Age modulates estradiol's dual role in hepatocellular carcinoma recurrence after ablation: A prospective...

The association between estrogen and hepatocellular carcinoma (HCC) remains controversial. This study explored estradiol (E2)'s effect on HCC recurrence post-minimally invasive treatment and age's critical modifying role. 247 male HCC patients were prospectively enrolled, underwent radiofrequency ablation, and followed up for 36 months. Confounding factors were analyzed via cubic spline regression Cox model, with hierarchical analysis for age-specific effects. E2 and age showed a nonlinear correlation with HCC recurrence, with age identified as a confounding factor for E2. The cutoff values were 53/67 years (age) and 42 pg/ml (E2). For patients <53 years, E2 ≥42 pg/mL was linked to a significantly lower cumulative recurrence rate (CRR, p = 0.002); for 53-67 years (p = 0.065), no significant difference was observed; for >67 years, E2 ≥42 pg/mL was associated with a significantly higher CRR (p < 0.001). Thus, age modulates E2's dual role: protective (<53 years), transitional (53-67 years), and risk-promoting (>67 years).