Effect of ethinyl estradiol and norethisterone acetate on adrenal and some other tissues of the rat

ABSTRACT

Alkaline phosphatase activity [AP] of the adrenal cortex of rats was determine under the effect of ethinyl estradiol [EE] and/or norethisterone acetate [NA], the two components of the contraceptive pill Gyn-Anovlar [Schering A.G. Berlin]. LA poathological study was also carried out to examine the effects of EE and NA on other tissues, mainly the liver, lungs, spleen and ovaries. EE in a dose of 10 micro/rat/day for 2 weeks caused a significant increase in the weight of the adrenal but no significant increase in the AP/gm cortical tissue. The 25 and 50 micro doses for the same period caused a significant increase in both adrenal weight and AP. When treatment was prolonged to 6 weeks no effect on adrenal weight or APO was detected. The same findings obtained with NA in a dose of 7 mg/rat/day for 2 weeks. The 14 mg dose of NA for the same period caused a significant increase in adrenal weight but no effect on AP. The 21 mg dose caused a significant increase in adrenal weight accompanied by significant decrease in AP/gm cortical tissue. Treatment with NA for 6 weeks caused a rise in adrenal weight and AP with the 7 mg dose, then a decline in AP with the 14 mg dose, and a decline in both adrenal weight and AP with the 21 mg dose. As regards the effects of EE and NA on other tissues, EE was found to have a powerful stimulatory effect on the reticulo-endo-thelial system [RES] as well as toxic effects on the liver. NA did not produce such lesions except with the large doses and prolonged periods of treatment. In addition NA produced cholestasis in the liver associated with staining of the liver cells with bile. Combination of EE and NA in the form of gyn-anovlar produced more powerful stimulation of RES and decreased the toxic manifestations of either component. As regards the ovaries, administration of 50 ug EE for 6 weeks produced profound hyperplasia of the granulose cells of the Graafian follicles and inhibited ovulation, however, NA did not inhibit ovulation. With gyn-anovlar, the effect of EE on the ovaries seemed to predominate and ovulation was inhibited