Oral contraceptives: effects on carbohydrate metabolism, insulin like activity and histology of the pancreas

Abstract

The effect of the combination type oral contraceptive and its estrogen (mestranol) and progesterone (ethynodiol diacetate) components on the intravenous glucose tolerance test (IVGTT), intravenous tolbutamide test (IVTT), serum insulin like activity (ILA) and morphology of beta cells of the pancreas was investigated in female rabbits. The combination produced impairment of glucose tolerance in all animals after 24 weeks treatment. Fifty percent of animals in the estrogen treated group and 33.3 percent of animals in the progesterone treated group developed impairment of glucose tolerance after 24 weeks. A reduction in the glucose response to IVTT was observed in all the animals following 24 weeks treatment with the combination, estrogen or progesterone. A significant decline in fasting serum ILA and post glucose ILA was observed in animals treated with the combination and estrogen. A small but consistent decline in the serum ILA was observed in animals treated with ethynodiol diacetate. A rise in serum FFA paralleled the abnormality of glucose tolerance. Morphological changes in the cytostructure of pancreatic islets in the form of degranulation and degeneration of cells were observed in the pancreas of animals treated with the combination, and to lesser extent in animals treated with estrogen and progesterone. These observations indicate that the disturbances in carbohydrate and lipid metabolism produced by oral contraceptives may be associated with damage to beta cells and low circulating insulin in rabbits.