Three combinations of steroid contraceptive drugs (mestranol plus lynestrenol. norethindrone or norethynodrel) were given orally at effective antifertility doses for 30 days to rats, mice and guinea pigs. Eighteen hr after the last treatment, the animals were sacrificed for preparation of liver microsomal enzymes and the evaluation of mestranol metabolism in vitro. The results obtained indicate that these three animal species convert mestranol into ethynylestradiol. a hormonally active agent, which is further metabolized into more polar metabolites. A prior administration of contraceptive agents increases in rats and mice the disappearance of mestranol and the metabolism of ethynylestradiol in vitro. In guinea pigs the effect was much less marked. The results are discussed considering that the estrogen activity of mestranol in vivo depends on the availability of ethynylestradiol for the estrogen receptors.
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