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 diethylsilbestrol. Treatment of rats with as little as 0.25 mg of pheno-barbital/kg twice daily for 4 days causes a 33% inhibition in the utero-tropic action of 1 [mu]g 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 diethylstilbestrol. Studies on the estro-genic 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.