Metabolic interrelationships, cardiovascular disease, and sex steroids

Future studies of the pharmacodynamics of oral contraceptives should encompass interactions between various areas of physiology rather than concentrate on single metabolic processes. Changes in one area of metabolism may affect other areas. Insulin plays a central role in metabolic control and, in addition to profound effects on carbohydrate and lipid metabolism, also affects the hematological system. Insulin has been proposed as a major physiological regulator of plasminogen activator inhibitor, and hyperinsulinemia is associated with increased blood coagulability and decreased fibrinoloysis. There is a close relationship between insulin and triglyceride metabolism, and this may affect factor VII activity in blood. There are many interactions between lipid metabolism and hematological factors. The apoprotein of lipoprotein (a) is structurally similar to plasminogen. Tissue factor pathway inhibitor, a regulator of coagulation, circulates in blood bound to LDL and HDL. Some fatty acids may act as a contact surface for activation of hematological factors. Dietary factors also need to be considered. Changes not only in the quantity but also in the composition of dietary fat influence lipid metabolism and also blood levels of a number of hematological factors. Other aspects of pharmacodynamic studies that require consideration and other factors that affect metabolic inter relationships are discussed. (C) 1998 Elsevier Science Inc. All rights reserved.