Effects of the Anti-Progestin Aglepristone on the Uterine Tissue of Cats Administered Medroxyprogesterone Acetate

The effect of aglepristone, a progesterone receptor antagonist, on feline endometrial proliferation induced by medroxyprogesterone acetate (MPA), a contraceptive progestin, was investigated. Three groups each of six cats were studied: Group A, during inter-oestrus; Group B, given 50 mg MPA; Group C, receiving 50 mg MPA followed by 10 mg/kg aglepristone twice at 24-h interval 3 weeks later. Ovariohysterectomy was performed, and uterine tissue was collected from the mid part of the horn when the cats were confirmed as being in inter-oestrus (Group A), 3 weeks after the MPA administration (Group B), or 2 weeks after aglepristone administration (Group C). Uterine weights, relative uterine weights and uterine diameters were determined. The endometrial and myometrial thicknesses and the endometrial/myometrial ratios were determined in histological sections. Histological sections were also immunostained for proliferative activity [anti-proliferative cell nuclear antigen (PCNA) antibody], and progesterone receptor (anti-hPR) and percentage of positive cells in luminal vs glandular epithelium were determined for both parameters. PCNA and all morphological parameters except endometrial thickness were increased (p < 0.05) by MPA, and progesterone receptor was decreased compared to untreated cats. Aglepristone treatment had no significant effect compared to MPA alone. However, glandular proliferative activity was usually but not significantly lower in Group C than in Group B, suggesting a potential effect of the anti-progestin that might be clinically beneficial. Alternatively, this possible effect in the aglepristone group may reflect the longer time after MPA that these animals were examined. Whether lack of significant effect of the anti-progestin was because of too high dose of MPA relative to the dose of aglepristone, the delay of 14 days in obtaining tissues after aglepristone treatment, or simply an insufficient duration of aglepristone treatment requires further study.