Histopathological Study of Female Beagle Dogs for Four Year Treatment with Subcutaneous Implantation of Chlormadinone Acetate (CMA)

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The histopathological changes related to chlormadinone acetate (CMA) implantation were examined using female beagle dogs given 10mg/kg for four years. All control animals showed sign of estrus during the experiment, with periods of anestrus of normal duration. In contrast, estrus was completely inhibited in the CMA-implanted animals. Histopathologically, 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 the liver, adrenal, mammary gland, gallbladder and implanted site. Furthermore, the intensity of staining and number and size of ACTH-and LH-positive cells in the pituitary sections of CMA-implanted animals were not different from control animals. It was concluded, therefore, that subcutaneous implantation of CMA is a potential drug-delivery system for reducing changes due to antigonadotropic and glucocorticoid-like activities and characteristic histopathological changes in the uterus due to progestagenic activity.

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