Contraceptive steroids: Modifications of carbohydrate and lipid metabolism

Abstract

Although chronic ingestion of contraceptive steroids may produce a variety of metabolic changes, their effect on carbohydrate and lipid metabolism appears to be related to the age and predisposition to metabolic disease of the recipient and to the amounts and relative proportions of estrogen, nortestosterone, and progesterone derivatives in the birth control preparations employed. In healthy intact young women, the separate administration of either synthetic estrogens or progesterone derivatives or nortestosterone derivatives does not consistently alter glucose or insulin metabolism as assessed by serum glucose or insulin concentrations after overnight fasting or following glucose administration. However, the concurrent administration of mestranol or ethinyl estradiol with a nortestosterone derivative produces deterioration of glucose tolerance, which is not observed during concurrent synthetic estrogenprogesterone derivative administration. The changes in glucose tolerance produced by birth control pills are superimposed on the deterioration of glucose tolerance observed with aging. Also, women with borderline pancreatic insulin reserve appear more likely to develop abnormal glucose tolerance than normal women when challenged with contraceptive steroids, although deterioration of glucose homeostasis does not seem to occur frequently in insulin-requiring diabetics using birth control pills. Concurrent mestranol-nortestosterone derivative administration generally enhances the peripheral circulating insulin response to a glucose challenge in normal women and in rhesus monkeys, whereas the individual contraceptive steroids and concurrent synthetic estrogen-progesterone derivative administration generally produce little measurable effect on circulating insulin concentrations. However, the rhesus monkey is not an ideal model for studying the metabolic effects of contraceptive steroids because its glucose tolerance improves with concurrent mestranol-norethindrone administration. No other suitable animal model has been developed for studying the effect of contraceptive steroids on carbohydrate metabolism. Estrogen administration leads to increased fasting serum triglyceride concentrations. Nortestosterone derivatives (but not 17 α-acetoxyprogesterone derivatives) counteract the hypertriglyceridemic effect of estrogens. Both of these effects appear to be dose-related. Contraceptive steroid-inducd hypertriglyceridemia primarily appears to be due to increased hepatic production of triglycerides, although plasma clearance of the triglycerides also seems to be reduced by the estrogen component of contraceptive steroids. Changes in serum cholesterol concentrations produced by birth control pills are small and are related to the age of the patient. In women over 40, total serum cholesterol concentrations decrease during birth control pill use; in women under 40, they increase. When increases in total serum cholesterol concentrations occur, they appear to be related to the amount of nortestosterone or progesterone derivative ingested. The possible relationship of these complex contraceptive steroid-induced changes in carbohydrate and lipid metabolism to the long-term development of cardiovascular diseases is discussed, although the mechanisms involved remain obscure.