Association of Menopausal Hormone Therapy with Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis of Cohort Studies

Background: Although menopausal hormone therapy (MHT) is commonly prescribed, little is known about the association between MHT use and risk of pancreatic cancer.Methods: We searched PubMed, Embase, and Cochrane Library, from inception until April 20, 2022. The risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale. Pooled rel-ative risks (RR) for pancreatic cancer risk were calculated using random-effects models. We computed prediction intervals (PI) and performed subgroup meta-analyses. Meta-regression was per-formed to investigate the sources of heterogeneity.Results: This study included 2,712,313 women from 11 cohort studies. There was no association between MHT and pancreatic cancer risk (RR, 0.92; 95% confidence interval (CI), 0.83-1.02; I2, 64%; 95% PI, 0.68-1.25). Subgroup meta-analyses of four studies stratified by MHT formulations showed inverse associations with the risk of pancreatic cancer (women receiving estrogen-only MHT: RR, 0.77; 95% CI, 0.64-0.94; I2, 57%; estrogen plus progestin MHT: RR, 0.85; 95% CI, 0.75-0.96; I2, 0%). Subgroup analysis defined by recency and duration of treatment did not reveal evidence of associations between MHT and pancreatic cancer risk.Conclusions: This study found no association between the over-all use of MHT and risk of pancreatic cancer. However, among four studies with data on MHT formulations, subgroup analysis showed a decreased risk of pancreatic cancer among users of estrogen-only and combined estrogen-progestin therapy. Owing to the inconsis-tent findings between our main and subgroup analyses, future studies stratified by MHT formulations are warranted.Impact: The findings of this study indicate that future investi-gation should focus on MHT formulations.

Automated summary

Analysis of 11 cohort studies involving 2,712,313 women found no overall association between menopausal hormone therapy (MHT) use and risk of pancreatic cancer. However, subgroup analysis revealed a decreased risk among users of estrogen-only and combined estrogen-progestin therapy. Future studies should focus on investigating MHT formulations.