Abstract
Moderate to severe functional bowel disease results in debilitating abdominal pain, nausea, intermittent vomiting, early satiety, bloating, abdominal distension, and/or altered bowel habits. Because it occurs ∼20–30 times more frequently in women than in men and its symptoms often coincide with the menstrual cycle, we hypothesized that reproductive steroids may antagonize diseased nerves of the gastrointestinal tract, enhancing the expression of symptoms. No effective or consistent therapy has existed for these patients. We prospectively investigated the effect of a gonadotropin-releasing hormone analog, leuprolide acetate, in 30 women with symptoms of moderate to severe functional bowel disease. The study was phase II, randomized, double blind, and placebo controlled. Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo were given intramuscularly monthly for three months. Symptom scores were assessed at each four-week visit. Follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone levels were assessed before and after therapy. Patients treated with low-dose leuprolide improved progressively and significantly in scores for nausea, vomiting, bloating, abdominal pain, and early satiety, and for overall symptoms (P<0.01–0.05). All hormone levels decreased significantly (P<0.05) except luteinizing hormone (P=0.054).
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Mathias JR, Finelli DS: Functional diseases of the small intestine.In Functional Disorders of the Gastrointestinal Tract, Contemporary Issues in Gastroenterology, Vol. 6. S Cohen, RD Soloway (eds). New York, Churchill Livingstone, 1987, pp 39–58
Reeves-Darby VG, Mathias JR: Motility disorders of the small intestine: Pseudo-obstruction syndromes. Contemp Intern Med 3:92–113, 1991
Chokhavatia S, Anuras S: Neuromuscular disease of the gastrointestinal tract. Am J Med Sci 301:201–214, 1991
Mitchell CM, Drossman DA: Survey of the AGA membership relating to patients with functional gastrointestinal disorders. Gastroenterology 92:1282–1284, 1987
Davis RH, Clench MH, Mathias JR: Effects of domperidone in patients with chronic unexplained upper gastrointestinal symptoms: A double-blind, placebo-controlled study. Dig Dis Sci 33:1501–1511, 1988
Camillari M, Malagelada JR, Abell TL, Brown ML, Henck V, Zinsmeister AR: Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudo-obstruction. Gastroenterology 96:704–712, 1989
Schuffler MD, Pope CE II: Studies of idiopathic intestinal pseudo-obstruction II. Hereditary hollow visceral myopathy: Familial studies. Gastroenterology 73:339–344, 1977
Smout AJPM, De Wilde K, Kooyman CD, Ten Thije OJ: Chronic idiopathic intestinal pseudo-obstruction: Coexistence of smooth muscle and neuronal abnormalities. Dig Dis Sci 30:282–287, 1985
Krishnamurthy S, Schuffler MD, Rohrmann CA, Pope CE II: Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology 88:26–34, 1985
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, 1989
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, 1981
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, 1982
Amoss M, Burgus R, Blackwell R, Vale W, Fellows R, Guillemin R: Purification, amino acid composition, andN-terminus of the hypothalamic luteinizing hormone releasing factor (LRF) of bovine origin. Biochem Biophys Res Commun 44:205–210, 1971
Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, Nair RM, Debeljuk L, White WF: Gonadotropin-releasing hormone: One polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science 173:1036–1038, 1971
Hazum E, Conn PM: Molecular mechanism of gonadotropin releasing hormone (GnRH) action. I. The GnRH receptor. Endocrinol Rev 9:379–386, 1988
Clayton RN, Catt KJ: Regulation of pituitary gonadotropin releasing hormone receptors by gonadal hormones. Endocrinology 108:887–895, 1981
Yen SSC, Lein A: Mammals: Man.In Reproductive Cycles of Vertebrates, Vol. 1 of Marshall's Physiology of Reproduction, 4th ed., GE Lamming (ed). Edinburgh, Churchill Livingstone, 1984, pp 713–788
Conn PM, Hsueh AJW, Crowley WF Jr: Gonadotropin-releasing hormone: Molecular and cell biology, physiology, and clinical applications. Fed Proc 43:2351–2361, 1984
Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E: Hypophysial responses to continuous and intermittent delivery of hypothalamic gonadotropin-releasing hormone. Science 202:631–633, 1978
Dowsett M, Cantwell B, Anshumala L, Jeffcoate SL, Harris AL: Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin. J Clin Endocrinol Metab 66:672–677, 1988
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, 1985
Coy DH, Vilchez-Martinez JA, Coy EJ, Schally AV: Analogs of luteinizing hormone-releasing hormone with increased biological activity produced byd-amino acid substitutions in position 6. J Med Chem 19:423–425, 1976
Hersh LB, McKelvy JF: Enzymes involved in the degradation of thyrotropin releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) in bovine brain. Brain Res 68:553–564, 1979
Wilk S, Benuck M, Orlowski M, Marks N: Degradation of luteinizing hormone-releasing hormone (LH RH) by brain prolyl endopeptidase with release of des-glycinamide LH RH and glycinamide. Neurosci Lett 14:275–279, 1979
Hazum E, Fridkin M, Baram T, Koch Y: Degradation of gonadotropin-releasing hormone by anterior pituitary enzymes. FEBS Lett 127:273–276, 1981
Kochman K, Kerdelhué B, Zor U, Jutisz M: Studies of enzymatic degradation of luteinizing hormone-releasing hormone by different tissues. FEBS Lett 50:190–194, 1975
Loumaye E, Naor Z, Catt KJ: Binding affinity and biological activity of gonadotropin releasing hormone agonists in isolated pituitary cells. Endocrinology 111:730–736, 1982
Yen SSC: Clinical applications of gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Fertil Steril 39:257–266, 1983
Vickery BH: Comparison of the potential for therapeutic utilities with gonadotropin-releasing hormone agonists and antagonists. Endocrinol Rev 7:115–124, 1986
Conn PM, Crowley WF Jr: Gonadotropin-releasing hormone and its analogues. N Engl J Med 324:93–103, 1990
Mathias JR, Sninsky CA, Millar HD, Clench MH, Davis RH: Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine. Dig Dis Sci 30:119–123, 1985
Heitkemper MM, Jarrett M: Pattern of gastrointestinal and somatic symptoms across the menstrual cycle. Gastroenterology 102:505–513, 1992
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, 1992
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)
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, 1992
Author information
Authors and Affiliations
Additional information
This material was published in abstract form inGastroenterology 104:A548, and presented at the annual meeting of the American Gastroenterological Association, Boston, Massachusetts, May 15–21, 1993.
This study was supported by a grant from TAP Pharmaceuticals Inc., Deerfield, Illinois.
Rights and permissions
About this article
Cite this article
Mathias, J.R., Clench, M.H., Reeves-Darby, V.G. et al. Effect of leuprolide acetate in patients with moderate to severe functional bowel disease. Digest Dis Sci 39, 1155–1162 (1994). https://doi.org/10.1007/BF02093778
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02093778