Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormone-binding globulin.

We measured serum sex hormone-binding globulin (SHBG) using a radioimmunoassay developed by us, testosterone (T), estradiol (E2), free T and free E2 in 50 male patients with non-alcoholic liver cirrhosis (compensated: 30, decompensated; 20) and age-matched healthy male subjects, SHBG was significantly increased in patients with liver cirrhosis compared with healthy subjects. The high serum SHBG level in male compensated cirrhotic patients tended to decrease with progression to the decompensated state. Serum cholinesterase showed a positive correlation with SHBG in liver cirrhosis. Serum free T and the T/SHBG ratio decreased, while serum E2, free E2, and the E2/T and the free E2/free T ratios increased in liver cirrhosis, resulting in estrogen predominance and feminization of male patients. These changes were more marked in decompensated than compensated liver cirrhosis. An increased free E2/free T ratio was observed in patients with gynecomastia, palmar erythema or vascular spider. The T/SHBG ratio showed a positive correlation with serum free T, suggesting that it can be used as a free T index in liver cirrhosis. From these observations, it is suggested that serum SHBG plays an important role, by regulating the serum free T level in the occurrence of feminization in male patients with non-alcoholic liver cirrhosis.