Skip to main content
SpringerLink
Log in

Gender and Gallstone Disease

Gender und Gallensteine

  • Themenschwerpunkt
  • Published:
Wiener Medizinische Wochenschrift Aims and scope Submit manuscript

Zusammenfassung

Gallensteine zählen weltweit zu den häufigsten Erkrankungen. In den westlichen Ländern sind etwa 80 % der Gallensteine Cholesterinsteine. Für die Gallensteinbildung sind einige Risikofaktoren bekannt. Zu den wichtigsten zählt das weibliche Geschlecht. Frauen haben gegenüber Männern ein 2- bis 3-fach erhöhtes Risiko für Gallensteine, das jedoch hauptsächlich auf das gebärfähige Alter beschränkt ist. Ein weiterer Risikofaktor sind Schwangerschaften, wobei das Risiko mit der Anzahl der Schwangerschaften ansteigt. Für das erhöhte Gallensteinrisiko sind weibliche Sexualhormone verantwortlich. Östrogen bewirkt eine vermehrte Cholesterinsekretion in die Galle und steigert dadurch die Cholesterinsättigung. Daher sind auch Hormonersatztherapien für Frauen in der Menopause und orale Kontrazeptive mit einem erhöhten Risiko für Gallensteine verbunden. Da jedoch der Effekt von Östrogen dosisabhängig ist, kann für neuere orale Kontrazeptive mit niedriger Östrogendosis das erhöhte Risiko nicht mehr nachgewiesen werden. Im Mittelpunkt des vorliegenden Artikels stehen die genannten, mit weiblichen Sexualhormonen assoziierten Risikofaktoren für die Gallensteinbildung.

Summary

Gallstone disease is a common disorder all over the world. In the Western societies about 80 % of the gallstones are composed primarily of cholesterol. Several risk factors for gallstone formation have been identified. One of the most important risk factors is female gender. Rates of gallstones are two to three times higher among women than men. But this is primarily a phenomenon of the childbearing age. Pregnancy is also a major risk factor for gallstone formation. The risk is related to the number of pregnancies. Sex hormones are most likely to be responsible for the increased risk. Estrogen increases biliary cholesterol secretion causing cholesterol supersaturation of bile. Thus, hormone replacement therapy in postmenopausal women and oral contraceptives have also been described to be associated with an increased risk for gallstone disease. However, the effect of estrogen is dose-dependent and new oral contraceptives with a low estrogen dose do not seem to increase the rate of gallstone formation. The present article focuses on the mentioned risk factors associated with female sex hormones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Barbara L, Sama C, Labate AMM, Taroni F, Rusticali AG, Festi D, Sapio C, Roda E, Banterle C, Puci A, Formentini F, Colasanti S, Nardin F (1987) A population study on the prevalence of gallstone disease: the Sirmione study. Hepatology 7: 913–917

    PubMed  CAS  Google Scholar 

  • Glambek I, Kvaale G, Arnesjö B, Søreide O (1987) Prevalence of gallstones in Norwegian population. Scand J Gastroenterol 22: 1089–1094

    PubMed  CAS  Google Scholar 

  • Jørgensen T (1987) Prevalence of gallstones in a Danish population. Am J Epidemiol 126: 912–921

    PubMed  Google Scholar 

  • Kratzer W, Kron M, Hay B, Pfeiffer MM, Kächele V (1999) Prävalenz der Cholezystolithiasis in Süddeutschland – eine sonographische Untersuchung an 2.498 Personen einer ländlichen Bevölkerung. Z Gastroenterol 37: 1157–1162

    PubMed  CAS  Google Scholar 

  • Volzke H, Baumeister SE, Alte D, Hoffmann W, Schwahn C, Simon P, John U, Lerch MM (2005) Independent risk factors for gallstone formation in a region with high cholelithiasis prevalence. Digestion 71: 97–105

    Article  PubMed  Google Scholar 

  • Maurer KR, Everhart JE, Ezzati TM, Johannes RS, Knowler WC, Larson DL, Sanders R, Shawker TH, Roth HP (1989) Prevalence of gallstone disease in Hispanic populations in the United States. Gastroenterology 96: 487–492

    PubMed  CAS  Google Scholar 

  • Sampliner RE, Bennett PH, Comess LJ, Rose FA, Burch TA (1970) Gallbladder disease in Pima Indians. Demonstration of high prevalence and early onset by cholecystography. N Engl J Med 283: 1358–1364

    Article  PubMed  CAS  Google Scholar 

  • Williams CN, Johnston JL, Weldon KL (1977) Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women. Can Med Assoc J 117: 758–760

