Preponderance of Serum and Intra-Hepatic 5α-Dihydrotestosterone in Males with Hepatocellular Carcinoma Despite Low Circulating Androgen Levels

The study investigated the levels of sex-steroids in men with hepatocellular carcinoma (HCC) compared to those with cirrhosis alone and healthy controls. It found that men with HCC had normal serum 17 beta-oestradiol levels, unlike the elevated levels in men with cirrhosis alone. Both total and free testosterone and 5 alpha-dihydrotestosterone (DHT) levels were lower in HCC patients than in those with cirrhosis or normal men, with a greater decrease in testosterone leading to an elevated DHT: testosterone ratio. This difference in sex-steroid levels could not be explained by hypothalamic-pituitary axis dysfunction, which was present in both HCC and cirrhotic groups. In HCC tissue, testosterone levels were lower and DHT levels were similar compared to normal tissue, but both were higher than in cirrhotic tissue. The intracellular DHT: testosterone ratio was much higher in the tumor than in control tissue, suggesting a shift in sex-steroid metabolism in HCC that favors the accumulation of 5 alpha-reduced metabolites, possibly due to elevated levels of sex-hormone binding globulin in HCC tissue.