Preponderance of serum and intra-hepatic 5 alpha-dihydrotestosterone in males with hepatocellular carcinoma despite low circulating androgen levels

To investigate possible influences of the sex-steroid milieu on hepatocellular carcinoma (HCC) and vice versa, circulating and intra-hepatic sex-steroid levels were investigated and compared with the levels in cirrhosis alone. In cirrhotic men with HCC, serum 17 beta-oestradiol levels were normal, unlike the elevated levels in men with cirrhosis alone. Total and free levels of testosterone and 5 alpha-dihydrotestosterone (DHT) were lower in patients with HCC than in cirrhotic or normal men; the greater decrease in testosterone levels caused an elevated DHT: testosterone ratio. Hypothalamic-pituitary axis dysfunction demonstrated for HCC and cirrhotic groups could not explain the differences in sex-steroids between them. Compared with normal tissue, HCC cytosol had lower testosterone and similar DHT levels; both androgens were higher than in cirrhotic tissue, and the intracellular DHT: testosterone ratio in the tumour was much higher than in control tissue. Results suggest alterations in sex-steroid metabolism in HCC favouring hepatic accumulation of 5 alpha-reduced metabolites aided by the elevated intracellular sex-hormone binding globulin levels shown in HCC tissue.