Menopausal Hormone Therapy and Risk of Gallbladder Disease

A Cochrane review [Abstract] 1 included 4 trials comparing hormone therapy (HT) with placebo concerning gallbladder disease. Risk was increased with HT compared to placebo: oestrogen-only HT (RR 1.78, 95% CI 1.42 to 2.24; 3 trials, n=8930); combined continuous HT (RR 1.64, 95% CI1.30 to 2.06; 1 trial, n=14 203).

In a prospective cohort study (Million Women Study) 2 in UK 1 001391 postmenopausal women were recruited at NHS breast screening centres and followed for gallbladder disease. Compared with never users of HT, current users were more likely to be admitted for gallbladder disease but risks were substantially lower with transdermal therapy (RR 1.17, 95% CI 1.10 to 1.24) than with oral therapy (RR 1.74, 95% CI 1.68 to 1.80). Among women using oral therapy, equine oestrogens were associated with a slightly greater risk of gallbladder disease than estradiol (RR 1.79, 95% CI 1.72 to 1.87 vs RR 1.62, 95% CI 1.54 to 1.70) and higher doses of oestrogen increased the risk more than lower doses. The risk of gallbladder disease decreased with time since stopping therapy.

Comment: The certainty of evidence is downgraded by indirectness (only 31% of the study participants were 50 to 59 years of age at baseline (mean participant age was 63 years).

References

• Bofill Rodriguez M, Yong LN, Mirkov S, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2025;11(11):CD004143. [PubMed]
• 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. [PubMed]