    PubMed  CAS  Google Scholar 

  • Kratzer W, Mason RA, Kächele V (1999) Prevalence of gallstones in sonographic surveys worldwide. J Clin Ultrasound 27: 1–7

    Article  PubMed  CAS  Google Scholar 

  • Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Ikematsu H, Noguchi A, Tani S, Goto M (1988) Prevalence of gallstone disease in a general population of Okinawa, Japan. Am J Epidemiol 128: 598–605

    PubMed  CAS  Google Scholar 

  • Jensen KH, Jørgensen T (1991) Incidence of gallstones in a Danish population. Gastroenterology 100: 790–794

    PubMed  CAS  Google Scholar 

  • Small DM (1976) The etiology and pathogenesis of gallstones. Adv Surg 10: 63–85

    PubMed  CAS  Google Scholar 

  • Kurtin WE, Schwesinger WH, Diehl AK (2000) Age-related changes in the chemical composition of gallstones. Int J Surg Investig 2: 299–307

    PubMed  CAS  Google Scholar 

  • Horton JD, Bilhartz LE (2002) Gallstone disease and its complications. In: Feldman M, Friedman LS, Sleisenger MH (eds.) Sleisenger and Fordtran's gastrointestinal and liver disease, 7th edition. Saunders, Philadelphia, pp 1065–1090

    Google Scholar 

  • Donovan JM, Carey MC (1990) Separation and quantitation of cholesterol "carriers" in bile. Hepatology 12: 94S–104S

    PubMed  CAS  Google Scholar 

  • Lamont JT, Carey MC (1992) Cholesterol gallstone formation. 2. Pathobiology and pathomechanics. Prog Liver Dis 10: 165–191

    PubMed  CAS  Google Scholar 

  • Carey MC, Small DM (1978) The physical chemistry of cholesterol solubility in bile: Relationship to gallstone formation and dissolution in man. J Clin Invest 61: 998–1026

    PubMed  CAS  Google Scholar 

  • Miquel JF, Nunez L, Amigo L, Gonzalez S, Raddatz A, Rigotti A, Nervi F (1998) Cholesterol saturation, not proteins or cholecystitis, is critical for crystal formation in human gallbladder bile. Gastroenterology 114: 1016–1023

    Article  PubMed  CAS  Google Scholar 

  • Brown MS, Goldstein JL (1976) Receptor-mediated control of cholesterol metabolism. Science 191: 150–154

    Article  PubMed  CAS  Google Scholar 

  • Holan KR, Holzbach RT, Hermann RE, Cooperman AM, Claffey WJ (1979) Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology 77: 611–617

    PubMed  CAS  Google Scholar 

  • Sedaghat A, Grundy SM (1980) Cholesterol crystals and the formation of cholesterol gallstones. N Engl J Med 302: 1274–1277

    Article  PubMed  CAS  Google Scholar 

  • Marks JW, Broomfield P, Bonorris GG, Schoenfield LJ (1991) Factors affecting the measurement of cholesterol nucleation in human gallbladder and duodenal bile. Gastroenterology 101: 214–219

    PubMed  CAS  Google Scholar 

  • Lee SP, Lamont JT, Carey MC (1981) The role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones: studies in the prairie dog. J Clin Invest 67: 1712–1723

    PubMed  CAS  Google Scholar 

  • Gallinger S, Taylor RD, Harvey PR, Petrunka CN, Strasberg SM (1985) Effect of mucous glycoprotein on nucleation time in human bile. Gastroenterology 98: 648–658

    Google Scholar 

  • Van Erpecum KJ, Portincasa P, Dohlu MH, Van Berge-Henegouwen GP, Jüngst D (2003) Biliary pronucleating proteins and apolipoprotein E in cholesterol and pigment stone patients. J Hepatol 39: 7–11

    Article  PubMed  CAS  Google Scholar 

  • Smith BF (1987) Human gallbladder mucin binds biliary lipids and promotes cholesterol crystal nucleation in model bile. J Lipid Res 28: 1088–1097

    PubMed  CAS  Google Scholar 

  • Afdhal NH, Niu N, Nunes DP, Bansil R, Cao XX, Gantz D, Small DM, Offner GD (1995) Mucin-vesicle interactions in model bile: evidence for vesicle aggregation and fusion before cholesterol crystal formation. Hepatology 22: 856–865

    Article  PubMed  CAS  Google Scholar 

  • Wood JR, Svanvik J (1983) Gall-bladder water and electrolyte transport and its regulation. Gut 24: 579–593

    PubMed  CAS  Google Scholar 

  • Ko CW, Sekijima JH, Lee SP (1999) Biliary sludge. Ann Intern Med 130: 301–311

    PubMed  CAS  Google Scholar 

  • Lee SP, Maher K, Nicholls JF (1988) Origin and fate of biliary sludge. Gastroenterology 94: 170–176

