Tibolone Use Associated With Elevated Hepatocellular Carcinoma Risk: Findings From a Nationwide Cohort

Tibolone, a synthetic steroid with estrogenic, progestogenic, and androgenic activity, is widely prescribed for menopausal symptoms, but its association with hepatocellular carcinoma (HCC) remains unclear. Using data from 117,271 women aged ≥ 45 years in the Korean National Health Insurance Service-Health Screening Cohort, we 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 (hazard ratio [HR], 1.88; 95% CI, 1.07-3.29), which persisted after adjustment for key covariates (adjusted hazard ratio [aHR], 1.74; 95% CI, 0.99-3.06). A dose-response trend was observed (P for trend = 0.043). These findings suggest a possible link between sustained tibolone use and HCC risk, warranting confirmation in larger populations and longer follow-up, ideally through well-designed prospective studies.