Comparison of the Impact of Transdermal Versus Oral Estrogens on Biliary Markers of Gallstone Formation in Postmenopausal Women

Uhler, M.L.; Marks, Jay W.; Voigt, Barbara; Judd, Howard L.

doi:10.1097/00006254-199806000-00018

Cited by 11 publications

(17 citation statements)

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“…The bile becomes more saturated with cholesterol resulting in a rise of the CSI and in an increased risk for cholesterol crystal formation. This has been shown especially for hormone replacement therapy in postmenopausal women and in men receiving estrogen therapy [54,60]. But also during pregnancy cholesterol secretion increases in relation to bile acid and phospholipid secretion resulting in cholesterol supersaturation of bile.…”

Section: Female Gender Pregnancy and Estrogen Therapy As Risk Factormentioning

confidence: 96%

“…A randomized trial for secondary prevention of coronary heart disease in postmenopausal women revealed that women in the hormone group (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate) were at increased risk of gallbladder disease compared to women in the placebo group during an average follow-up of 4 years (relative hazard 1.38; 95 % CI 1.00-1.92) [52]. Recently published data from the Women's Health Initiative, which consisted of two randomized placebo-controlled trials comparing estrogen or estrogen plus progestin in postmenopausal women with and without hysterectomy, respectively, suggested a significantly increased risk for biliary tract disease among those women using estrogen therapy [53]: Both trials showed a greater risk of any gallbladder disease or surgery (estrogen alone: hazard ratio (HR) 1 Despite the assumption that transdermal administration of estrogen may reduce the impact of this hormone on gallstone formation, estrogens seem to alter the bile to more lithogenic, whether administered transcutaneously or orally [54].…”

Section: Female Gender Pregnancy and Estrogen Therapy As Risk Factormentioning

confidence: 99%

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Gender and Gallstone Disease

Novacek

2006

Wien Med Wochenschr

124

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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.

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Section: Female Gender Pregnancy and Estrogen Therapy As Risk Factormentioning

confidence: 96%

Section: Female Gender Pregnancy and Estrogen Therapy As Risk Factormentioning

confidence: 99%

Gender and Gallstone Disease

Novacek

2006

Wien Med Wochenschr

124

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“…Accumulated evidence from clinical studies has found that the use of oral contraceptive steroids and conjugated estrogens in premenopausal women significantly enhances the formation of cholesterol gallstones [22–25]. Furthermore, estrogen therapy to postmenopausal women and to men with prostatic carcinoma induces similar lithogenic effects [26–31]. These observations support the concept that higher risks for cholesterol gallstones in women than in men are related to differences in how the liver handles cholesterol in response to estrogen [1].…”

Section: Introductionmentioning

confidence: 99%

New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation

Wang

Liu

Clegg

et al. 2009

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

109

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Epidemiological and clinical studies have found that at all ages women are twice as likely as men to form cholesterol gallstones, and this gender difference begins since puberty and continues through the childbearing years, which highlight the importance of female sex hormones. Estrogen is a crucial hormone in human physiology and regulates a multitude of biological processes. The actions of estrogen have traditionally been ascribed to two closely related classical nuclear hormone receptors, estrogen receptor 1 (ESR1) and ESR2. Recent studies have revealed that the increased risk for cholesterol gallstones in women vs. men is related to differences in how the liver metabolizes cholesterol in response to estrogen. A large number of human and animal studies have proposed that estrogen increases the risk of developing cholesterol gallstones by increasing the hepatic secretion of biliary cholesterol, which, in turn, leads to an increase in cholesterol saturation of bile. Furthermore, it has been identified that hepatic ESR1, but not ESR2, plays a major role in cholesterol gallstone formation in mice in response to high doses of 17β-estradiol. The mechanisms mediating estrogen’s action has become more complicated with the recent identification of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), a member of the seven-transmembrane G protein-coupled receptor superfamily. In this review, we provide an overview of the evidence for the lithogenic actions of estrogen through ESR1 and discuss the cellular and physiological actions of GPR30 in estrogen-dependent processes and the relationship between GPR30 and classical ESR1 on gallstone formation.

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“…Offenbar bewirken konjugierte equine Östrogene eine Hemmung der Gallensäuresynthese; auch transdermales Östradiol kann Veränderungen induzieren, die einer Gallensteinbildung Vorschub leisten [81].…”

Section: Gallenblasenerkrankungenunclassified