Victoria Wocalewski, Giola B. Santoni, Helgi Birgisson, My Catarina von Euler-Chelpin, Joonas H Kauppila, Eivind Ness-Jensen, Shaohua Xie, Jesper Lagergren
BACKGROUND: The incidence of esophago-gastric cancer has an age-dependent male predominance mirroring the physiological sex differences in sex hormonal levels. Some research suggests that menopausal hormone therapy counteracts these tumors to occur, but larger studies with longer follow-up are needed, which prompted this study. METHODS: This population-based case-control study included women aged 45 years and older in the 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) between 1995 and 2020. Prospectively collected data came from national registries for medications, cancer, diagnoses, total populations, and death. Menopausal hormone therapy use was categorized as nonuse (referent) and 3 equal-sized groups (tertiles) of defined daily doses (DDDs). Esophago-gastric cancer was divided into esophageal or cardia adenocarcinoma, esophageal squamous cell carcinoma, and gastric adenocarcinoma. Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for multiple confounders. RESULTS: The study included 19 518 esophago-gastric cancer patients and 195 094 control participants matched for age, calendar year, and country. Compared with nonuse, the adjusted odds ratios of esophageal or cardia adenocarcinoma were 0.74 (95% CI = 0.67 to 0.81) for low menopausal hormone therapy use (<158 DDDs), 0.68 (95% CI = 0.61 to 0.75) for intermediate menopausal hormone therapy use (158-848 DDDs), and 0.68 (95% CI = 0.66 to 0.81) for high menopausal hormone therapy use (>848 DDDs). The corresponding odds ratios were 0.69 (95% CI = 0.62 to 0.77), 0.70 (95% CI = 0.62 to 0.77), and 0.71 (95% CI = 0.64 to 0.79) for esophageal squamous cell carcinoma and 0.90 (95% CI = 0.84 to 0.96), 0.85 (95% CI = 0.79 to 0.91), and 0.80 (95% CI = 0.74 to 0.86) for gastric adenocarcinoma, respectively. CONCLUSION: Menopausal hormone therapy users seem to have lower odds of developing esophago-gastric cancer.