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be treated successfully with aglepristone21,22,23, which may be an option also for cats treated with long-acting progestogens. Dosages for mammary hypertrophy may need to be prolonged in time depending on whether it is a spontaneous disease or if it is due to progestogen administration4. Muphung et al 24 studied the effect of AGL in a group of queens treated with a high dose of medroxyprogesterone acetate (MPA - 50 mg) followed by 2 injections of 10 mg/kg AGL 3 weeks later. Based
on histology and immunohistochemistry, no evidence
of an effect of AGL on the mammary gland of treated queens was present 24. Lack of effect might be due to the very high dose of MPA used, to the rather low dose of aglepristone (10 mg/kg instead of 15 mg/kg), to the short treatment with AGL (only 2 injections) or to the long interval between MPA and AGL treatments.
ENDOCRINE INDICATIONS
Diabetes - Diabetes mellitus is a condition characterized by an altered carbohydrate metabolism due to an absolute deficiency of insulin, which is fairly common
in the canine, particularly in dogs of > 5 years of age 25. Neutered male and female dogs as well as intact (also pregnant) bitches are at a higher risk of developing
this condition. In diabetic dogs, insulin deficiency is typically paralleled by an increase in glucagon which, coupled with the decrease in peripheral use, causes hyperglycemia25. The action of insulin is modulated by a number of so called counter regulatory hormones (glucagon, glucocorticoids, catecholamine and growth hormone) responsible for reducing the effect of insulin at the cellular level26. Whenever a higher than normal concentration of these hormones is present in the general circulation for a prolonged period of time a normal amount of insulin will produce a lower biologic response 26. Such decreased response to insulin is referred to as insulin resistance, and it is generally suspected whenever hyperglycemia is present despite administration of single insulin doses higher than 1.0-1.5 IU/kg.
An increase in the concentration of the above
counter regulatory (or diabetogenic) hormones occurs whenever there is a) an inflammatory condition, b)
an endocrine disorder or c) following exogenous administration of one of the counter-regulatory hormones (i.e. glucocorticoids) or of other compounds which may raise their concentration, such as P4 26, 27.
In the bitch, endogenous or exogenous P4 can cause insulin resistance by stimulating the release of growth hormone (GH) from the mammary gland thus raising GH concentrations in the general circulation 27,28,29. While pituitary GH secretion is normally pulsatile, mammary GH secretion is not characterized by a pulse pattern and is not sensitive to stimulation and inhibition tests
30, the only exception being the capacity of being inhibited by the P4 antagonist AGL31. AGL binds to P4
receptors displacing P4 as well as progestogens from their binding sites, therefore it can be used to decrease clinical effects of high P4 concentrations directly as well as indirectly by causing a decrease in serum GH levels. A decrease in serum GH levels can be very important
in an intact diabetic bitch as soon as diestrus starts, because of the high production of ovarian progesterone characterizing the first 2-3 weeks of the canine luteal phase. The effectiveness of AGL in helping in the clinical management of diabetes in intact bitches was assessed in a group of 8 diabetic intact bitches of 9-15 yrs of age diagnosed as having a P4-induced insulin resistance complicating the management of their glycemia, with blood glucose levels remaining persistently higher than 200 mg/dl over 12 hour periods regardless of being treated with doses higher than 1.5 IU/kg BID of insulin32. These animals, whose serum P4 was higher than 5.0 ng/ ml at the beginning of the study, were treated with a 10 mg/kg dose of AGL on days 1, 2, 9 and 17, and compared to a control group of 6 diabetic intact bitches in which an equivalent amount of saline solution was administered on the same days of the treated bitches 32. Both groups of dogs received a porcine insulin zinc suspension treatment as appropriate in relation to their serum glucose concentrations. Glycemia was controlled on the day of treatment (day 0) and on days 5, 12 and 20 post- treatment. While no significant variation was observed in serum glucose levels at day 5, glycemia was significantly reduced at day 12 (when the average dose of insulin could be reduced to 0.8 IU/kg) and further on at day 20. Progesterone did not change between day 0 and 20, while GH showed a significant decrease in AGL treated bitches32. The use of AGL should always be considered when dealing with diabetic intact bitches in diestrus.
BIBLIOGRAPHY
1. Fieni F, Martal J, Marnet PG, Siliart B, Bernard
F, Riou M, Bruyas JF, Tainturier D – Hormonal variations in bitches after early or mid-pregnancy termination with aglepristone (RU534). J Reprod Fert Suppl 57: 243-248, 2001
· Schäfer-Somi S, Aksoy OA, Beceriklisoy HB, Einspanier A, Hoppen HO, Aslan
S. Repeated induction of abortion in bitches and the effect on plasma con- centrations of relaxin, progesterone and estradiol-17beta.Theriogenology. 2007 Oct 1;68(6):889-95.
2. Pettersson CH, Tidholm A. Safety and ef- ficacy of mid-term pregnancy termination using aglepristone in dogs. J Small Anim Pract. 2009 Mar;50(3):120-3. doi: 10.1111/j.1748- 5827.2008.00692.x.
· Gogny A, Fiéni F - Aglepristone: A review on its clinical use in animals. Theriogenology 85 (2016) 555–566
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43RD WORLD SMALL ANIMAL VETERINARY ASSOCIATION CONGRESS AND 9TH FASAVA CONGRESS











































































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