Influence of components of oral contraceptive on lipid metabolism

Oral contraceptives (OC) have been shown to enhance the risk of atherosclerosis. In the present study we sought to determine which component of the OC (containing 0.067 mg estrogen and 0.667 mg of progestin) counts for alteration in lipids profile. Female rats were administered with 0.067 mg of 17 beta-estradiol and 0.667 mg of norethindron acetate/kg body weight. Estrogen treatment exhibited higher levels of lipids in the serum and tissues. LDL-cholesterol increased by three folds but HDL-cholesterol decreased significantly, while progestin group showed decreased levels of lipids and LDL cholesterol. Elevated hepatic cholesterogenesis was observed as indicated by increased activity of HMG-CoA reductase and elevated incorporation of labelled acetate into liver cholesterol in estrogen group. On the other hand, progestin treatment did not alter the activity of HMG-CoA reductase and the rate of incorporation of labelled acetate into hepatic cholesterol. Hepatic degradation of cholesterol to bile acids however, decreased with estrogen treatment. No considerable changes were observed in hepatic bile acid levels in progestin group. Release of lipoprotein into circulation increased but their clearance from the circulation decreased as revealed by the activity of lipoprotein lipase (LPL) of extrahepatic tissues in estrogen group. With progestin treatment, activity of LPL increased significantly in adipose tissue. Activity of hepatic malic enzyme and glucose 6-phosphate dehydrogenase enhanced considerably in estrogen group, while activities of these enzymes were depressed with progestin administration. Thus results indicate that estrogen component of oral pills counts for major changes in lipid and lipoprotein metabolism favouring the development of atherosclerosis.