A model for the study of cystic endometrial hyperplasia in bitches

The aims of this study were: (i) to establish a reliable model for the study of cystic endometrial hyperplasia in ovariectomized bitches; and (ii) to assess the roles of oestrogen and progesterone in the pathogenesis of irritant-induced cystic endometrial hyperplasia. Greyhound bitches (n = 15) were ovariectomized and divided into five groups (n = 3 per group). After 3-4 weeks, oestradiol benzoate (0.6-4.8 micrograms kg-1, i.m.) was administered twice a day for 12 days to the bitches in group 1, followed by progesterone (0.2-1.8 mg kg-1, i.m.) twice a day for 30-33 days. These dosages were chosen to mimic the plasma hormone concentrations of a normal oestrous cycle. A silk suture was inserted by laparotomy into the left uterine horn 12 days into the simulated dioestrus (determined by vaginal cytology) and necropsy was performed after a further 12 days. For groups 2-5, the silk suture was positioned at ovariectomy. After a further 3-4 weeks, these bitches were treated with progesterone (group 2: 1.8 mg kg-1 i.m. twice a day), oestradiol benzoate (group 3: 0.6-4.8 micrograms kg-1 i.m. twice a day), oestradiol benzoate and progesterone together (group 4: previous dosages) or vehicle (group 5). Necropsies were performed after 12-13 days of treatment. Cystic endometrial hyperplasia was induced in the suture-containing uterine horns of all bitches in groups 1 and 4, and in two bitches in group 2. Cystic endometrial hyperplasia did not develop in any control (no suture) uterine horns, or in either uterine horn of the bitches treated with either oestradiol only or vehicle. These results indicate that progesterone is necessary for the development of irritant-induced cystic endometrial hyperplasia and that oestradiol potentiates the effects of progesterone. The protocol used for bitches in group 1 would be a suitable model for further studies of the pathogenesis of cystic endometrial hyperplasia.