The recent publication in Volume 55 of HEPATOLOGY Higher Serum Testosterone Is Associated with Increased Risk of Advanced Hepatitis C-Related Liver Disease in Males1 concluded that serum total testosterone levels are associated with higher rates of fibrosis and inflammation in hepatitis C virus (HCV)-infected men. The hypothesis was raised that serum testosterone may be implicated in the pathogenesis of HCV-related advanced liver disease in males.
While this publication investigated the association of total serum testosterone with fibrosis scores and inflammatory activity, sex estradiol levels were not determined.
The liver is a hormone-sensitive organ, and in fact both normal liver and hepatocellular carcinoma tissues from male and female mammals have been shown to express specific estrogen receptors (ERs). Experimentally, estrogens may act as liver tumor inducers or promoters in vivo.2, 3 In fact, estrogens are involved in the regulation of hepatocyte proliferation: a “feminization” of the hepatic microenvironment occurs after partial hepatectomy in rats and humans with an increase in estrogen levels and a concomitant reduction of testosterone levels.4, 5 The source of estrogens in men is from the aromatization of androgens and, broken down in the liver, the relationship may relate to the severity of liver disease. Therefore, serum total testosterone is not an accurate reflection of sex hormone status in cirrhosis and estradiol levels should also be determined in this patient group.