Dose-Dependent Effects of Ethinyloestradiol, Diethylstilboestrol and Oestradiol on the Metabolism of 4-Androstene-3, 17-Dione in Rat Liver Microsomes

Abstract

The effects of administration of ethinyloestradiol (EtE2), 0.1, 0.5 or 1 \ g=m\ g per day, diethylstilboestrol, 5, 100 or 500 \ g = m\ g per day, and oestradiol, 1 or 100\g=m\gper day for 12 days on the hepatic microsomal metabolism of 4-[4-14C]androstene-3,17-dione were studied in castrated male and female rats.When rats were given EtE2 in daily doses of 0.1 and 0.5 \g=m\g the activities of the 3\g=a\-and 17\g=b\-hydroxysteroid oxidoreductases increased in both male and female rats. A similar tendency was noted for the 5\g=a\-reductasein female rats. On the other hand, the activities of the 3\g=b\-hydroxysteroid oxidoreductase and 7\g=a\-hydroxylaseenzyme systems were suppressed in both male and female rats already after administration of 0.1 \ g=m\ g of EtE2. Diethylstilboestrol, administered in doses of 100 and 500 \ g=m\ g, and oestradiol, given in a dose of 100 \g=m\g,suppressed the microsomal enzyme activities whereas the lower doses of 5 \g=m\g of diethylstilboestrol and 1 \ g=m\ g of oestradiol were without effects.The results indicate that oestrogenic compounds given in doses higher than the physiological one have a suppressing effect on microsomal steroid metabolizing enzyme activities. Ethinyloestradiol has a stimulating effect on certain microsomal enzyme activities and an inhibiting effect on others when administered in an amount of 0.5 \g=m\g\ m=. \ kg\m=-\1per day. The findings are discussed in relation to recent reports on impaired drug metabolism in women taking contraceptives.

Ethanol Metabolism in Women Taking Oral Contraceptives

“…It recently has been suggested that synthetic estrogens as contained in oral contraceptives may impair liver microsomal drug and steroid metabolism. 16 Animal studies also support this possibility. It has been reported that rats with high levels of synthetic estrogens (given oral contraceptives) voluntarily consumed less alcohol."…”