Advertisement

Digestive Diseases and Sciences

, Volume 49, Issue 7–8, pp 1335–1341 | Cite as

Alterations in Gallbladder Emptying and Bile Retention in the Absence of Changes in Bile Lithogenicity in Postmenopausal Women on Hormone Replacement Therapy

  • Radha K. Dhiman
  • Pralay K. Sarkar
  • Arpita Sharma
  • Kala Vasishta
  • Krishan K. Kohli
  • Sanjay Gupta
  • Sudha Suri
  • Yogesh Chawla
Article

Abstract

The role of female sex hormones in the pathogenesis of gallstones is well established. Pregnancy, contraceptive use, estrogen replacement therapy in postmenopausal women, and estrogen therapy in men for the treatment of prostatic carcinoma have been found to be associated with increased risk of cholesterol gallstones. Alterations in gallbladder emptying and in bile lithogenicity in postmenopausal women receiving hormone replacement therapy (HRT) have not been studied to date. The present study was undertaken to study the effect of HRT on gallbladder emptying and bile lithogenicity. Sixteen postmenopausal women were included in the study. None of the patients had gallstone disease and none had received prokinetic drugs, such as, erythromycin, metoclopramide, domperidone or cisapride, aspirin, and nonsteroidal antiinflammatory drugs. Gallbladder emptying (n=16), bile microscopy (n=7), cholesterol saturation index (CSI) (n=7), and nucleation time (n=7) were studied before and 3 months after HRT (conjugated estrogen, 0.625 mg, + medroxyprogesterone acetate, 2.5 mg, everyday). Fasting and residual volumes increased (fasting volume, 18.2 ± 2.2 mL pre-HRT vs 27.6 ± 3.2 mL post-HRT, P = 0.0003; residual volume, 3.9 ± 0.6 mL pre-HRT vs 10.3 ± 2.0 mL post-HRT, P = 0.00009) and ejection fraction decreased (78.2 ± 2.5% pre-HRT vs 62.2 ± 3.8% post-HRT; P = 0.0017) after 3 months of HRT. There was no change in CSI (2.32 ± 0.36 pre-HRT vs 2.60 ± 0.51 post-HRT; P = NS) or in nucleation time (19.0 ± 1.2 days pre-HRT vs 17.6 ± 1.3 days post-HRT; P = NS). None of the bile samples either pre-HRT or post-HRT showed cholesterol monohydrate crystals. Though impairment of gallbladder emptying occurs in the short term with HRT in postmenopausal women, there is no change in CSI and nucleation time.

