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Effect of Leuprolide Acetate in Treatment of Abdominal Pain and Nausea in Premenopausal Women with Functional Bowel Disease: A Double-Blind, Placebo-Controlled, Randomized Study

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Abstract

We have previously reported impressive results in using a gonadotropin-releasing hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to severe symptoms (especially abdominal pain and nausea) in patients with functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and there is no consistent therapy for the treatment of these patients. The purpose of the present study was to expand the investigation to study similar patients (menstruating females) in a multicenter, double-blind, placebo-controlled, randomized study using Lupron Depot (which delivers a continuous dose of drug for one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia, bloating, and altered bowel habits. Additional assessment tools were quality of life questionnaires, psychological profile, oralto-cecal transit using the hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and global evaluations by both patient and investigator. Patients in both Lupron Depot-treated groups showed consistent improvement in symptoms; however, only the Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and nausea compared to placebo (P < 0.001). Patient quality of life assessments and global evaluations completed by both patient and investigators were highly significant compared to placebo (P < 0.001). All reproductive hormone levels significantly decreased for both Lupron Depot-treated groups by week 4 and were significantly different compared to placebo at week 16 (P < 0.001). This study shows that leuprolide acetate is effective in controlling the debilitating symptoms of abdominal pain and nausea in patients with FBD.

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REFERENCES

  1. Mitchell CM, Drossman DA: Survey of the AGA membership relating to functional gastrointestinal disorders. Gastroenterology 92:1283-1284, 1987

    Google Scholar 

  2. Rohrmann CA Jr, Ricci MT, Krishnamurthy S, Schuffler MD AJR: Radiographic and histologic differentiation of neuromuscular disorders of the gastrointestinal tract: Visceral myopathies, visceral neuropathies, and progressive systemic sclerosis. Am J Roentgenol 143(5):933-941, 1984

    Google Scholar 

  3. Mathias JR, Clench MH: Neuromuscular diseases of the gastrointestinal tract. Postgrad Med 97:95-108, 1995

    Google Scholar 

  4. Mathias JR, Finelli SR: Functional disorders of the small intestine. InFunctional Disorders of the Gastrointestinal Tract (Contemporary Issue s of in Gastroenterology, Vol 6). S Cohen, RD Soloway (eds). New York, Churchill Livingstone, 1987, pp 39-58

    Google Scholar 

  5. Drossman DA, Thompson WG, Talley NJ, Funch-Jensen P, Janssens J, Whitehead WE: Identification of sub-groups of functional bowel disorders. Gastroenterol Int 3:159-172, 1990

    Google Scholar 

  6. Talley NJ, Fleming KC, Evans JM, O'Keefe EA, Weaver AL, Zinsmeister AR, Melton LJ 3rd: Constipation in an elderly community: A study of prevalence and potential risk factors. Am J Gastroenterol 91(1):19-25, 1996

    Google Scholar 

  7. 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 33:1505-1511, 1988

    Google Scholar 

  8. Koussayer T, Clench MH, Mathias JR: Ampulla of Vater/ Duodenal Wall Spasm diagnosed by small bowel manometry in patients with unexplained abdominal pain, nausea, and vomiting. Dig Dis Sci 40:1710-1719, 1995

    Google Scholar 

  9. 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

    Google Scholar 

  10. Mathias JR, Ducker TE: Intestinal obstruction and ileus. InIntensive Care Medicine, 3rd ed. JM Rippe, RS Irwin, MP Fink, RB Cerra (eds). Boston, Little, Brown and Company, 1996, pp 1244-1253

    Google Scholar 

  11. Smout AJPN, DeWilde K, Kooyman CD, Ten Thije OJ: Chronic idiopathic intestinal pseudo-obstruction, coexistence of smooth muscle and neuronal abnormalities. Dig Dis Sci 30:282, 1985

    Google Scholar 

  12. 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

    Google Scholar 

  13. Mathias JR, Clench MH, Reeves-Darby VG, Mehelich Fox L, Ping HH, Roberts PH, Smith LL, Stiglich NJ: Effect of leuprolide acetate in patients with moderate to severe functional bowel disease. Dig Dis Sci 39:1155-1162, 1994

    Google Scholar 

  14. Mathias JR, Clench MH, Roberts PH, Reeves-Darby VG: Effect of leuprolide acetate in patients with functional bowel disease: Long-term follow up after double-blind, placebocontrolled study. Dig Dis Sci 39:1163-1170, 1994

    Google Scholar 

  15. Jenkins CD, Jono RT, Stanton BA, Stroup-Benham CA: The Measurement of health-related quality of life: Major dimensions identified by factor analysis. Soc Sci Med 31:925-931, 1990

    Google Scholar 

  16. 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

    Google Scholar 

  17. Mathias JR, Clench MH: Relationship of reproductive hormones and neuromuscular disease of the gastrointestinal tract. Dig Dis 16:3-13, 1998

    Google Scholar 

  18. Schally AV, Arimura A, Coy DH: Recent approaches to fertility control based on derivatives of LH-RH. Vitam Horm 38:257-323, 1980

    Google Scholar 

  19. Hazum E, Conn PM: Molecular mechanism of gonadotropin releasing hormone (GNRH) action. 1. The GnRH receptor. Endocrinol Rev 9:379-386, 1988

