Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis: A systematic review and meta-analysis

Medicine (Baltimore). 2017 Apr;96(14):e6556. doi: 10.1097/MD.0000000000006556.


Background: Association between exogenous estrogen intake and cholelithiasis risk has been reported in several epidemiological studies, including oral contraceptive (OC) and hormone replacement therapy (HRT), while the results were controversial. This study aimed to perform a comprehensive meta-analysis of this issue.

Methods: PUBMED, EMBASE, and Cochrane library database were searched up to October 2016. Two reviewers independently extracted data from eligible studies, relative risks (RRs), and/or odds ratios (ORs) with 95% confidence intervals (95% CIs) for the highest versus lowest categories of intake were adopted. Either a fixed- or a random-effects model was adopted to estimate overall RRs or ORs. Besides, subgroup and publication bias analyses were applied to explain the heterogeneity. An original study was also conducted to verify our conclusion.

Results: A total of 19 studies with approximately 556,620 participants were included in this meta-analysis. The pooled RR of cholelithiasis for the highest versus the lowest categories was 1.59 (95% CI: 1.44-1.75), indicating that exogenous estrogen was positive associated with the intake of exogenous estrogen. However, the pooled RR of OC intake and cholelithiasis risk was 1.19 (95% CI: 0.97-1.45), and the RR for HRT was 1.79 (95% CI: 1.61-2.00).

Conclusion: The HRT was positively associated with the cholelithiasis risk, and the OC will not increase the risk of cholelithiasis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Contraceptives, Oral, Hormonal / adverse effects*
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogens / administration & dosage
  • Estrogens / adverse effects*
  • Female
  • Gallstones / chemically induced*
  • Humans


  • Contraceptives, Oral, Hormonal
  • Estrogens