hormone replacement therapy gallbladder motility menopause bile estrogen progestin gallstones 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. 1.
    Diehl AK: Epidemiology and natural history of gallstone disease. Gastrointest Clin North Am 20:1–19, 1991Google Scholar
  2. 2.
    Maringhini A, Ciambra M, Baccelliere P, et al.: Biliary sludge and gallstones in pregnancy: Incidence, risk factors and natural history. Ann Intern Med 119:116–120, 1993Google Scholar
  3. 3.
    Leissner KH, Wedel H, Schersten T: Comparison between the use of oral contraceptives and the incidence of surgically con-firmed gallbladder disease. Scand J Gastroenterol 12:893–896, 1977Google Scholar
  4. 4.
    Scragg RK, McMichael AJ, Seamark RF: Oral contraceptives, pregnancy and endogenous estrogen in gallstone disease-A casecontrol study. Br Med J 288:1795–1799, 1984Google Scholar
  5. 5.
    Boston Collaborative Drug Surveillance Programme: Oral contraceptive, venous thromboembolic disease, surgically confirmed gallbladder disease and breat tumours. Lancet 1:1399–1404, 1973Google Scholar
  6. 6.
    Royal College of General Practitioners: Oral contraceptives and health. Manchester, UK, Pitman Medical, 1974, pp. 57–59Google Scholar
  7. 7.
    Uhler ML, Marks JW, Judd HL: Estrogen replacement therapy and gallbladder disease in postmenopausal women. Menopause 7:162–167, 2000Google Scholar
  8. 8.
    Vecchia CL, J Epidemiol Comm Health 46:234–236, 1992Google Scholar
  9. 9.
    Henriksson P, Einarsson K, Eriksson A, et al.: Estrogen induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. J Clin Invest 84:811–816, 1989Google Scholar
  10. 10.
    Donovan JM: Physical and metabolic factors in gallstone pathogenesis. Gastrointest Clin N Am 28:75–98, 1999Google Scholar
  11. 11.
    EversonGT, McKinleyC, Kern F Jr: Mechanism of gallstone formation inwomen. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism. J Clin Invest 87:237–246, 1991Google Scholar
  12. 12.
    Messa C, Maselli MA, Cavallini A, et al.: Sex steriod hormone receptors and human gallbladder motility in vitro. Digestion 46:214–219, 1990Google Scholar
  13. 13.
    Shaffer EA, Taylor PJ, Logan K, et al.: The effect of progestin on gallbladder function in young women. Am J Obstet Gynecol 148:504–507, 1984Google Scholar
  14. 14.
    Dodd W, Groh W, Darweesh R, et al.: Sonographic measurement of gallbladder volume. Am J Radiol 145:1009–1011, 1985Google Scholar
  15. 15.
    Dhiman RK, Reddi R, Sharma A, et al.: Cisapride improves gallbladder emptying and bile lipid composition in patients with gallstones. J Gastroenterol Hepatol 16:816–820, 2001Google Scholar
  16. 16.
    Dhiman RK, Arke L, Bhansali A, et al.: Cisapride improves gallbladder emptying in patients with diabetes mellitus. J Gastroenterol Hepatol 16:1044–1050, 2001Google Scholar
  17. 17.
    Dhiman RK, Phanish MK, Chawla YK, et al.: Gallbladder motility and lithogenicity of bile in patients with choledocholithiasis after endoscopic sphincterotomy. J Hepatol 26:1300–1305, 1997Google Scholar
  18. 18.
    Das A, Baijal SS, Saraswat VA: Effect of aspirin on gallbladder motility in patients with gallstone disease. A randomized, double blind, placebo control trial of two dosage schedules. Dig Dis Sci 40:1782–1785, 1995Google Scholar
  19. 19.
    Everson GT, Braverman DZ, Johnson ML, et al.: A critical evaluation of real time ultrasonography for the study of gallbladder volume and contraction. Gastroenterology 79:40–46, 1980Google Scholar
  20. 20.
    Juniper K Jr, Burson EN Jr: Significance of biliary crystals. Gastroenterology 32:175–96, 1957Google Scholar
  21. 21.
    Holan R, HolzbachRT, Hermann RE, et al.: Nucleation time-Akey factor in pathogenesis of gallstones. Gastroenterology 77:611–617, 1979Google Scholar
  22. 22.
    Marks JW, Broomfield P, Bonorris GG, et al.: Factors affecting the measurement of cholesterol nucleation in human gallbladder and duodenal bile. Gastroenterology 101:214–219, 1991Google Scholar
  23. 23.
    Sharma BC, Agarwal DK, Dhiman RK, et al.: Bile lithogenicity and gallbladder emptying in patients with microlithiasis: Effect of bile acid therapy. Gastroenterology 115:124–128, 1998Google Scholar
  24. 24.
    Leffler HH: Estimation of cholesterol in serum. Am J Clin Pathol 31:310–313, 1959Google Scholar
  25. 25.
    Fiske CH, Subbarow Y: The colorimetric determination of phosphorus. J Biol Chem 66:375–378, 1925Google Scholar
  26. 26.
    Turley SD, Dietschy JM: Re-evaluation of the 3a-hydroxysteroid dehydrogenase assay for total bile acids in bile. J Lipid Res 19:924–928, 1978Google Scholar
  27. 27.
    Carey MC: Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res 19:945–955, 1978Google Scholar
  28. 28.
    BCDSP: Surgically confirmed gallbladder disease, venous thromboembolism and breast tumors in relation to postmenopausal estrogen therapy. A report from the Boston Collaborative Drug Surveillance Program. Boston University Medical Center. N Engl J Med 290:15–19, 1974Google Scholar
  29. 29.
    Honore LH: Increased incidence of symptomatic cholesterol cholelithiasis in perimenopausal women receiving estrogen replacement therapy: A retrospective study. J Reprod Med. 25:187–190, 1980Google Scholar
  30. 30.
    Petitti DB, Friedman GD, Klatsky AL: Association of a history of gallbladder disease with a reduced concentration of high-densitylipoprotein cholesterol. N Engl J Med 304:1396–1398, 1981Google Scholar
