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:1001391 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 P0.625 mg, 1.91 (1.78 to 2.04) v ≤0.625 mg, 1.76 (1.68 to 1.84); heterogeneity P=0.02; estradiol >1 mg, 1.68 (1.59 to 1.77) v ≤1 mg, 1.44 (1.31 to 1.59); heterogeneity P=0.003. The risk of gallbladder disease decreased with time since stopping therapy (trend P=0.004). Results were similar taking cholecystectomy as the outcome. Standardised hospital admission rates per 100 women over five years for cholecystectomy were 1.1 in never users, 1.3 with transdermal therapy, and 2.0 with oral therapy. CONCLUSION: Gallbladder disease is common in postmenopausal women and use of hormone replacement therapy increases the risk. Use of transdermal therapy rather than oral therapy over a five year period could avoid one cholecystectomy in every 140 users.This work was supported by Cancer Research UK [grant No C570/A5028], the NHS breast screening programme, and the UK Medical Research Council [grant No G0700474]