HRT associated with cholelithiasis risk
Hormone replacement therapy (HRT), but not oral contraceptives (OC), could lead to the development of gallstones, a recent study has found.
In this meta-analysis, exogenous oestrogen intake was associated with risk of cholelithiasis (pooled risk ratio [RR], 1.59, 95 percent confidence interval [CI], 1.44–1.75). [Medicine (Baltimore) 2017;96:e6556]
However, on subgroup analysis, risk of cholelithiasis was significantly associated with HRT (pooled RR, 1.79, 95 percent CI, 1.61–2.00) but not with OC (pooled RR, 1.19, 95 percent CI, 0.97–1.45).
“[Our study] indicates that OC is not the risk factor for cholelithiasis, which will be beneficial to eliminate the bias for the OC. As for the HRT, our results proved it can significantly increase the incidence of cholelithiasis,” said the researchers.
Results from the researchers’ original study conducted on a postmenopausal Chinese female population further support these findings, which revealed a high risk of cholelithiasis with HRT (RR, 2.01, 95 percent CI, 1.43–2.83 for <2 years and RR, 1.78, 95 percent CI, 1.02–3.60 for ≥2 years) and OC intake (RR, 1.23, 95 percent CI, 0.90–1.68 for <1 year and RR, 1.52, 95 percent CI, 0.64–3.60 for ≥1 year).
Previous studies evaluating the molecular mechanism of oestrogen in the bile duct and gall bladder revealed G protein-coupled receptor 30 and oestrogen receptor α as influential in lipid metabolism, which could increase the likelihood of gallstone formation. [Biochim Biophys Acta 2015;1852:2161-2169; Gastroenterology 2015;148:S295; J Lipid Res 2015;56:1691-700]
Researchers evaluated 19 studies comprising participants aged 14–80 years who were on OC or HRT. Of note is one study that reported oestrogen use in males with prostate cancer, implying that oestrogen could also be a potential risk factor for gallstones in the male population. [J Clin Invest 1989;84:811-816] Further studies are warranted to verify this theory, noted the researchers.
Exogenous oestrogen has been associated with more serious cancer risks (eg, breast, ovarian, endometrial), but its effect on gallstone formation has not been extensively studied. Furthermore, previous studies have shown both positive and negative associations between gallstone formation and HRT and OC intake. [Drug Saf 2013;36:1189-1197; JAMA 2005;293:330-339; Scand J Gastroenterol 2014;49:109-113; Ann Intern Med 2001;135:493-501]
Therefore, it is important to establish a definitive link between cholelithiasis and oestrogen therapy to help clinicians in the management of gallstones, said the researchers, adding that this could raise awareness for overweight women under exogenous oestrogen therapy.