedGoogle Scholar
  20. 20.
    Folkman J, Ingber DE (1987) Angiostatic steroids. Ann Surg 206 (3): 374–383PubMedCrossRefGoogle Scholar
  21. 21.
    Folkman J, Szabo S, Stovroff N, McNeil P, Li W, Shing Y (1991) Duodenal ulcer: discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg 214: 414–426PubMedCrossRefGoogle Scholar
  22. 22.
    Fung WP, Lee SK, Karim SMM (1974) Effect of prostaglandin 15(R)-15-methyl E2-methyl ester on the gastric mucosa in patients with peptic ulcer action. An endoscopic and histologic study. Prostaglandins 5: 465–472PubMedCrossRefGoogle Scholar
  23. 23.
    Garner A, Heylinds JR, Hampson SE, Stanier AM (1990) Pharmacological profile of duodenal alkaline secretion. Alimentary Pharmacol. Ther 4: 465–476CrossRefGoogle Scholar
  24. 24.
    Gelfand MD (1972) Ischemic colitis associated with a depot synthetic progesterone. Dig Dis Sci 17: 275–277CrossRefGoogle Scholar
  25. 25.
    Giampaolo C, Gray AT, Olshen RA, Szabo S (1991) Predicting chemically induced duodenal ulcer and adrenal necrosis with classification trees. Proc Natl Acad Sci 88: 6298–6302PubMedCrossRefGoogle Scholar
  26. 26.
    Goldman H, Szabo S (1992) Chemical and physical disorders. In: Ming SC, Goldman H (eds) Pathology of the gastrointestinal tract. Saunders, Philadelphia; pp 141–170Google Scholar
  27. 27.
    Gray SJ, Ramsey CG, Villereal R, Krakauer LJ (1955) Adrenal influences upon the stomach and the gastric response to stress. In: Selye, H, Heuser G (eds) Fifth annual report on stress 1955–1956; Acta Inc Med Publishers. Montreal, pp 138–160Google Scholar
  28. 28.
    Gryglewski RJ, Panczenko B, Korbut R Grrodzinska L, Ocetiwicz A (1975) Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pigs. Prostaglandins 10: 343–355PubMedGoogle Scholar
  29. 29.
    Guslandi M (1990) Gastric mucus. In: Scarpignato C, Bianchi Porro G (eds) Clinical investigation of gastric function. Karger, Basel, pp 103–126Google Scholar
  30. 30.
    Guslandi M, Tittobello A (1992) Steroid ulcers: a myth revisited. B M J 304: 655–656CrossRefGoogle Scholar
  31. 31.
    Hoyle M, Kennedy A, Prior AL et al. (1977) Small bowel Ischaemia and infarction in young women taking oral contraceptives and progestational agents. Br J Surg 64: 533–537PubMedCrossRefGoogle Scholar
  32. 32.
    Janowitz HD, Weinstein VA, Shaer RG, Cereghini JF, Hollander F (1958) The effect of cortisone and corticotropin on the healing of gastric ulcer: an experimental study. Gastroenterology 34: 11–20PubMedGoogle Scholar
  33. 33.
    Kahn DS, Phillips M J, Skoryna SC (1961) Healed experimental gastric ulcer in rat: reulceration resulting from cortisone administration. Arch Pathol 38:177–187Google Scholar
  34. 34.
    Kawarada Y, Lambek J, Matsumoto T (1975) Pathophysiology of stress ulcer and its prevention II. Prostaglandin E1 and microcirculatory responses in stress ulcer. Am J Surg 129: 217–222PubMedCrossRefGoogle Scholar
  35. 35.
    Kelly P, Robert A (1969) Inhibition by pregnancy and lactation of steroid induced ulcers in rat. Gastroenterology 56: 24–29PubMedGoogle Scholar
  36. 36.
