| Abstrakt: |
In a study that has been in progress for 8 yr, ethynerone (MK 665) plus mestranol, chloroethynyi norgestrel (Wy-4355) plus mestranol, anagestone acetate plus mestranol, ethynerone, and mestranol have been administered at levels up to 25 times the human use level to female beagle dogs and 50 times the human use level to female rhesus monkeys. Both species have shown a mild, nonprogressive, dose-dependent decrease in hemoglobin and hematocrits when treated with the three progestogen-mestranol combinations, mestranol, or ethynerone. Pyometra occurred in some dogs from progestogen-treated groups. Dogs from the groups that received the three progestogen-mestranol combinations and ethynerone alone developed more hyperplastic and neoplastic mammary nodules than control dogs. Dogs that received mestranol alone had no more mammary nodules than control dogs. None of the drugs has produced an increased incidence of mammary nodules in monkeys. Clinically malignant mammary tumors occurred in a small number of dogs that received each progestogen-mestranol combination but did not occur in control dogs or dogs that received only mestranol or ethynerone. Ductal epithelial hyperplasia was seen in mammary gland biopsies from some monkeys receiving each drug but was not seen in biopsies from controls. Diabetes mellitus developed in ten dogs from chloroethynyi norgestrei-mestranol and anagestone acetate-mestranol groups and in three monkeys from ethynerone-mestranol and anagestone acetate-mestranol groups. Generalized cystic hyperplasia of the gallbladder mucosa occurred in a small number of dogs from the anagestone acetate-mestranol groups. |
