The effects of a mixture of mestranol and ethynerone on the female monkey

Abstract

Female monkeys given cyclic treatments (3 weeks on, 1 week off) of IN20 (one part of mestranol plus two parts of 20-chloro-17-hydroxy-19-nor-17α-pregna-4,9-dien-20-yn-3-one, or ethynerone) during 26 months, in daily doses of 0.05, 0.25, and 1.0 mg/kg displayed the following effects: 1. Initial, temporary, reductions of consumption of food and water and of growth rate. 2. Enlargement of the breasts and clitoris and reddish coloration of the face, nipples and perineum, the first two coloration effects apparently being due simply to vasodilatation. 3. An apparently dose-related increase in the concentration of total serum cholesterol. 4. Mild hypochromic anemia in a few individuals; this change was corrected by the administration of capsules containing both intrinsic and extrinsic hematopoietic factors. 5. Increased ability to bind 3H in estradiol by the vagina and the breast, but decreased ability to bind this label by the uterus. 6. Increased acidophilia within the pituitary gland. 7. Mild hyperplasia of the adrenal cortex. 8. Slight to moderate hyperplasia of the smooth endoplasmic reticulum of the liver, accompanied by cholestasis. 9. Lobuloalveolar and ductal hyperplasia within mammary tissue, with the appearance of small, apparently unbounded nests of disorganized epithelial cells, which seemed not to be invasive beyond the lobules. The ducts of the mammary glands contained a material that appeared to be a mixture of apocrine and lactational secretions. Mitochondria were less numerous, and lysosomes more numerous, than in normal breast tissue. Mitotic figures became progressively more common as the dose of IN20 was increased. 10. Atretic follicles and follicular cysts within the ovaries. 11. An inactive, edematous stroma with comparatively few simple, tubular glands within the endometrium of the uterus. Major conclusions were: 1. IN20 is capable of preventing ovulation and the production of secretory endometrium in the female rhesus monkey. 2. Changes having some, but not all, of the characteristics of malignancy were observed in the breasts of the monkeys in the 26-month study. Although the eventual development of malignancy with more prolonged exposure to IN20 cannot be ruled out, it should be noted that similar changes during the 17-month exposure were observed to be reversible after administration of the mixture was discontinued.