Supplement: Table S1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the reporting of meta-analyses. Table S2. Search strategies on the PubMed. Table S3. Search strategies on the Ovid Embase. Table S4. Search strategies on the Cochrane Library. Table S5. Details of combined risk estimates used in Figure 2. Table S6. Details of combined risk estimates used in Figure 4. Table S7. Details of combined risk estimates used in Figure 5. Table S8. List of references with final exclusion reasons. Table S9. Newcastle-Ottawa Quality Assessment Scale for cohort studies. Figure S1. Prediction interval of pancreatic cancer risk for the use of menopausal hormone therapy, using random-effects model. Figure S2. Funnel plot of pancreatic cancer risk
ARTICLE ABSTRACTAlthough menopausal hormone therapy (MHT) is commonly prescribed, little is known about the association between MHT use and risk of pancreatic cancer.
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.
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.
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.
The findings of this study indicate that future investigation should focus on MHT formulations.