Sex hormones and neoplasia: liver tumors in rodents

Abstract

The association of liver tumors in women and men with the use of oral contraceptives and anabolics, respectively, has drawn attention to the hepatotumorigenic effects of sex hormones. The available evidence from long-term carcinogenicity studies in various strains of mice, rats and hamsters indicates that sex hormones are hepatotumorigenic agents, although the incidence of liver tumors is, in general, low even at doses exceeding human exposure by a factor of one hundred or more. Among the three rodent species, mice appear to be the least sensitive. Under certain modulating conditions, however, a 100% incidence of hepatocellular carcinomas can be obtained with some estrogens in male Syrian golden hamsters. The mechanism of the hepatotumorigenic effect of sex hormones is far from being clear. Whereas their tumor promoting activity is generally recognized, there is recent evidence suggesting that some sex hormones may also have initiating potential. Although the incomplete understanding of the mechanisms responsible for sex hormone induced liver neoplasia seriously hampers the assessment of the human risk, it appears to be clear that sex hormones are important modulating factors determining the incidence of hepatic tumors in rodents and possibly in humans.