Effect of estrogen therapy on gallbladder disease

Dominic J. Cirillo, Robert B. Wallace*, Rebecca J. Rodabough, Philip Greenland, Andrea Z. LaCroix, Marian C. Limacher, Joseph C. Larson

*Corresponding author for this work

Research output: Contribution to journalArticle

172 Scopus citations

Abstract

Context: Estrogen therapy is thought to promote gallstone formation and cholecystitis but most data derive from observational studies rather than randomized trials. Objective: To determine the effect of estrogen therapy in healthy postmenopausal women on gallbladder disease outcomes. Design, Setting, and Participants: Two randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers. The volunteer sample was 22579 community-dwelling women aged 50 to 79 years without prior cholecystectomy. Intervention: Women with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203). Main Outcome Measures: Participants reported hospitalizations for gallbladder diseases and gallbladder-related procedures, with events ascertained through medical record review. Cox proportional hazards regression was used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) using intention-to-treat and time-to-event methods. Results: The CEE and the E+P groups were similar to their respective placebo groups at baseline. The mean follow-up times were 7.1 years and 5.6 years for the CEE and the E+P trials, respectively. The annual incidence rate for any gallbladder event was 78 events per 10000 person-years for the CEE group (vs 47/10000 person-years for placebo) and 55 per 10000 person-years for E+P (vs 35/10000 person-years for placebo). Both trials showed greater risk of any gallbladder disease or surgery with estrogen (CEE: HR, 1.67; 95% CI, 1.35-2.06; E+P: HR, 1.59; 95% CI, 1.28-1.97). Both trials indicated a higher risk for cholecystitis (CEE: HR, 1.80; 95% CI, 1.42-2.28; E+P: HR, 1.54; 95% CI 1.22-1.94); and for cholelithiasis (CEE: HR, 1.86; 95% CI, 1.48-2.35; E+P: HR, 1.68; 95% CI, 1.34-2.11) for estrogen users. Also, women undergoing estrogen therapy were more likely to receive cholecystectomy (CEE: HR, 1.93; 95% CI, 1.52-2.44; E+P: HR, 1.67; 95% CI, 1.32-2.11), but not other biliary tract surgery (CEE: HR, 1.18; 95% CI, 0.68-2.04; E+P: HR, 1.49; 95% CI, 0.78-2.84). Conclusions: These data suggest an increase in risk of biliary tract disease among postmenopausal women using estrogen therapy. The morbidity and cost associated with these outcomes may need to be considered in decisions regarding the use of estrogen therapy.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalJournal of the American Medical Association
Volume293
Issue number3
DOIs
StatePublished - Jan 19 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Cirillo, D. J., Wallace, R. B., Rodabough, R. J., Greenland, P., LaCroix, A. Z., Limacher, M. C., & Larson, J. C. (2005). Effect of estrogen therapy on gallbladder disease. Journal of the American Medical Association, 293(3), 330-339. https://doi.org/10.1001/jama.293.3.330