Serum testosterone: Estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients

The reason for the large male predominance in the occurrence of hepatocellu lar carcinoma (HCC) remains unknown, and sex hormones may contribute to thi s phenomenon. We examined possible associations of serum levels of testoste rone, free testosterone, estradiol, sex hormone binding globulin, and testo sterone:estradiol ratio (T:E2 ratio) with HCC development in a follow-up st udy of 46 Japanese male patients with liver cirrhosis predominantly of hepa titis C virus origin (76%). Serum samples were collected between December 1 985 and December 1987, and the patients were completely followed until the end of 1995 for an average of: 5.1 years. During the follow-up period, 20 p atients (43%) developed HCC, Univariate analysis demonstrated that serum T: E2 ratio and testosterone were significant predictors of HCC; the hazard ra tios land 95% confidence intervals) in the middle and upper tertiles relati ve to the lower tertile were 2.0 (0.5-7.6) and 4.0 (1.1-14.6; P trend = 0.0 3) for T:E2 ratio and 0.8 (0.2-3.1) and 2.9 (1.0-8.5; P trend = 0.05) for t estosterone. Adjustment for age, serum albumin, hepatitis virus markers, an d other clinicobiological variables substantially increased the correspondi ng hazard ratios. In multivariate analysis, serum free testosterone appeare d to be associated with increased risk, yet independent associations with e stradiol and sex hormone binding globulin were not evident. These results i ndicate that elevated serum testosterone, together with decreased serum est rogens, may promote the development of HCC in cirrhosis.