Comparative studies of the ethynyl estrogens used in oral contraceptives. VII. Effects with and without progestational agents on ultracentrifugally fractionated plasma lipoproteins in humans, baboons, and beagles

Abstract

Ethynyestradiol and mestranol, in doses ranging from 50 to 100 microgram/day, were given to women in 21-day cycles; baboons and beagle dogs received 1 and 4 microgram/kg/day in a similar regimen. After a number of such cycles, megestrol acetate, norethindrone acetate, or dl-norgestrel was given concomitantly. Protein, cholesterol, triglyceride, and phospholipid levels were determined in total plasma and in ultracentrifugally separated lipoprotein fractions. Over the dosage range studied, the effects of the two kinds of estrogen were indistinguishable. Except for human total plasma triglyceride, no dose-related differences were observed. The lowering of serum protein and the increase in cholesterol induced by estrogen were more pronounced in baboons and beagles than in human subjects. The cholesterol-depressing effect of progestational compounds observed in humans was very pronounced in baboons but absent in beagles. In all three species, estrogen increased the lipoprotein fraction cholesterol, except for human low-density lipoprotein cholesterol, which was decreased. Human plasma triglyceride and phospholipid increased on estrogen administration and were decreased by the progestins; in the two animal species, triglyceride is normally very low and the estrogen-induced changes were negligible; the phospholipid rose with estrogen but was unaffected by progestins. In sum, the two animal species show many similarities to, as well as important differences from, the human response of plasma lipids to various contraceptive steroids.

PIP: In this comparative study, ethinyl estradiol and mestranol (dose range, 50-100 microg/day) were given to women in a 21-day cycle; baboons and beagle dogs received 1 and 4 microg/kilog/day in a similar regimen. After a number of cycles, mestranol acetate, norethindrone acetate, or d,1-norgestrel was given concomitantly. Protein, cholesterol, triglyceride and phospholipid levels were determined in total plasma and in ultracentrifugally separated lipoprotein fractions. Effects of the 2 kinds of estrogens were indistinguishable over the dosage range studied. Except for human total plasma triglyceride (P .001), no dose-related differences were observed. Lowering of serum protein and increase in cholesterol induced by estrogen were more pronounced in the 2 animal species than in humans. The cholesterol-depressing effect of progestational compounds observed in humans was very pronounced in baboons but was absent in beagles. In all 3 species, estrogen increased the lipoprotein fraction cholesterol, except for human low-density lipoprotein cholesterol, which was decreased. Human plasma triglyceride and phospholipid increased on estrogen administration and were decreased by progestins. In beagles and baboons, triglyceride is normally very low and the estrogen-induced changes were negligible; phospholipid rose with estrogen but was unaffected by progestins.