EFFECTS OF LOW-DOSE ORAL-CONTRACEPTIVES ON VERY LOW-DENSITY AND LOW-DENSITY-LIPOPROTEIN METABOLISM

Oral contraceptives (OC) raise plasma triglyceride and VLDL levels, wh ich may be of concern, since some conditions characterized by elevated triglycerides are associated with atherosclerosis. To identify the re sponsible mechanism, we studied 11 healthy premenopausal women, 5 of w hom were taking OC containing 0.035 mg ethinyl estradiol, and 6 of who m were not. Their rates of VLDL and LDL metabolism were measured by en dogenously labeling apoB, the protein component of VLDL and LDI, by an intravenous infusion of deuterated leucine. OC use had the greatest e ffect on the large, triglyceride-rich VLDL subfraction (Sf 60-400), in creasing plasma levels threefold and production rates fivefold (P < 0. 05). Among OC users, small VLDL (Sf 20-60) levels were 2.2 times highe r, and production rates were 3.4-fold higher (P < 0.05). The fractiona l catabolic rates of large and small VLDL were similar among OC users and nonusers. LDL levels and metabolic rates were not significantly di fferent between the two groups. Thus, contemporary low dose OC substan tially raise VLDL levels by increasing the production rate of large, t riglyceride-rich VLDL, and not by slowing VLDL catabolism. Since VLDL catabolism is not impaired, we speculate that the hypertriglyceridemia induced by OC may be less atherogenic than that of hypertriglyceridem ia resulting from impaired lipolysis. This may explain why long-term O C use does not appear to promote atherosclerosis.