Liu B et al. (2008) Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study. BMJ 337: a386

An increased risk of gallbladder disease has previously been shown in postmenopausal women using hormone replacement therapy (HRT). A new study investigating the relationship between method of HRT administration and gallbladder disease risk has now reported an increased risk in postmenopausal women using oral HRT compared with transdermal HRT.

The prospective, cohort study involved 1,001,391 postmenopausal women. Participants were categorized according to HRT use and method of HRT administration at recruitment. During follow-up, 19,889 women had a first hospital admission for gallbladder disease, and 86% of these patients underwent cholecystectomy. Consistent with previous studies, HRT users had an increased risk of gallbladder disease compared with those who had never used HRT. Among past users, risk of gallbladder disease declined with increasing time since last use; however, the risk remained significantly greater than in nonusers, even 10 years after stopping HRT.

Interestingly, the risk of gallbladder disease was found to differ depending on the method of HRT administration; oral therapy conferred a substantially greater risk of gallbladder disease than transdermal therapy. Results were similar for risk of cholecystectomy. Standardized hospital admission rates over 5 years for a cholecystectomy were 1.1% in never users, 1.3% in users of transdermal HRT and 2.0% in users of oral HRT.

The authors speculate that transdermal HRT administration could result in lower bile concentrations of estrogen metabolites, potentially explaining the lower risk of gallbladder disease found in transdermal HRT users compared with oral HRT users. These findings should be taken into consideration when prescribing HRT to postmenopausal women.