A total of 213 treated and 16 control monkeys comprising 12 experimental groups was evaluated for determination of the long-term (10 years) effects of various dosages of a variety of synthetic
oral contraceptive steroids on the mammary glands of rhesus monkeys. The
steroid hormones included
mestranol,
ethynerone, a combination of
mestranol and
ethynerone, chlorethynyl
norgestrel plus
mestranol, and
anagestone acetate plus
mestranol. Various degrees of physiologic lobular
hyperplasia and lactational changes were observed in association with all of these
steroid hormones; these changes appeared dose-dependent.
Mestranol caused a proliferative atypia ranging from a minimal to a moderate degree in 8 of 34 (23%) animals, but it was not dose-related. Eleven of 15 monkeys (73%) administered
ethynerone developed proliferative atypia, ranging in degree from minimal to severe, including one invasive
carcinoma and 2 lesions resembling
intraductal carcinoma in the human. The
mestranol and
ethynerone combination produced a proliferative atypia in 22 of 52 animals (42%), including five identical to
intraductal carcinoma in the human and one identical to lobular
neoplasia. Of the 40 monkeys administered
anagestone acetate and
mestranol, 20 (50%) developed proliferative atypias; the atypias ranged from mild to severe and included five resembling
intraductal carcinoma in human breast. The
chloroethynyl norgestrel and
mestranol combination induced proliferative atypia in 25 of 52 monkeys (49%); six of these atypias were severe and indistinguishable from
intraductal carcinoma of the human breast; and one, if in the human breast, would reflect a solid variant of an invasive
carcinoma. Only 2 of the 16 control monkeys (12%) developed proliferative atypias, and these were of minimal to mild degree. The occurrence of severe degrees of atypia identical to
intraductal carcinoma in the human breast and invasive
carcinoma associated with
hormone administration suggests a carcinogenic effect.