Comparative studies of the ethynyl estrogens used in oral contraceptives: effects with and without progestational agents on plasma cortisol and cortisol binding in humans, baboons, and beagles.
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abstract
Ethynylestradiol and mestranol, in doses ranging from 50 to 100 g/day, were given to women in 21-day cycles; baboons and beagle dogs received 1 and 4 g/kg/day in a similar regimen. After a number of such cycles, megestrol acetate, norethindrone acetate, or dl-norgestrel was given concomitantly. Plasma cortisol and percentage binding of cortisol were determined, and the level of free cortisol was calculated. Over this dosage range the effect of the two kinds of estrogen was indistinguishable. In women, 100 g/day produced slightly higher levels of total plasma cortisol than 50 g/day, but no other dose-related differences were seen in any of the three species. Estrogen caused a rise in total cortisol (implying an increased synthesis of transcortin by the liver) in humans and baboons; in the beagle, total cortisol fell transiently. In all three species, the percentage binding of cortisol increased during estrogen administration. There was a very slight, statistically demonstrable increase in total and free cortisol levels in humans and baboon, none in dogs. Of the three progestational compounds, norethindrone acetate and norgestrel produced a slight decrease in total cortisol, whereas megestrol had no effect in humans. The free cortisol was unaltered by these compounds. In both the baboon and the dog, the response was complex, and different from that seen in human subjects. The dog appears to be an inappropriate surrogate for man in the study of these hormonal effects. The validity of the baboon with respect to this progestin-induced effect requires further study; however, its response to estrogens is similar to that of man.
