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 relative 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 performed 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; I(2), 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; I(2), 57%; estrogen plus progestin MHT: RR, 0.85; 95% CI, 0.75–0.96; I(2), 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 overall 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 inconsistent findings between our main and subgroup analyses, future studies stratified by MHT formulations are warranted. IMPACT: The findings of this study indicate that future investigation should focus on MHT formulations.