In view of continuous clinical reports of liver damage following oral contraceptive use, morphologic changes of the liver following the administration of a combined type of oral contraceptive (Norinyle) were studied in guinea pigs by light and electron microscopic examinations. Two interesting changes, one in Kupffer cells and another in the hepatocytes were observed. The Kupffer cells were hyperplastic and enlarged due to the phagocytosis of a large amount of fibrin which were apparently formed intravascularly and were being cleared by Kupffer cells. It is thought that enlarged Kupffer cells and excessive fibrin formation beyond the clearing capacity of Kupffer cells may lead to blockage of sinusoids resulting in a Budd-Chiari like syndrome. The nucleus of the hepatocytes showed mild enlargement and a clear nucleolar segregation which is regarded as one of the ultrastructural evidences of chemical carcinogenesis. Therefore, it is speculated that this change may be related to tumorigenesis in the liver following oral contraceptive administration. Other changes consisted of ischemic necrosis and fatty changes in occasional animals, alteration of mitochondrial configuration and hyperplasia of smooth endoplasmic reticulum in hepatocytes.
Animal ; Blood Coagulation/drug effects ; Contraceptives, Oral/adverse effects* ; Contraceptives, Oral, Combined/adverse effects* ; Guinea Pigs ; Liver/drug effects ; Liver/pathology* ; Liver/ultrastructure ; Mestranol/adverse effects* ; Norethindrone/adverse effects*