Histopathological and Immunohistochemical Studies in Female Beagle Dogs during Four Years Treatment with Implantation of Chlormadinone Acetate(CMA)

The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10 mg/kg for four years. Estrus was completely inhibited in the CMA-implanted animals. In contrast, all control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. Histopathlogically, uterine sections from the CMA-implanted animals showed cystic glandular hyperplasia, but no histologic evidence of endometritis, myometritis, and pyometra was found. In the ovaries of the CMA-implanted animals, developing ovarian follicles were observed but no mature follicles were noted in addition to an absence of corpus luteum. No remarkable changes were observed in liver, adrenal, mammary gland, gallbladder, and implanted site. Furthermore, the intensity of staining and number of adrenocorticotropic hormone (ACTH)- and luteininzing hormone (LH)-positive cells in the pituitary sections of CMA-implanted animals were not different from the control animals. It was concluded, therefore, that subcutaneous implantation of CMA (10 mg/kg) is nearly equivalent to the minimal ovulation-suppressing dose.