Association of hormone replacement therapy with mortality in colorectal cancer survivor: A systematic review and meta-analysis

Abstract

Background: Hormone replacement therapy (HRT) use has shown to be associated with a reduced risk of colorectal cancer, however, its impact on survival among women with colorectal cancer remains uncertain. This meta-analysis aimed to systematically assess the survival benefit of HRT use in patients with colorectal cancer. Methods: PRISMA guidelines for the reporting of meta-analyses were followed. We systematically searched PubMed, Embase, Cochrane library, Scopus, and PsycINFO from inception to 12 January 2019, with no language restrictions, for randomized controlled trials and cohort studies reporting the association between hormone replacement therapy and risk of colorectal cancer mortality or all-cause mortality in colorectal cancer survivors. We used the Newcastle-Ottawa Scale to assess the risk of bias of the included studies. We summarized the association as hazard ratio (HR; 95% CI) using random-effects meta-analysis. The study protocol was registered in PROSPERO (CRD42017071914). Results: Of 1648 articles identified, five cohorts including 10,013 colorectal cancer survivors were included in this meta-analysis. Compared with women with no prior use of HRT, those reporting current use of HRT had lower risks of colorectal cancer-specific mortality (HR, 0.71 [95% CI, 0.62-0.80], I 2 = 0%) and overall mortality (HR, 0.74 [95% CI, 0.67-0.81], I 2 = 0%). Low between-study variance was also suggested by the narrow prediction interval for colorectal cancer-specific mortality (0.58-0.86) and overall mortality (0.63-0.87), which indicated that a future study will show survival benefits in women with current HRT use compared with those with no HRT exposure. Inverse associations with colorectal cancer-specific (HR, 1.02 [95% CI, 0.82-1.28], I 2 = 0%) and overall mortality (HR, 1.07 [95% CI, 0.90-1.27], I 2 = 0%) were not observed for former users of HRT. Sensitivity analyses revealed no differences in the risk estimates between two groups. Conclusions: The findings suggest that the current use of HRT is associated with lower risks of colorectal cancer-specific and overall mortality in patients with colorectal cancer. Further investigations to elucidate the underlying mechanism are warranted.