Decreased Uterotropic Potency of Oral Contraceptives in Rats Pretreated with Phenobarbital¹

Abstract

Treatment of immature female rats with phenobarbital for 4 days inhibits the uterotropic action of synthetic estrogens such as ethynyl estradiol, ethynyl estradiol-3-methyl ether (mestranol) and diethylstilbestrol. Treatment of rats with as little as 0.25 mg of phenobarbital/kg twice daily for 4 days causes a 33% inhibition in the uterotropic action of a 1 μg oral dose of ethynyl estradiol-3-methyl ether. The inhibitory effect of phenobarbital administration on the action of diethylstilbestrol-3H is paralleled by decreased radioactivity in the uterus and by increased levels of NADPH-dependent enzymes in liver microsomes that metabolize diethyl-stilbestrol. Studies on the estrogenic activity of synthetic progestational steroids in rats revealed that the administration of norethindrone and norethynodrel increases the uterine wet weight and this effect is inhibited by pretreatment with phenobarbital. (Endocrinology 83: 149, 1968)