Absrruct.Long-term studies of megestrol acetate and chlormadinone acetate in 100 female dogs are in progress. Doses of zero, one, 10 and 25 times the expected human dose of megestrol acetate and 25 times the expected human dose of chlormadinone acetate (on a milligram per kilogram body weight basis) are being given daily. During the first 4 years, eight dogs from each of the five groups were killed. The principal gross findings included enlarged uteri with mucoid material in the lumina, mammary development in dogs given middle and high doses of megestrol acetate and chlormadinone acetate, and thickened gallbladder walls in dogs given high doses of each. Histologic evaluation showed inhibition of ovulation for progestogen-treated dogs and suppression of ovarian follicular development with the high doses. Cystic endometrial hyperplasia was slight in the low-dose dogs and moderate to severe in most of the high-dose dogs; a few also had ulcerative endometritis and pyometra. The mammary glands of dogs given the middle and high doses produced lobules, acini, and secretion exceeding natural metestrus. Slight to marked cystic mucinous hyperplasia occurred in the gallbladders of most dogs given the high doses. Two high-dose megestrol dogs had clinical signs and microscopic pancreatic, renal, and ocular changes indicative of diabetes mellitus.Uterine cystic glandular hyperplasia and pyometra have been known to be related to endocrine imbalances in female dogs for many years [5,6,23]. Similar changes have been produced in the female dog by using naturally occurring hormone progesterone [3,7,8, 201. The causal relationship of cystic glandular hyperplasia to the synthetic progestogen, medroxyprogesterone acetate, is well documented [l, 21. Clinical descriptions of mammary development and secretion are occasionally included in these reports [3,4], but most are for the uterus with no reference to the histologic changes in the other genital organs.

No abstract

No abstract

No abstract

No abstract