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

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.

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 2 main subtypes of liver cancer, that is, 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.

MHT users had a decreased risk of hepatocellular carcinoma (hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.30 to 0.72). 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). The use of MHT was not associated with the risk of intrahepatic cholangiocarcinoma (HR = 0.99, 95% CI = 0.72 to 1.36).

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