    Kilpatrick ZM, Silverman JF, Betancourt E et al (1968) Vasvular occlusion of the colon and oral contraceptives. N Engl J Med 278: 438–440PubMedCrossRefGoogle Scholar
  37. 37.
    Kuroiwa M, Sugiyama S, Tsukamoto Y, Goto H, Ohara A, Hosoino H et al. (1991) Effect of NSAIDs and steroids on healing of ethanol-induced gastric lesions in rats: steroids are not noxious agents against gastric injury. Gastroenterology 100: A102Google Scholar
  38. 38.
    Lancester C, Robert A (1978) Intestinal lesions produced by prednisolone: prevention (cytoprotection) by 16,16-dimethyl prostaglandin E2. Am J Physiol 235: E703Google Scholar
  39. 39.
    Menguy R, Masters YF (1963) Effect of cortisone on mucoprotein secretion by gastric antrum of dogs: pathogenesis of steroid ulcer. Surgery 54: 19–28PubMedGoogle Scholar
  40. 40.
    Messer J, Reitman D, Sacks HS, Smith H, Chalmers TC (1983) Association of corticosteroid therapy and peptic ulcer disease. N Engl J Med 309: 21–24PubMedCrossRefGoogle Scholar
  41. 41.
    Mozsik GY, Suto G, Vincze A, Zsoldos T (1987) Correlation between free radicals and membrane-dependent energy systems in ethanol-induced gastric mucosal damage in rats. In: Szabo S, Pfeiffer CJ (eds) Ulcer disease. CRC, Boca Raton, pp 15–29Google Scholar
  42. 42.
    Niwa Y, Iio A, Niwa G, Sakane T, Tsunematsu T, Kanoh T (1990) Serum albumin metabolism in rheumatic diseases: relationship to corticosteroids and peptic ulcer. J Clin Lab Immunol 31: 11–16PubMedGoogle Scholar
  43. 43.
    Nobuhara Y, Ueki S, Takeuchi K (1985) Influence of prednisolone on gastric alkaline response in rat stomach. A possible explanation for steroid-induced gastric lesion. Dig Dis Sci 30: 1166PubMedCrossRefGoogle Scholar
  44. 44.
    Nobuhara Y, Ueki S, Takeuchi K et al. (1985) Influence of prednisolone on gastric alkaline response in rat stomach. Dig Dis Sci 30: 1166–1173PubMedCrossRefGoogle Scholar
  45. 45.
    Piper JM, Ray WA, Daughterty JR Griffin MR (1991) Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Int Med 114: 735–740PubMedGoogle Scholar
  46. 46.
    Plainos TC, Niktopulu GK, Vudykis PK (1962) The effect of triamcinolone and dexamethasone on gastric secretion and the excretion of uropepsin tested in dogs. Gastroenterology 43: 448–456PubMedGoogle Scholar
  47. 47.
    Poynard T (1990) Critical study of gastroduodenal complications of cortico-therapy. Rev Practicien 40: 553–555Google Scholar
  48. 48.
    Reid NC, Hackett RM, Welbourn RB (1961) The influence of cortisone on the parietal cell population of the stomach in the dog. Gut 2: 119–122PubMedCrossRefGoogle Scholar
  49. 49.
    Rhodes JM, Cockel R, Allan RN et al. (1984) Colonic Crohn’s disease and use of oral contraception. B M J 288: 595–596CrossRefGoogle Scholar
  50. 50.
    Robert A (1973) Prostaglandins and the digestive system. In Prostaglandines. INSERM, Paris, pp 297–315Google Scholar
  51. 51.
    Robert A (1979) Cytoprotection by prostaglandins, Gastroenterology 77: 761–767PubMedGoogle Scholar
  52. 52.
    Robert A, Nezamis JE (1959) Prevention of steroid-induced ulcers with an anticholinergic drug. Proc Soc Exp Biol Med 100: 596–597PubMedGoogle Scholar
  53. 53.
