Menopausal hormone therapy and risk of liver cancer in a swedish population-based cohort study.

[BACKGROUND] Previous studies have suggested a potential role of sex hormones in the development of liver cancer. This study aimed to examine whether menopausal hormone therapy (MHT) is associated with a decreased risk of liver cancer by histological type.

[METHOD] This Swedish population-based cohort study included 217,878 women who received MHT in 2006 to 2023 and an age-matched comparison group of 1,089,390 women who did not receive MHT. Cox regression assessed the associations between use of MHT and the risk of two main subtypes of liver cancer, ie, hepatocellular carcinoma and intrahepatic cholangiocarcinoma, with adjustment for smoking- and alcohol-related diagnoses, non-alcoholic fatty liver disease, diabetes or obesity, hysterectomy, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins.

[RESULTS] MHT users had a decreased risk of hepatocellular carcinoma (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29 to 0.70). Decreased HRs of hepatocellular carcinoma were indicated both in users of estrogen only (HR 0.42, 95% CI 0.21 to 0.86) and estrogen combined with progestogen (HR 0.49, 95% CI 0.28 to 0.85). The risk reduction in hepatocellular carcinoma was apparently more pronounced in users aged 60 years or older (HR 0.37, 95% CI 0.19 to 0.75). Use of MHT was not associated with the risk of intrahepatic cholangiocarcinoma (HR 0.99, 95% CI 0.72 to 1.36).

[CONCLUSIONS] MHT in women may decrease the risk of hepatocellular carcinoma, but not intrahepatic cholangiocarcinoma.