    Google Scholar 

  20. Knobil E: The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res 36:53-88, 1980

    Google Scholar 

  21. Conn PM: The molecular basis of gonadotropin-releasing hormone action. Endocrinol Rev 7:3-10, 1986

    Google Scholar 

  22. Huckle WR, Conn PM: Molecular mechanism of gonadotropin-releasing hormone action. 11. The effector system. Endocrinol Rev 9:387-395, 1988

    Google Scholar 

  23. Yen SSC, Lein A: Reproductive cycles of vertebrates: Mammals: Man. InMarshall's Physiology of Reproduction, 4th ed., Vol.1. GE Lamming (ed). Edinburgh, Churchill Livingstone, 1984, pp 713-788

    Google Scholar 

  24. Ducker TE, Boss JW, Altug SA, Mehrabian H, deKeratry DR, Clench MH, Mathias JR: Luteinizing hormone and human chorionic gonadotropin fragment the migrating myoelectric complex in rat small intestine. Neurogastroenterol Motil 8(2):95-100, 1996

    Google Scholar 

  25. deKeratry DR, Ducker TE, Clench MH, Mathias JR: Proge sterone and relaxin disrupt the migrating myoelectric complex (MMC) of the small intestine in rats. Gastroenterology 104:A1036, 1993

    Google Scholar 

  26. Koch KL, Stern RM, Vasey M, Botti JJ, Creasy GW, Dwyer A: Gastric dysrhythmias and nausea of pregnancy. Dig Dis Sci 35(8):961-968, 1990

    Google Scholar 

  27. Walsh J, Hasler W, Nugent C, Owyang C: Progesterone and estrogen are potential mediators in the nausea and vomiting of pregnancy. Am J Physiol 270:G506-G514, 1996

    Google Scholar 

  28. Tse A, Hille B: GnRH-induced Ca2+ oscillations and rhythmic hyperpolarizations of pituitary gonadotropes. Science 255:462- 464, 1992

    Google Scholar 

  29. Tse A, Hille B: Role of voltage-gated Na+ and Ca2+ channels in gonadotropin-releasing hormone-induced membrane potential changes in identified rat gonadotropes. Endocrinology 132:1475–1481, 1993

    Google Scholar 

  30. Bley KR, Tsien RW: Inhibition of Ca2+ and K+ channels in sympathetic neurons by neuropeptides and other ganglionic transmitters. Neuron 2:379–391, 1990

    Google Scholar 

  31. Emslie KS, Zhou W, Jones SW: LHRH and GTP-Y-S modify calcium current activation in bullfrog sympathetic neurons. Neuron 5:75–80, 1990

    Google Scholar 

  32. Boland LM, Bean BP: Modulation of N-type calcium channe ls in bullfrog sympathetic neurons in luteinizing hormone-releasing hormone: Kinetic and voltage dependence. J Neurosci 13:516–533, 1993

    Google Scholar 

  33. Stojilkovic SS, Tomic M: GnRH-induced calcium and current oscillations in gonadotrophs. Trends Endocrinol Metab 7(10):379-384, 1996

    Google Scholar 

  34. Muske LE: Evolution of gonadotropin-releasing hormone (GnRH) neuronal systems. Brain Behav Evol 42:215–230, 1993

    Google Scholar 

  35. Jennes L: Sites of origin of gonadotropin-releasing hormone containing projections to the amygdala and the interpeduncular nucleus. Brain Res 404:339–344, 1987

    Google Scholar 

  36. Jennes L, Stumpf WE: Gonadotropin-releasing hormone immunoreactive neurons with access to fenestrated capillaries in mouse brain. Neuroscience 18:403–416, 1986

    Google Scholar 

  37. Sen RN, Anand BK: Effect of electrical stimulation of the limbic system of brain (”visceral brain”) on gastric se cretary activity and ulceration. Ind J Med Res 45:515-521, 1957

    Google Scholar 

  38. Jan YN, Jan LY: Peptidergic transmission in sympathetic ganglia of the frog. J Physiol London 327:219-246, 1982

    Google Scholar 

  39. Ho JS, Nagle GT, Mathias JR, Clench MH, Fan X, Kalmaz GD, Sallustio JE, Eaker EY: Gonadotropin-releasing hormone (GNRH) receptor expressed in rat myenteric plexus cells. Comp Biochem Physiol (B) 113/4:817-821, 1996

    Google Scholar 

  40. King JA, Millar RP: Evolution of gonadotropin-releasing hormones. Trends Endocrinol Metab 3:339-346, 1992

    Google Scholar 

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Authors
  1. John R. Mathias
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  2. Mary H. Clench
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  3. Thomas L. Abell
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  4. Kenneth L. Koch
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  5. Glen Lehman
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  6. Malcolm Robinson
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  7. Robin Rothstein
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  8. William J. Snape
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Mathias, J.R., Clench, M.H., Abell, T.L. et al. Effect of Leuprolide Acetate in Treatment of Abdominal Pain and Nausea in Premenopausal Women with Functional Bowel Disease: A Double-Blind, Placebo-Controlled, Randomized Study. Dig Dis Sci 43, 1347–1355 (1998). https://doi.org/10.1023/A:1018888631286

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