Nationwide cohort study of association of tibolone use with hepatocellular carcinoma risk in South Korea

Tibolone, a synthetic steroid with estrogenic, progestogenic, and androgenic activity, is widely prescribed for menopausal symptoms. Its association with hepatocellular carcinoma (HCC) is not clear. A nationwide study using data from 117,271 women aged ≥ 45 years in the Korean National Health Insurance Service-Health Screening Cohort, evaluated tibolone use between 2003 and 2007 and identified incident HCC from 2009 through 2019, implementing a 1-year lag period. Participants were propensity score-matched (1:10) by demographic, lifestyle, and metabolic factors. During a median 11-year follow-up, women with ≥ 180 cumulative days of tibolone use showed a higher HCC risk compared with non-users (HR 1.88; 95% CI 1.07-3.29), which persisted after adjustment for key covariates (aHR 1.74; 95% CI 0.99-3.06). A dose-response trend was observed (p for trend 0.043). The authors conclude that these findings suggest a possible link between sustained tibolone use and HCC risk, warranting confirmation in larger populations, and longer follow-up (graphical abstract).