Digestive Diseases and Sciences

, Volume 39, Issue 6, pp 1163–1170 | Cite as

Effect of leuprolide acetate in patients with functional bowel disease

Long-term follow-up after double-blind, placebo-controlled study
  • John R. Mathias
  • Mary H. Clench
  • Patricia H. Roberts
  • Vonda G. Reeves-Darby
Original Articles


We initially investigated the effects of a gonadotropin-releasing hormone analog, leuprolide acetate, in 28 patients with moderate to severe functional bowel disease in a phase-II, randomized, double-blind, and placebo-controlled study using Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo given intramuscularly. After completing that 12-week study period during which their symptoms had improved significantly (P<0.01–0.5), the 28 patients were allowed to continue receiving leuprolide acetate; they were monitored for an additional 40 weeks. Of those 28, 25 (89%) finished the 52-week treatment. Drug administration was changed from the monthly low-dose form of leuprolide acetate to a daily subcutaneous dose that was gradually increased from 0.5 mg daily to an effective therapeutic dose (1.0–1.5 mg). All subjects received estrogen replacement during this period. Continued use of leuprolide acetate at maximum therapeutic dosage and over longer periods of time produced even more striking and significant changes in the disabling and debilitating symptoms of functional bowel disease. Nausea, abdominal pain, early satiety, anorexia, and abdominal distension decreased markedly (P<0.0001) and vomiting was also reduced (P<0.01) more than in the short-term, low-dosage, double-blind study. Combined total symptom scores and overall assessment also changed significantly in the long-term phase (bothP<0.0001).

Key words

leuprolide acetate gonadotropin-releasing hormone functional bowel disease irritable bowel syndrome 


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  1. 1.
    Mathias JR, Clench MH, Reeves-Darby VG, Fox LM, Hsu PH, Roberts PH, Smith LL, Stiglich NJ: Effect of leuprolide acetate in patients with moderate-to-severe functional bowel disease: A double-blind, placebo-controlled study. Dig Dis Sci 39:1155–1162Google Scholar
  2. 2.
    Mathias JR, Finelli DS: Functional diseases of the small intestine.In Functional Disorders of the Gastrointestinal Tract. S Cohen, RD Soloway (eds). Contemporary Issues in Gastroenterology, Vol. 6. New York, Churchill Livingstone, 1987, pp 39–58Google Scholar
  3. 3.
    Reeves-Darby VG, Mathias JR: Motility disorders of the small intestine: Pseudo-obstruction syndromes. Contemp Intern Med 3:92–113, 1991Google Scholar
  4. 4.
    Chokhavatia S, Anuras S: Neuromuscular disease of the gastrointestinal tract. Am J Med Sci 301:201–214, 1991Google Scholar
  5. 5.
    Mitchell CM, Drossman DA: Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology 92:1282–1284, 1987Google Scholar
  6. 6.
    Mathias JR, Ferguson KL, Clench MH: Debilitating “functional” bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog. Dig Dis Sci 34:761–766, 1989Google Scholar
  7. 7.
    Mathias JR, Baskin GS, Reeves-Darby VG, Clench MH, Smith LL, Calhoon JH: Chronic intestinal pseudoobstruction in a patient with heart-lung transplant: Therapeutic effect of leuprolide acetate. Dig Dis Sci 37:1761–1768, 1992Google Scholar
  8. 8.
    Szlachter N, O'Byrne EM, Goldsmith L, Steinetz BG, Weiss G: Myometrial-inhibiting activity of relaxin containing extracts of human corpora lutea of pregnancy. Am J Obstet Gynecol 136:584–586, 1980Google Scholar
  9. 9.
    Beck P, Adler P, Szlachter N, Goldsmith LT, Steinetz BG, Weiss G: Synergistic effect of human relaxin and progesterone on human myometrial contractions. Int J Gynecol Obstet 20:141–144, 1982Google Scholar
  10. 10.
    Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, Scott L, Lester R: Intestinal transit: The effect of the menstrual cycle. Gastroenterology 80:1497–1500, 1981Google Scholar
  11. 11.
    Wald A, Van Thiel DH, Hoechstetter L, Gavaler JS, Egler KM, Verm R, Scott L, Lester R: Effect of pregnancy on gastrointestinal transit. Dig Dis Sci 27:1015–1018, 1982Google Scholar
  12. 12.
    Hazum E, Conn PM: Molecular mechanism of gonadotropin releasing hormone (GnRH) action. I. The GnRH receptor. Endocrinol Rev 9:379–386, 1988Google Scholar
  13. 13.
    Clayton RN, Catt KJ: Regulation of pituitary gonadotropin releasing hormone receptors by gonadal hormones. Endocrinology 108:887–895, 1981Google Scholar
  14. 14.
    Yen SSC, Lein A. Mammals: Man.In Reproductive Cycles of Vertebrates, Vol. 1, Marshall's Physiology of Reproduction, 4th ed. GE Lamming (ed). Edinburgh, Churchill Livingstone, 1984, pp 713–788Google Scholar
  15. 15.
    Yen SSC: Clinical applications of gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Fertil Steril 39:257–266, 1983Google Scholar
  16. 16.
    Vickery BH: Comparison of the potential for therapeutic utilities with gonadotropin-releasing hormone agonists and antagonists. Endocrinol Rev 7:115–124, 1986Google Scholar
  17. 17.
    Conn PM, Crowley WF Jr: Gonadotropin-releasing hormone and its analogues. N Engl J Med 324:93–103, 1990Google Scholar
  18. 18.
    Cutler GB Jr, Hoffman AR, Swerdloff RS, Santen RJ, Meldrum DR, Comite F: Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs (N.I.H. conference). Ann Intern Med 102:643–657, 1985Google Scholar
  19. 19.
    Snedecor GW, Cochran WG: Statistical Methods, 7th ed. Ames, Iowa, Iowa State University Press, 1980Google Scholar
  20. 20.
    Khanna R, Browne RM, Heiner AD, Clench MH, Mathias JR: Leuprolide acetate affects intestinal motility in female rats before and after ovariectomy. Am J Physiol 262:G185-G190, 1992Google Scholar
  21. 21.
    Heiner AM, Browne RM, Khanna R, Shinnick-Gallagher P, Callahan P, Clench MH, Mathias JR: Effect of centrally administered leuprolide acetate on myoelectric activity of the small intestine in rats. Gastroenterology 96:A202, 1989 (abstract)Google Scholar
  22. 22.
    Khanna R, Mathias JR, Kendall JZ, Lewis MT: Effect of leuprolide acetate (LA), a gonadotropin-releasing hormone analog, on contraction of longitudinal (LM) vs circular (CM) smooth musclein vitro. Gastroenterology 100:A457, 1991 (abstract)Google Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • John R. Mathias
    • 1
  • Mary H. Clench
    • 1
  • Patricia H. Roberts
    • 1
  • Vonda G. Reeves-Darby
    • 1
  1. 1.From the Department of Internal Medicine, Division of GastroenterologyThe University of Texas Medical BranchGalveston

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