    PubMed  CAS  Google Scholar 

  • Cetta F (1991) The role of bacteria in pigment gallstone disease. Ann Surg 213: 315–326

    Article  PubMed  CAS  Google Scholar 

  • Stewart L, Oesterle AL, Erdan I, Griffiss JM, Way LW (2002) Pathogenesis of pigment gallstones in Western societies: the central role of bacteria. J Gastrointest Surg 6: 891–903

    Article  PubMed  Google Scholar 

  • Gracie WA, Ransohoff DF (1982) The natural history of silent gallstones: the innocent gallstone is not a myth. N Engl J Med 307: 798–800

    Article  PubMed  CAS  Google Scholar 

  • Attili AF, De Santis A, Capri R, Repice AM, Maselli S, and the GREPCO Group (1995) The natural history of gallstones: the GREPCO experience. Hepatology 21: 656–660

    Article  Google Scholar 

  • Halldestam I, Enell EL, Kullman E, Borch K (2004) Development of symptoms and complications in individuals with asymptomatic gallstones. Br J Surg 91: 734–738

    Article  PubMed  CAS  Google Scholar 

  • Thistle JL, Cleary PA, Lachin JM, Tyor MP, Hersh T (1984) The natural history of cholelithiasis: the National Cooperative Gallstone Study. Ann Internal Med 101: 171–175

    CAS  Google Scholar 

  • Houdart R, Perniceni T, Darne B, Salmeron M, Simon JF (1995) Predicting common bile duct lithiasis: determination and prospective validation of a model predicting low risk. Am J Surg 170: 38–43

    Article  PubMed  CAS  Google Scholar 

  • Ott DJ, Gilliam JH 3rd, Zagoria RJ, Young GP (1992) Interventional endoscopy of the biliary and pancreatic ducts: current indications and methods. Am J Roentgenol 158: 243–250

    CAS  Google Scholar 

  • Fulcher AS (2002) MRCP and ERCP in the diagnosis of common bile duct stones. Gastrointest Endosc 56: S178–S182

    Article  PubMed  Google Scholar 

  • Moon JH, Cho YD, Cha SW, Cheon YK, Ahn HC, Kim YS, Kim YS, Lee JS, Lee MS, Lee HK, Shim CS, Kim BS (2005) The detection of bile duct stones in suspected biliary pancreatitis: comparison of MRCP, ERCP, and intraductal US. Am J Gastroenterol 100: 1051–1057

    Article  PubMed  Google Scholar 

  • Hochwalk SN, Dobryansky MBA, Rofsky NM, Naik KS, Shamamian P, Coppa G, Marcus SG (1998) Magnetic resonance cholangiopancreatography accurately predicts the presence or absence of choledocholithiasis. J Gastrointest Surg 2: 573–579

    Article  PubMed  CAS  Google Scholar 

  • Sivak MV Jr (2002) EUS for bile duct stones: how does it compare with ERCP? Gastrointest Endosc 56: S175–S177

    Article  PubMed  Google Scholar 

  • Valdivieso V, Covarrubias C, Siegel F, Cruz F (1993) Pregnancy and cholelithiasis: pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology 17: 159–161

    Article  Google Scholar 

  • Katsika D, Grjibovski A, Einarsson C, Lammert F, Lichtenstein P, Marschall HU (2005) Genetic and environmental influences on symptomatic gallstone disease: a Swedish study of 43,141 twin pairs. Hepatology 41: 1138–1143

    Article  PubMed  CAS  Google Scholar 

  • Stampfer MJ, Maclure KM, Colditz GA, Manson JE, Willett WC (1992) Risk of symptomatic gallstones in women with severe obesity. Am J Clin Nutr 55: 652–658

    PubMed  CAS  Google Scholar 

  • Attili AF, Capocaccia R, Carulli N, Festi D, Roda E, Barbara L, Capocaccia L, Menotti A, Okolicsanyi L, Ricci G, Lalloni L, Mariotti S, Sama C, Scafato E, and the MICOL Group (1997) Factors associated with gallstone disease in the MICOL experience. Hepatology 26: 809–818

    Article  PubMed  CAS  Google Scholar 

  • Shiffman ML, Sugerman HJ, Kellum JM, Brewer WH, Moore EW (1991) Gallstone formation after rapid weight loss: A propective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 86: 1000–1005

    PubMed  CAS  Google Scholar 

  • De Santis A, Attili AF, Corradini GS, Scafato E, Cantagalli A, De Luca C, Pinto G, Lisi D, Capocaccia L (1997) Gallstones and diabetes: a case-control study in a free-living population sample. Hepatology 25: 787–790

