Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-Agonist Azagly-Nafarelin as a removable implant “Gonazon”; a preclinical trial

Abstract

Downregulation of anterior pituitary GnRH-receptors by application of a slow release GnRH-implant offers an effective and reversible alternative to surgical castration of the male dog. Aim of the present study was to test the efficacy and the underlying mechanisms of a new non-biodegradable controlled-release device implant (Gonazon ®, Intervet, containing 18.5 mg of the GnRH-agonist Azagly-Nafarelin). Eight male beagle dogs were implanted s.c. at the para-umbilical region. In four dogs implant removal was after 180 days (group 1), in the other four dogs after 365 days (group 2). Eleven weeks after implantation availability of LH was reduced ( p < 0.0001) by 70%. After an initial increase lasting for about 4 days, testosterone (T) and estradiol (E2) concentrations decreased ( p < 0.0001) to basal levels within 17.5 ± 8.4 days. Size of testes was decreased by about 82% after 17 weeks, size of prostate by about 46% after 5 weeks ( p < 0.0001). Five to 7 weeks after implantation all dogs were aspermic. Testosterone and estradiol concentrations, together with testicular and prostatic size remained suppressed in all dogs in group 1 and one dog of group 2 until implant removal. The other three dogs of group 2 escaped from down-regulation between 223 and 324 days. Effects on the availability of LH, T, E2 and on testicular and prostatic size were fully reversible after implant removal or escape from down-regulation. In six dogs semen quality was back to pre-treatment values after about 29 weeks, however, one dog developed oligozoospermia while another one stayed azoospermic, probably due to an obstruction within the epididymal duct.