Clinical and Endocrine Short-Term Effects of GnRH Analogue Deslorelin in Prepubertal Bitches: Does A “Flare-up” Occur?

Abstract

SummaryLong-acting GnRH agonists have been used both in canine estrus induction and prevention. The objective of the study was to investigate the clinical and endocrine short-term effects of a deslorelin implant (4.7 and 9.4 mg) in terms of initial "flare-up" in prepubertal bitches. Fourteen healthy, cross-breed prepubertal female dogs, aged 4 months, were used in the study. An implant containing 9.4 mg (G1, n=5) and 4.7 mg (G2, n=4) deslorelin (Suprelorin®) or a placebo (sodium chloride 0.9%, G3, n=5) was inserted subcutaneously. Estrus was monitored once daily by physical and sexual behavioral changes. Vaginal cytology, serum progesterone (P4) and estradiol 17β (E2) concentrations were monitored weekly for the first five weeks throughout the treatment. None of the bitches in the treatment (G1 and G2) and control (G3) group showed any signs of estrous throughout the study period. No local reactions were observed at the implantation site. Two bitches showed an increase in serum P4 concentrations (>1.0 ng/ml) in G1 (2/5; 40%), however, only one of these two animals (P4=6.37 ng/ml) showed an increase in serum E2 concentrations up to 37 pg/ml. No marked increase in serum P4 and E2 concentrations were observed during the first 13 weeks of treatment in G2. These data demonstrate that in prepubertal bitches, insertion of a deslorelin implant does not cause a "flare-up effect" which commonly occurs in anestrus adult bitches during the first month after implantation. However, further studies are needed to demonstrate that the "flare-up" effect of deslorelin implant in bitches especially during later prepubertal stages. Keywords: Prepubertal bitches, Suprelorin®, Flare-up effect Prepubertal Köpeklerde GnRH Analoğu Deslorelinin Kısa DönemKlinik ve Endokrinolojik Etkileri: "Flare-up" Gözlenir mi? ÖzetUzun etkili GnRH agonistleri köpeklerde hem östrusun uyarılmasında hem de baskılanmasında kullanılmaktadırlar. Bu çalışmada, pubertas öncesi dönemdeki dişi köpeklerde deslorelin implant (4.7 ve 9.4 mg) kullanımının "flare-up" dönemi olarak değerlendirilebilecek klinik ve endokrinolojik kısa dönem etkilerinin varlığı araştırılmıştır. Bu amaçla pubertas öncesi dönemde olduğu belirlenen ortalama 4 aylık yaşta on dört adet sağlıklı melez dişi kopek kullanıldı. Köpeklere deri altı yolla 9.4 mg (G1, n=5) ve 4.7 mg (G2, n=4) deslorelin (Suprelorin®) etken maddesi içeren implantlar ya da plasebo (sodyum klorür %0.9; G3; n=5) uygulandı. Östrus belirtileri günlük olarak fiziksel değişiklikler ve davranış değişiklikleri yönünden takip edildi. Ayrıca çalışma süresince vaginal sitoloji, serum progesteron (P4) ve östradiol 17β (E2) konsantrasyonları haftalık olarak izlendi. Tedavi (G1 ve G2) ve kontrol grubundaki (G3) hayvanların hiçbirinde östrus bulgusu belirlenmedi. İmplantın yerleştirildiği bölgede herhangi bir lokal yan etki gözlenmedi. Grup 1'de iki köpekte (2/5; %40) serum P4 düzeyinde bir artış gözlenirken, bu köpeklerden yalnızca birinde (P4=6,37 ng/ml) serum E2 düzeyinin 37 pg/ml'ye kadar yükseldiği belirlendi. Grup 2'de 13 haftal...

Suppression of Fertility in Pre‐pubertal Dogs and Cats

“…Body development was undisturbed in all bitches (Kaya et al. , ,b), as observed by others (Rubion et al. ) and in one study on pre‐pubertal ovariohysterectomy (Sontas and Ekici ).…”

“…; Kaya et al. , ,b). On the other hand, as indicated by an increased SCI in some pre‐pubertal bitches (Kaya et al.…”

“…(), none of the bitches showed clinical signs of oestrus and no flare‐up effect was observed (Kaya et al. , ,b). However, with the 9.4‐mg implant, two of five bitches showed an increase in E during the first 3 weeks after implantation, and one bitch obviously had ovulated (P4 > 6 ng/ml).…”

Pre‐pubertal treatment with a GnRH agonist in bitches—Effect on the uterus and hormone receptor expression

“…This was expected since uterine development should be finalized at the age of 4 months; uterine adenogenesis was reported to be completed at the age of 6‐8 weeks (Cooke et al., ). Furthermore none of the bitches showed any uterine disease which is important for their later breeding fitness; so far, no clinical abnormalities were seen after delay of puberty with GnRH agonists (Fontaine et al., ; Kaya et al., , , ; Marino et al., ; Rubion et al., ; Trigg et al., ).…”

“…Pre‐pubertal treatment with GnRH agonists has been reported in earlier studies; puberty could be successfully delayed in both male and female dogs and cats (Fontaine, Maenhoudt, Mir, Navarro, & Fontbonne, ; Kaya et al., , , ; Marino et al., ; Rubion et al., ; Trigg, Doyle, Walsh, & Swangchan‐uthai, ). Different preparations have been used and different dosages; azagly nafarelin 8.5 mg (Rubion et al., ) or mostly deslorelin 4.7 or 9.4 mg implants (Suprelorin ® , Virbac, F; Trigg et al., ; Fontaine et al., ; Marino et al., ; Kaya et al., ; Kaya et al., , ). The observed duration of effectiveness varied from 8 months to more than 24 months and it seems that it is not only dose dependent.…”