Gallbladder disease and use of transdermal versus oral hormone replacement therapy in postmenopausal women: prospective cohort study.

OBJECTIVE: To determine whether transdermal compared with oral use of hormone replacement therapy reduces the risk of gallbladder disease in postmenopausal women. DESIGN: Prospective cohort study (Million Women Study). SETTING: Women registered with the National Health Service (NHS) in England and Scotland. PARTICIPANTS: 1,001,391 postmenopausal women (mean age 56) recruited between 1996 and 2001 from NHS breast screening centres and followed by record linkage to routinely collected NHS hospital admission data for gallbladder disease. MAIN OUTCOME MEASURES: Adjusted relative risk and standardised incidence rates of hospital admission for gallbladder disease or cholecystectomy according to use of hormone replacement therapy. RESULTS: During follow-up 19 889 women were admitted for gallbladder disease; 17 190 (86%) had a cholecystectomy. Compared with never users of hormone replacement therapy, current users were more likely to be admitted for gallbladder disease (relative risk 1.64, 95% confidence interval 1.58 to 1.69) but risks were substantially lower with transdermal therapy than with oral therapy (relative risk 1.17, 1.10 to 1.24 v 1.74, 1.68 to 1.80; heterogeneity P<0.001). Among women using oral therapy, equine oestrogens were associated with a slightly greater risk of gallbladder disease than estradiol (relative risk 1.79, 1.72 to 1.87 v 1.62, 1.54 to 1.70; heterogeneity P<0.001) and higher doses of oestrogen increased the risk more than lower doses: for equine oestrogens >0.625 mg, 1.91 (1.78 to 2.04) v 1 mg, 1.68 (1.59 to 1.77) v