Impact of hormone replacement therapy on all-cause and cancer-specific mortality in colorectal cancer: A systematic review and dose‒response meta-analysis of observational studies.

Objective: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all-cause mortality remains unclear. We conducted a systematic review and dose-response meta-analysis to determine the effects of HRT on CRC mortality and all-cause mortality.

Methods: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two-stage random-effects dose-response meta-analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality.

Results: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all-cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I = 89.6%, p < 0.05). A linear dose-response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose-response analysis showed a nonsignificant decrease in the risk of all-cause mortality for each additional year of HRT use.

Conclusions: This study suggests that the use of HRT is inversely associated with all-cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association.