Oral Contraceptive Treatment Decreases Arterial Low Densit Lipoprotein Degradation in Female Cynomolgus Monkeys

The effect of oral contraceptive therapy on early events in atherogenesis was studied in female cynomolgus monkeys. After a 1-month dietary challenge, monkeys were randomized into three groups stratified by total plasma cholesterol and high density lipoprotein cholesterol concentrations. The monkeys were then fed a cholesterol-containing diet for 16 weeks. This relatively short period ensured that studies were done before any treatment-induced differences in arterial morphology occurred. Monkeys were treated with either diet alone (control group), with the addition of a monophasic oral contraceptive (equivalent to a human dose of 50 ,ug ethinyl estradiol and 500 jig norgestrel per day), or with a triphasic oral contraceptive (equivalent to a human dose of30-40 jug ethinyl estradiol and 50-125 ,ug levonorgestrel per day). Twenty-four hours before necropsy, low density lipoproteins (LDLs) labeled with 1311 and LDLs labeled with the residualizing label '25I-tyramine cellobiose were injected into the animals. The arterial LDL degradation rate, amount of undegraded LDLs, and total LDL accumulation were then determined. Although there were regional differences in LDL metabolism, both treatments decreased the rate of LDL degradation and LDL accumulation in the coronary arteries and other arterial sites. Treatment also resulted in significantly lower LDL molecular weights. Despite a trend toward a more atherogenic lipid profile (decreased high density lipoprotein cholesterol and increased total plasma/high density lipoprotein cholesterol ratio), oral contraceptive treatment may inhibit atherogenesis by decreasing arterial LDL degradation. (Circulation Research 1993;72:1300-1307) KEY WoRDs * atherosclerosis * cynomolgus metabolism * oral contraceptives * females