Does estrogen replacement therapy increase the risk of gallbladder disease, and is transdermal administration associated with a lower prevalence of gallbladder disease?

Estrogen replacement increases the likelihood of a women being admitted for cholecystectomy. The risk is higher with oral replacement than with transdermal administration. Over 5 years, using transdermal administration instead of oral treatment will prevent one gallbladder removal for every 140 women treated. (LOE = 1b)

Liu B, Beral V, Balkwill A, Green J, Sweetland S, Reeves G, for the Million Women Study Collaborators. Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ 2008;337:a386.  [PMID:18617493]

Cohort (prospective)

Government

Population-based

Oral estrogen replacement therapy is metabolized by the liver, and metabolites are excreted into bile; transdermal administration avoids exposing the gallbladder to such high concentrations. This study is part of an evaluation of more than one million postmenopausal women recruited in England and Scotland who attended breast cancer screening clinics (all women are offered screening after age 50 years). Of these women, 32% used hormone replacement at enrollment, and another 18% had used replacement in the past. All women entered in the study were followed up via National Health Service records. Over an average 6.1 years, 1.7% of the women had a cholecystectomy. Current and past users of hormone replacement were significantly more likely to experience gallbladder disease with the risk being greater in current users than in past users. The risk with transdermal estrogen was less than that with oral equine estrogen (relative risk = 1.17; 95% CI, 1.10 - 1.24 vs 1.74; 1.58 - 1.69). Over 5 years, the use of transdermal estrogen instead of oral therapy would avoid one cholecystectomy in every 140 users (number needed to treat = 140).