Journal Article:
Wang, S., Wang, Y., Xu, J., & Chen, Y. (2017). Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis: A systematic review and meta-analysis. Medicine, 96(14), e6556
Article Review:
The article begins by explaining that there are major gender difference in prevalence of gallstones (forty, fat, fair, female, fertile), which is presumed to be related to female sex hormones, such as estrogen. Therefore, it makes sense to assume that oral contraceptives and hormone replacement therapy, which contain exogenous estrogen, would increase one’s risk for getting cholelithiasis and ultimately cholecystitis or another biliary event like acute gallstone pancreatitis. The article also argues that while previous studies have been done to assess the relationship between oral contraceptives and HRT’s with the incidence of gallstones, the results over the years have been inconstant, in that some studies showed a positive relationship between the two variables, while others showed no evidence of a significant relationship. The goal of this article is therefore to analyze the previous articles on the topic, and evaluate the association of exogenous estrogen (both oral contraceptiion and HRT) and incidence of gallstones, in order to help provide evidence for further clinical decision-making.
The article performed a meta-analysis, which used studies from PUBMED, EMBASE, and Cochrane databases, up until 2016. Ultimately 19 articles were reviewed, including 9 case-control studies and 10 cohort studies, with a total 21, 476 pts from ages 14-80 years old taking either oral contraceptives or HRT. The study also included some men taking exogenous estrogen for prostate cancer treatment, however most participants were women and focused on oral contraceptives and HRT. Overall, the results of the study found that exogenous estrogen significantly increased the risk of cholelithiasis when all the results were pooled. However, when looking at the relationship of oral contraception and cholelithiasis and then that of HRT and cholelithiasis, individually, it found that this relationship was only significantly positive for HRT, and that oral contraceptives did not actually increase the risk of cholelithiasis. Additionally, there was one study analyzed that proved estrogen was a risk factor for cholelithiasis in males with prostatic cancer; however more studies involving males with prostate cancer receiving taking estrogen would need to be done to determine the significance of this risk.
The article also proposed a few pathophysiological mechanisms behind why estrogen increases risk for gallstones. First, the article explains estrogen impacts lipid metabolism by a receptor called estrogen receptor alpha, which thereby increases the burden on the gallbladder, increasing the risk of gallstones. Second, estrogen can cause relaxation of the gallbladder by binding to G-protein coupled estrogen receptors.
Overall the meta-analysis proved that HRT is a risk factor for cholelithiasis while oral contraception is not. Some limitations of the study include the fact that the oral contraceptive pills were used mainly by young women, while the HRT was used primarily by older women who were postmenopausal. This age difference could be a confounding factor that might play a role in the effects of OCPs versus HRT on gallstone risk, and thereby skew the results of the study.
