Liver tumors and oral contraceptives: pathology and pathogenesis

Since 1973, over 200 cases of liver masses associated with oral contraceptive usage have been reported. Nearly 100 have been liver cell adenomas and 11 have been hepatocellular carcinomas. Focal nodular hyperplasia (FNH) appears only coincidentally associated, but with a particular hemorrhagic tendency. Bile duct proliferation distinguishes FNH from liver cell adenoma. Two typical cases are presented. Right upper quadrant pain with intra-abdominal hemorrhage is the single most common clinical presentation. Mestranol-containing preparations appear more hazardous. Liver enzymes are usually normal or slightly elevated. Most cases are resectable. Lesions have regressed following discontinuation of pill use; however, close observation is required. Although mammalian liver possesses estrogen receptors, these agents have induced few or no liver tumors in numerous animal studies. Mutagenicity tests indicate that estrogenic compounds do not damage DNA. However, diethylstilbestrol can promote the growth of rat hepatomas initiated by a carcinogen. Further experimental studies may better characterize estrogens as hepatoma promoters.