title: Role of oral contraceptive agents in the pathogenesis of liver tumors.
abstract: Since the introduction of oral contraceptive steroids in 1960 there has been a sharp increase in the incidence of benign liver tumors. Epidemiologic and other evidence links focal nodular hyperplasia and hepatic cell adenoma to the use of these agents. The risk increases with long-term exposure. The majority of patients were less than 35 years old. Most patients were exposed to mestranol (ME) alone or alternately with ethinylestradiol, both synthetic steroidal estrogens. Inability to demethylate ME in the smooth endoplasmic reticulum of hepatocytes may allow massive accumulation of oncogenic metabolites. This is probably a pharmacogenetic variable in a small number of women. Cholestasis, hypervascularity, induction of intracellular enzyme systems, thrombogenesis, and thickening of arterial and venous walls are other known effects of synthetic estrogens and progestogens. All may contribute to the pathogenesis of liver tumors. Many patients are asymptomatic until there is rapid expansion of the tumor. Pain occurs when Glisson's capsule stretches. Intrahepatic bleeding and liver rupture are common sequelae. Ligation of the hepatic artery may be lifesaving in the face of exsanguinating liver bleeding. Reports of regression with observation alone are encouraging. Instances of progression of unresected adenomas to rupture during subsequent pregnancy dictate avoidance of sex steroids in patients with hepatic neoplasia. Sonography, computerized axial tomography, radionuclide scans, and selective celiohepatic angiography are useful methods for the diagnosis of liver tumor in the symptomatic patient. There is a primary need to develop biochemical methods for detecting patients at risk for developing liver tumors. Epidemiologic research and central reporting of case histories are needed in the search for common factors.
mesh_terms: D000328:Adult; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000175:diagnosis / Q000601:surgery; D003276:Contraceptives, Oral / Q000009:adverse effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000378:metabolism; D005260:Female; D006222:Hamartoma / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D006965:Hyperplasia; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000601:surgery; D008297:Male; D008656:Mestranol / Q000009:adverse effects / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D051381:Rats; D012422:Rupture, Spontaneous
chemical_list: D003276:Contraceptives, Oral; D004997:Ethinyl Estradiol; D008656:Mestranol