    Robert A, Nezamis JE (1963) Effect of prednisolone on gastric mucus content and ulcer formation. Proc Soc Exp Biol Med 114: 545–550PubMedGoogle Scholar
  54. 54.
    Robert A, Nezamis JE (1963) Ulcerogenic property of steroids. Proc Soc Exp Biol Med 114: 545–550PubMedGoogle Scholar
  55. 55.
    Robert A, Nezamis JE (1964) Effect of an anti-acetylcholine drug, methscopol-amine bromide on ulcer formation and gastric mucus. J Pharm Pharmacol 16: 690–695PubMedCrossRefGoogle Scholar
  56. 56.
    Robert A, Nezamis JE (1964) Histopathology of steroid induced ulcers. An experimental study in the rat Arch Pathol 77: 407–423Google Scholar
  57. 57.
    Robert A, Szabo S (1983) Stress ulcers. In: Selye H (ed) Selye’s guide to stress research. Scientific and Academic Edition 2: 22–46Google Scholar
  58. 58.
    Robert A, Phillips JP, Nezamis JE (1966) Prevention of ulcer formation by hypo-physectomy. Proc Soc Exp Biol Med 121: 992–995PubMedGoogle Scholar
  59. 59.
    Robert A, Phillips JP, Nezamis JE (1966) Gastric secretion and ulcer formation after hypophysectomy and administration of somatotrophic hormone. Am J Dig Dis 11: 516–522CrossRefGoogle Scholar
  60. 60.
    Robert A, Nezamis JE, Phillips JP (1968) Effect of prostaglandin E1 on gastric secretion and ulcer formation in the rat. Gastroenterology 55: 481–487PubMedGoogle Scholar
  61. 61.
    Robert A, Schultz JR, Nezamis JE, Lancester C (1976) Gastric antisecretory and antiulcer properties of PGE2, 15-methyl PGE2, and 16,16-dimethyl PGE2. Intravenous, oral and intrajejunal administration. Gastroenterology 70: 359–370PubMedGoogle Scholar
  62. 62.
    Robert A, Nezamis JE, Lancester C, Hanchar A J (1977) Gastric cytoprotective property of prostaglandins. Gastroenterology 72: 1121Google Scholar
  63. 63.
    Robert A, Nezamis JE, Lancester C, Hanchar AJ (1979) Cytoprotection by prostaglandins in rats: prevention of gastric necrosis by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury. Gastroenterology 77: 433–443PubMedGoogle Scholar
  64. 64.
    Ruppin H, Person B, Domschke W et al. (1979) Zytoprotektive Wirkungen von Prostaglandin E2 auf die Magenschleimhaut beim Menschen. Dtsch Med Wochenschr 104: 1457–1458PubMedGoogle Scholar
  65. 65.
    Ruppin H, Person B, Robert A et al. (1979) Gastric cytoprotection by prostaglandins (PG): possible medication by mucus secretion. Physiologist 22: 110Google Scholar
  66. 66.
    Scott J (1981) Physiological, pharmacological and pathological actions of glucocorticoids on the digestive system. Clin Gastroenterol 10: 62Google Scholar
  67. 67.
    Selye H (1936) A syndrome produced by diverse nocuous agents. Nature 138: 32CrossRefGoogle Scholar
  68. 68.
    Selye H (1941) Anesthetic effect of steroid hormones. Proc Soc Exp Biol Med 46: 116–121Google Scholar
  69. 69.
    Selye H (1941) Pharmacological classification of steroid hormones. Nature 148: 84–85CrossRefGoogle Scholar
  70. 70.
    Selye H (1942) Correlation between the chemical structure and the pharmacological actions of the steroids. 30: 437–453Google Scholar
  71. 71.
    Selye H (1942) Production of nephrosclerosis by overdosage with desoxyeorticos-terone acetate. Can Med Ass J 47: 515–519PubMedGoogle Scholar
  72. 72.
