After 4 years of a long-term contraceptive steroid safety study, the incidence and the histologic types of mammary dysplasia produced are shown to be similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid-stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17 beta-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose-related manner in both treatment groups. Levels of triiodothyronine, cortisol, and 17 beta-estradiol (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary-gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of beagles with doses of progesterone or medroxyprogesterone 1 to 25 times the human contraceptive dose or luteal phase (dog) levels, respectively, results in a dose-related incidence of mammary nodules.
PIP: The results of a 4-year longterm study of contraceptive safety in mammals are discussed. The animals were treated with either MPA (medroxyprogesterone acetate) or progesterone. Serum insulin, thyroid-stimulating hormone, triiodothyronine, growth hormone, prolactin, 17 beta-estradiol, progesterone, and cortisol were measured by radioimmunoassay on samples collected after 45 months of treatment. No increased incidence of mammary tumors were noted in rats, mice, or monkeys. An increased incidence of mammary dysplasia was, however, noted in dogs. MPA and progesterone produced similar incidence rates, types, and numbers of nodules per animal. The incidence of mammary nodules was dose-related. Microscopic examination of the nodules indicated a similar histology and distribution of change in bitches treated with both substances. Serum prolactin, growth hormone, and insulin responses were similar in both groups. Clinical studies with women being treated with either MPA or progesterone have shown no evidence of treatment-related mammary dysplasia. These studies revealed several significant differences in hormonal response to exogenous progestational compounds between dogs and humans.