  31. 31.
    Petitti DB, Sidney S, Perlman JA: Increased risk of cholecystectomy in users of supplemental estrogen. Gastroenterology. 94:91–95, 1988Google Scholar
  32. 32.
    La Vecchia C, Negri E, D'Avanzo B, et al.: Oral contraceptives and non-contraceptive oestrogens in the risk of gallstone disease requiring surgery. J Epidemiol Commun Health 46:234–236, 1992Google Scholar
  33. 33.
    Grodstein F, Colditz GA, Stampfer MJ: Postmenopausal hormone use and cholecystectomy in a large prospective study. Obstet Gynecol 83:5–11, 1994Google Scholar
  34. 34.
    Simon IA, Hunninghake DB, Agarwal SK, Lin F, Cauley JA, Ireland CC, Picker JH, for Heart and Estrogen/Progestion Replacement Study (HERS) research group. Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. Ann Intern Med 135:493–501, 2001Google Scholar
  35. 35.
    CDP: Gallbladder disease as a side effect of drugs influencing lipid metabolism. Experience in the Coronary Drug Project. N Engl J Med 296:1185–1190, 1977Google Scholar
  36. 36.
    Kakar F, Weiss NS, Strite SA: Non-contraceptive use and risk of gallstone disease in women. Am J Public Health 78:564–566, 1988Google Scholar
  37. 37.
    Jorgensen T: Gall stones in a Danish population: Fertility period, pregnancies, and exogenous female sex hormones. Gut 29:433–439, 1988Google Scholar
  38. 38.
    Pomeranz IS, Shaffer EA: Abnormal gallbladder emptying in a subgroup of patients with gallstones. Gastroenterology 88:787–791, 1985Google Scholar
  39. 39.
    Fridhandler TM, Davison JS, Shaffer EA: Defective gallbladder contractility in the ground squirrel and prairie dog during the early stages of cholesterol gallstone formation. Gastroenterology 85:830–836, 1983Google Scholar
  40. 40.
    Jazrawi RP, Pazzi P, Petroni ML, et al.: Postprandial gallbladder motor function: Refilling and turnover of bile in health and in cholelithiasis.Gastroenterology 109:582–591, 1995Google Scholar
  41. 41.
    Braverman DZ, Johnson ML, Kern F Jr: Effects of pregnancy and contraceptive steroids on gallbladder function. N Engl J Med 302:362–364, 1980Google Scholar
  42. 42.
    Hould FS, Fried GM, Fazekas AG, et al.: Progesterone receptors regulate gallbladder motility. J Surg Res 45:505–512, 1988Google Scholar
  43. 43.
    Davis M, Ryan JP: Influence of progesterone on guinea pig gallbladder motility in vitro. Dig Dis Sci 31:513–518, 1986Google Scholar
  44. 44.
    Ryan JP: Effects of pregnancy on gallbladder contractility in the guinea pig. Gastroenterology 87:674–678, 1984Google Scholar
  45. 45.
    Ryan JP, Pellecchia D: Effect of progesterone treatment on guinea pig gallbladder motility in vitro. Gastroenterology 83:81–83, 1982Google Scholar
  46. 46.
    Gilloteaux J, Karkare S, DonAQ, et al.: Cholelithiasis induced in the Syrian hamster: Evidence for an intramucinous nucleating process and down regulation of cholesterol 7 alpha-hydroxylase (CYP7) gene by medroxyprogesterone. Microsc Res Tech 39:56–70, 1997Google Scholar
  47. 47.
    Chen Q, Amaral J, Biancani P, et al.: Excess membrane cholesterol alters human gallbladder muscle contractility and membrance fluidity. Gastroenterology 116:678–685, 1999Google Scholar
  48. 48.
    Whiting MJ, Down RHL, Watts JMcK: Precision and accuracy in the measurement of cholesterol saturation of bile. Gastroenterology 80:533–538, 1981Google Scholar
  49. 49.
    Kern F Jr, Everson GT, DeMark B, et al.: Biliary lipids, bile acids, and gallbladder function in the human female: Effects of pregnancy and ovulatory cycle. J Clin Invest 68:1229–1242, 1981Google Scholar
  50. 50.
    Valdivieso V, Covarrubias C, Siegel F, et al.: Pregnancy and cholelithiasis: Pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 17:1–4, 1993Google Scholar
  51. 51.
    van Erpecum KJ, van Berge Henegouwen GP, Verschoor L, et al.: Different hepatobiliary effects of oral and transdermal estradiol in postmenopausal women. Gastroenterology 100:482–488, 1991Google Scholar
  52. 52.
    Down RHL, Whiting MJ, Watts McKJ, et al.: Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition.Gut 24:253–259, 1983Google Scholar
  53. 53.
    Bennion LJ, Ginsberg RL, Garnick MB, et al.: Effects of oral contraceptives on the gallbladder bile of normal women. N Eng J Med 294:189–192, 1976Google Scholar
  54. 54.
    Kern F Jr, Everson GT, DeMark B, et al.: Biliary lipids, bile acids and gallbladder function in human female: effects of contraceptive steroids. J Lab Clin Med 99:798–805, 1982Google Scholar
  55. 55.
    Kern F Jr, Everson GT: Contraceptive steroids increase cholesterol in bile: Mechanisms of action. J Lipid Res 28:828–837, 1987Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Radha K. Dhiman
    • 1
  • Pralay K. Sarkar
    • 1
  • Arpita Sharma
    • 1
  • Kala Vasishta
    • 2
  • Krishan K. Kohli
    • 3
  • Sanjay Gupta
    • 4
  • Sudha Suri
    • 4
  • Yogesh Chawla
    • 1
  1. 1.Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarh-India
  2. 2.Department of Obstetrics and GynaecologyPostgraduate Institute of Medical Education and ResearchChandigarh-India
  3. 3.Department of BiochemistryPostgraduate Institute of Medical Education and ResearchChandigarh-India
  4. 4.Department of RadiodiagnosisPostgraduate Institute of Medical Education and ResearchChandigarh-India

Personalised recommendations