    Selye H (1943) An attempt at a natural classification of the steroids. Nature 151: 662–667CrossRefGoogle Scholar
  73. 73.
    Selye H (1944) Role of the hypophysis in the pathogenesis of the diseases of adaptation. 50: 426–433Google Scholar
  74. 74.
    Selye H (1950) Stress. Montreal Acta, Inc, MontrealGoogle Scholar
  75. 75.
    Selye H (1971) Hormones and resistance. Springer, New YorkGoogle Scholar
  76. 76.
    Selye H (1976) Stress in health and disease. Butterworths, BostonGoogle Scholar
  77. 77.
    Selye H, Dosne C (1940) Treatment of wound shock with corticosterone. Lancet 2: 70CrossRefGoogle Scholar
  78. 78.
    Spiro HM (1983) Is steroid ulcer a myth? N Engl J Med 309: 405–407CrossRefGoogle Scholar
  79. 79.
    Szabo S (1978) Animal model of human disease: duodenal ulcer disease; animal model: cysteamine-induced acute and chronic duodenal ulcer in rat Am J Pathol 93: 273–276PubMedGoogle Scholar
  80. 80.
    Szabo S (1980) Stress and gastroduodenal ulcers. Stress 1: (2) 25–36Google Scholar
  81. 81.
    Szabo S (1985) The antiangiogenic activity of hydrocortisone is independent of its glucocorticoid activity. In: Folkman J (ed) Toward an understanding of angio-genesis: search and dicovery. Perspect Biol Med 29: 29Google Scholar
  82. 82.
    Szabo S (1991) Mechanisms of gastric mucosal injury and protection. J Clin Gastroenterol 13 [Suppl 2]: S21-S34PubMedCrossRefGoogle Scholar
  83. 83.
    Szabo S, Cho CH (1988) From cysteamine to MPTP: structure-activity studies with duodenal ulcerogens. Toxicol Pathol 16: 205–212PubMedCrossRefGoogle Scholar
  84. 84.
    Szabo S, Gallagher GT, Horner HC, Frankel PV, Underwood RH, Kontwoek SJ et al. (1983) Role of adrenal cortex in gastric mucosal protection by prostaglandins, sulfhydryls and Cimetidine in the rat. Gastroenterology 85: 1384–1390PubMedGoogle Scholar
  85. 85.
    Szabo S, Vattay P, Morales RE (1989) Orally administered bFGF mutein: effect on healing of chronic duodenal ulcers in rats. Dig Dis Sci 34: 1323Google Scholar
  86. 86.
    Szabo S, Vattay P, Morales RE, Saha B, Neumayer JL, Lequesne PW (1991) Effect of a new class of steroids on healing of experimental chronic duodenal ulcers. Gastroenterology 100: A171Google Scholar
  87. 87.
    Tedesco FJ, Volpicelli NA, Moore F S (1982) Estrogen- and progesterone-associated colitis: a disorder with clinical and endoscopic features mimicking Crohn’s colitis. Gastrointest Endosc 28: 247–249PubMedCrossRefGoogle Scholar
  88. 88.
    Wallace JL (1987) Glucocorticoid-induced gastric mucosal damage: Inhibition of leukotriene, but not prostaglandin biosynthesis. Prostaglandins 34: 311–323PubMedCrossRefGoogle Scholar
  89. 89.
    Wallace JL, Whittle B JR (1988) Gastrointestinal damage induced by platelet-activating factor. Inhibition by corticoid dexamethasone. Dig Dis Sci 33: 225–232PubMedCrossRefGoogle Scholar
  90. 90.
    Whittle B JR (1978) Potential endogenous inhibitor of prostaglandin synthetase in plasma: failure to inhibit cyclo-oxygenase in platelets and gastric mucosa. J Pharm Pharmacol 30: 467PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Z. Sandor
    • 1
  • S. Szabo
    • 1
  1. 1.Chemical Pathology Research Division, Dept. of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

Personalised recommendations