Risk factors associated with the use of sex hormones

Abstract

World wide, millions of women have been exposed to potentially carcinogenic steroids in the form of oral contraceptives. Neoplastic liver disease has been associated with the use of such agents, but a direct causal relationship has not been proved. Oral contraceptives may protect against some diseases. Other female sex hormones used in therapeutics probably carry little hazard. Anabolic androgen use is also associated with neoplastic liver disease. Arguments are put forward for caution in the use of male and female sex hormones in man, particularly in regions where possible initiating agents (viruses, oncogenes) may be endemic.

PIP: The risk of contracting neoplastic liver disease after taking synthetic sex hormones, either estrogens or androgens, is discussed. Since the 1st reports that oral contraceptives were associated with liver neoplasms in the 1970s, tests on laboratory animals have suggested that sex steroids act as promoters of hepatocarcinogenesis in suitably initiated animals, and that some hormones act as weak complete carcinogens in certain lab hosts. It is known that oral contraceptives induce benign hepatic adenoma: hundreds of cases have been reported. These adenomas regress when women stop taking orals. The possible progression to malignant lesions is difficult to assess. Although a 1982 case review of women with hepatocellular carcinoma concluded that the association was a coincidence, 2 more recent epidemiological studies have proposed that there is a possible link between pills and hepatocarcinoma as well as cholangiosarcoma. In favor of the association is the finding that the histopathology of carcinoma in pill users differs from that in nonusers. Arguing against a causative role is the fact that natural cyclic estrogen levels are much higher than those found in pill users. Overall, the risk of developing liver cancer is far lower than the risk of other serious consequences of pill use, for example thromboembolism, and must be judged in the context of the many protective effects of the pill. The estrogen DES or diethylstilbestrol is no longer being used, but cases of clear-cell adenocarcinoma are still appearing in the daughters of its users. Anabolic androgens, prescribed therapeutically or abused, are known to cause liver neoplasms, primarily hepatocellular carcinoma, but also adenomas, focal nodular hyperplasia, cholangiosarcoma and angiosarcoma. The legitimate use of these steroids is on a much smaller scale, and for short periods of time, compared to oral contraceptives, so the causative role of androgens in neoplasia is less well known. With any of these drugs, especially in areas where potential cancer initiators such as oncogenes or viruses are endemic, careful screening is vital for safe use.