Effects of Oral Contraceptives on Glucose Metabolism

Abstract

Techniques to measure the effect of combined oral contraceptives (OCs) on glucose metabolism include the oral glucose tolerance test (OGTT) intravenous glucose tolerance test (IVGTT) and the euglycemic or hyperglycemic hyperinsulinemic clamp techniques. There is concern about OCs having possible diabetogenic effects. Studies using the OGTT tend to demonstrate that OCs alter carbohydrate metabolism with increased glucose intolerance. The OCs that appear to have the greatest degree of glucose intolerance are those with estrogen doses greater than 50 mcg and those with levonorgestrel. During the OGTT levonorgestrel seems to effect the greatest degree of hyperinsulinema. In studies using the IVGTT levonorgestrel-associated OCs induced the greatest degree of insulin resistance (e.g. 2nd phase insulin increased by 60-90%) but did not change insulin half-life. Their glucose levels decrease more slowly after IVGTT increasing the stimulus of endogenous insulin secretion later in the test. The hyperglycemic hyperinsulinemic clamp examines pancreatic insulin secretion and glucose uptake under hyperglycemic hyperinsulinemic conditions. Euglycemic clamp studies show that OCs may be associated with a decrease in insulin sensitivity under euglycemic hyperinsulinemic conditions suggesting a possible postreceptor defect involving the insulin receptor. Women with insulin-dependent diabetes women with noninsulin-dependent diabetes and women with a past history of gestational diabetes may not be able to rise to an adequate hyperinsulinemic response to the increased glucose challenge during OC use and may have increases in the circulating plasma glucose and insulin levels.