Long-term administration of progesterone to the female beagle dog

Progesterone was administered sc to groups of 5 mature female beagle dogs for 74 weeks at doses of 0.083, 0.25 or 0.75 mg/kg/day for the first 12 weeks, 0.83, 2.5 or 7.5 mg/kg/day for the next 24 weeks, and finally 2.5, 7.5 or 22.5 mg/kg/day from weeks 37 to 74. Estrus was not observed in the animals apart from two while receiving 0.083 mg/kg/day. Reactions at injection sites caused minor hematologic and other changes characteristic of chronic inflammation. Similar changes occurred in control animals given the vehicle alone but the effects on the erythrocytes were enhanced by progesterone treatment. The hormonetreated animals became obese, and plasma cholesterol and blood glucose concentrations were marginally increased. The uterus showed marked changes, cystic endometrial hyperplasia being followed by sloughing of the endometrium with dystrophic calcification. Ovarian follicle muturation was arrested and the pituitary showed a predominance of acidophils. There was marked lobular hyperplasia of the mammary glands, and fibroadenomatous nodules were found in mammary tissue from two high-dose and one middle-dose animal.