Species: Dog Strain/breeder: Beagle Sex: Female Age: 2 years Study type: Chronic toxicity study Treatment: i.g., 9 months, non-steroidal anti-hormone Animal status: Scheduled death, end of study Clinical findings: - Organ: Ovary Macroscopic finding(s): Ovaries enlarged (4 cm in diameter); cysts (up to 0.5 cm in diameter; weight increase of 300% Staining: H&E Literature:

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Abstract

Female sexually mature Beagle dogs were treated daily by gavage with an anti-estrogenic compound for a period of 9 months. During the treatment period no clinical signs of disturbance in hormonal homoeostasis were observed. The animals were sacrificed at study termination. At necropsy ovaries were markedly enlarged and showed multiple cysts with a diameter of approx. 5 mm. The ovarian weights were increased up to 300 % in comparison to the control animals. Histologic examination revealed a markedly increased number of follicles, many with luteinisation of the stratum granulosum and partly also of the theca cells. The formation of interstitial glands was markedly increased. There were no signs of ovulation and a complete lack of corpora lutea. Some follicles were cystic. These alterations are attributed to interference of the test article with the normal feedback regulation of estrogens. This interference results in increased secretion of GnRH, which in turn activates gonadotrophins to stimulate follicle growth. Due to a block of estrogen induced ovulation by the anti-estrogen on the pituitary level ovulation cannot take place. The lack of ovulation explains the missing formation of corpora lutea and the persistence of follicles.