J. Parks, Susan J. Pelkey, J. Babiak
Mar 1, 1989
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Arteriosclerosis, Thrombosis, and Vascular Biology
Abstract
Seventy-three adult female cynomolgus monkeys fed an atherogenic diet were studied to determine the effect of two different combination contraceptive steroid preparations containing equivalent amounts of estrogen but different progestln components on plasma NpkJs and lipoproteins. Our hypothesis was that any high density llpoproteln (HDL) lowering effect of the contraceptive steroid preparations was proportional to the rise In total serum cholesterol caused by the progestins. For 2 years, one group (Ovral [Wyeth Laboratories], n=23) received 75 HQ norgestrel and 7.5 ng ethinyl estradiol dally, while another (Demulen [Searle & Co.], n=25) received 150 /tg ethynodlol dlacetato and 7.5 /ig ethinyl estradiol dally. The control group (n=24) received no treatment On average, the two oral contraceptive groups had higher total serum cholesterol and triglycerlde concentrations but lower HDL cholesterol concentrations and smaller low density lipoproteins (LDL) compared with the control group. There was an Inverse relationship between total serum cholesterol and HDL cholesterol for all three groups, but at any given total serum cholesterol concentration between 350 and 500 mg/dl, the Ovral group had HDL cholesterol concentrations that averaged 37% and 14% lower than the control and Demulen groups, respectively. The decrease In HDL concentrations with oral contraceptive treatment was associated with a sharp decrease In (HDL2b)gge protein (82% for Ovral and 59% for Demulen) and a corresponding Increase In (HDL3b,c)gge. protein as determined by gradient gel electrophoresls. Of 23 animals In the Ovral group, six had HDL subtractions >10 nm diameter (HDL2b)gge. compared with 22 of 24 animals in the control group. Although LDL size, on average, was smaller and plasma triglycerides were greater with oral contraceptive treatment compared with controls, there was no apparent relationship between LDL size and plasma trlglyceride concentrations. We conclude that: 1) the smaller LDL particles of Demulen vs. control female cynomolgus monkeys was not related to the differences In plasma triglycerlde concentrations between the two groups, and 2) treatment of female cynomolgus monkeys fed cholesterol with Ovral results in additional HDL» lowering compared with that of dietary cholesterol alone or dietary cholesterol with Demulen.