Studies of the components of an oral contraceptive agent in albino rats. I. Estrogenic component

Abstract

Albino rats were fed ethynylestradio to the diet for 2 yr at dosage levels (0.006--0.008 and 0.06--0.08 mg/kg) of about 10 and 100 times the recommended human dose as used in a combination oral contraceptive. The treated rats had typically estrogenic effects on a dose-related basis, including growth retardation, alopecia, liver enlargement and increase in cell alterations, and increased survival rate. Females had uterine changes and males had gonadal atrophy. At the higher dose level, females had gonadal atrophy and adrenal enlargement and animals of both sexes had cystic mastopathy. Rats of either sex given the higher dose had an increased incidence of liver neoplastic nodules and pituitary chromophobe adenomas, and males had an increased incidence of mammary fibroepithelial tumors. Treated rats of either sex had neither increased tumor incidence rates overall, nor increased numbers of tumors compared to control rats. In fact, females had a significant delay in onset of tumor development and less potential for their ultimate development than control females.