Hormone replacement therapy and gallstone disease: a real association.


that oral estrogen use is causally associated with gallbladder disease, and the magnitude of effect is not influenced greatly by the presence or absence of progestins [5, 6] . Yet another study by Hart et al. [7] from the UK also confirms previous reports that the use of HRT is positively associated with an increased risk of symptomatic gallstones. This first European study also shows that the risk of gallstones appeared greater with an increasing duration of use of HRT. The strengths of this study include the fact that it was a properly conducted investigation with radiological and/ or surgical/pathological confirmation of gallstones, appropriate exclusions and selection of age-matched controls. Despite these advantages, the study has several weaknesses/limitations as also discussed by the authors. The study is unable to provide an answer on the effect of dose of estrogen on occurrence of symptomatic gallstones. The results of the study apply only to symptomatic gallstones but not to the clinically silent gallstones. It is also not clear whether HRT influences the natural history of clinically silent gallstones by making them symptomatic. Estrogen use has been shown to cause inflammation or pain or both, thus resulting in an intensification of symptoms [1, 8, 9] . The same mechanism can cause clinically silent gallstones to become symptomatic. However, this issue needs to be examined prospectively by performing abdominal ultrasonography of the subjects at the time of inclusion into the study. Though there are no ethical issues with ultrasound examination in Cholelithiasis is the most common form of benign gallbladder disease. Cholesterol gallstones occur more frequently in women than in men in all parts of the world. The role of female sex hormones in the pathogenesis of gallstones is well established [1] . The sex difference starts at puberty, continues throughout the fertile period and diminishes after menopause [1] . Observational studies indicate a 2to 4-fold increased risk for gallbladder disease related to estrogen therapy ( table 1 ). The Nurses’ Health study found an increased risk of cholecystectomies among participants taking postmenopausal hormones, with a relative risk (RR) of 2.1 for current hormone users. Higher risks were associated with longer duration of use (RR 1.4 and RR 1.7 for past users of ! 2 years and 6 10 years’ duration, respectively) and higher doses (RR 1.3 for users of 0.3 mg daily of estrogen compared to RR of 2.4 for users of 1.25 mg or more daily) [2] . Mamdami et al. [3] also reported an increased risk of cholecystectomies among Canadian women who recently started using estrogen. The Atherosclerosis Risk in Communities (ARIC) study group also demonstrated that both current and former users of hormone replacement therapy (HRT) had a significantly increased risk of gallbladder disease [4] . Two recently conducted randomized controlled trials among women that examined gallbladder disease outcome after HRT – the Heart and Oestrogen/Progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) Postmenopausal Hormone Trial – also unequivocally confirmed Published online: January 21, 2008

DOI: 10.1159/000113896

1 Figure or Table

Cite this paper

@article{Dhiman2008HormoneRT, title={Hormone replacement therapy and gallstone disease: a real association.}, author={Radha Krishan Dhiman and Yogesh Kumar Chawla}, journal={Digestion}, year={2008}, volume={77 1}, pages={1-3} }