    Article  PubMed  CAS  Google Scholar 

  • Lapidus A, Bangstad M, Astrom M, Muhrbeck O (1999) The prevalence of gallstone disease in a defined cohort of patients with Crohn's disease. Am J Gastroenterol 94: 1261–1266

    Article  PubMed  CAS  Google Scholar 

  • Uhler M, Marks JW, Judd HL (2000) Estrogen replacement therapy and gallbladder disease in postmenopausal women. Menopause 7: 162–167

    Article  PubMed  CAS  Google Scholar 

  • Grodstein F, Colditz GA, Stampfer MJ (1994) Postmenopausal hormone use and cholecystectomy in a large prospective study. Obstet Gynecol 83: 5–11

    PubMed  CAS  Google Scholar 

  • Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E (1998) Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280: 605–613

    Article  PubMed  CAS  Google Scholar 

  • Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix A, Limacher MC, Larson JC (2005) Effect of estrogen therapy on gallbladder disease. JAMA 293: 330–339

    Article  PubMed  CAS  Google Scholar 

  • Uhler ML, Marks JW, Voigt BJ, Judd HL (1998) Comparison of the impact of transdermal versus oral estrogen on biliary markers. J Clin Endocrinol Metab 83: 410–414

    Article  PubMed  CAS  Google Scholar 

  • Scragg RKR, McMichael AJ, Seamark RF (1984) Oral concraceptives, pregnancy, and endogenous oestrogen in gall stone disease – a case control study. BMJ 288: 1795–1799

    PubMed  CAS  Google Scholar 

  • Strom BL, Tamragouri RN, Morse ML, Lazar EL, West SL, Stolley PD, Jones JK (1986) Oral contraceptives and other risk factors for gallbladder disease. Clin Pharmacol Ther 39: 335–341

    Article  PubMed  CAS  Google Scholar 

  • Thijs C, Leffers P, Knipschild P (1993) Oral contraceptive use and the occurrence of gallstone disease – a case-control study. Prev Med 22: 12–31

    Article  Google Scholar 

  • Thijs C, Knipschild P (1993) Oral contraceptives and the risk of gallbladder disease: a meta-analysis. Am J Public Health 83: 1113–1120

    Article  PubMed  CAS  Google Scholar 

  • Misciagna G, Leoci C, Guerra V, Chiloiro M, Elba S, Petruzzi J, Mossa A, Noviello MR, Coviello A, Minutolo MC, Mangini V, Messa C, Cavallini A, De Michele G, Giogio I (1996) Epidemiology of cholelithiasis in southern Italy. Part II: risk factors. Eur J Gastroenterol Hepatol 8: 585–593

    PubMed  CAS  Google Scholar 

  • Henriksson P, Einarsson K, Eriksson A, Kelter U, Angelin B (1989) 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

    Article  PubMed  CAS  Google Scholar 

  • Maringhini A, Ciambra M, Baccelliere P, Raimondo M, Orlando A, Tinè F, Grasso R, Randazzo MA, Barresi L, Gullo D, Musicò M, Pagliaro (1993) Biliary sludge and gallstones in pregnancy: incidence, risk factors, and natural history. Ann Intern Med 119: 116–120

    PubMed  CAS  Google Scholar 

  • Ko CW, Beresford SA, Schulte SJ, Matsumoto AM, Lee SP (2005) Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology 41: 359–365

    Article  PubMed  Google Scholar 

  • Wang HH, Afdhal NH, Wang DQH (2004) Estrogen receptor α, but not β, plays a major role in 17β-estradiol-induced murine cholesterol gallstones. Gastroenterology 127: 239–249

    Article  PubMed  CAS  Google Scholar 

  • Kern F Jr, Everson GT, DeMark B, McKinley C, Showalter R, Erfling W, Braverman DZ, Szczepanik-vanLeeuwen P, Klein PD (1981) Biliary lipids, bile acids, and gallbladder function in the human female. Effects of pregnancy and the ovulatory cycle. J Clin Invest 68: 1229–1242

    PubMed  CAS  Google Scholar 

  • Van Bodegraven AA, Bohmer CJ, Manoliu RA, Paalman E, Van der Klis AH, Roex AJ, Kruishoop AM, Deville WL, Lourens J (1998) Gallbladder contents and fasting gallbladder volumes during and after pregnancy. Scand J Gastroenterol 33: 993–997

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

    Gottfried Novacek

Authors
  1. Gottfried Novacek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gottfried Novacek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Novacek, G. Gender and Gallstone Disease. Wien Med Wochenschr 156, 527–533 (2006). https://doi.org/10.1007/s10354-006-0346-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10354-006-0346-x

Schlüsselwörter

Keywords

Search

Navigation