The use of a 4.7 mg deslorelin slow release implant in male dogs in the field

Dedication

Dedicated to my dear “doctoral father” and mentor Prof. Dr. Dr. h.c. mult. Bostedt! Thank you for your faith in me and for your long-term support! – Meinem Doktorvater und Mentor Prof. Dr. Dr. h.c. mult. Bostedt gewidmet. Danke für Ihr Vertrauen in mich und Ihre langjährige Unterstützung! Sandra Goericke-Pesch

Abstract

Objective Slow-release GnRH agonist implants (SRI) are used for reversible medical downregulation of testicular function in male dogs as an alternative to surgery. The 4.7 mg deslorelin SRI should reduce testosterone after 6–8 weeks and induce castration-like effects for 6 months (mon). However, some individual variation is described in the field in regard to onset and duration of effect. For this reason, we aimed to study the effects of the 4.7 mg deslorelin SRI in a larger cohort.

Material and methods In total 50 intact, healthy male dogs (12–48 months, mon; 9–40 kg) were treated with a 4.7 mg deslorelin SRI into the umbilical area (TG, n=45) or served as untreated controls (CG, n=5). CG dogs were surgically castrated after measurement of testicular dimensions and blood sampling for testosterone. In TG, SRIs remained for 5 mon in place and subsequently 3–7 male dogs were surgically castrated at removal (week, W 0) or 1, 2, 3, 4, 5, 6, 7, 8 or 10 weeks later. Examination parameters were testicular dimensions (before treatment, at 4, 8, 12 W, 5 mon, weekly until castration), testosterone (before treatment, at 8 W, 5 mon, castration) and testicular histology (castration).

Results Whereas examination parameters did not differ between CG and TG before treatment, testicular volume and testosterone was significantly reduced at all time points during treatment. In all but 3 (8 W) and 2 male dogs (5 mon) testosterone was basal during treatment before removal, whereas the parameters were significantly reduced compared to pre-treatment in the respective dogs. After implant removal, testosterone and testicular volumes increased. However, different to earlier studies, the „restart“ was more variable with individual basal testosterone until W7, but also physiological testosterone concentrations in W2. Similarly, histological testicular findings at castration were quite variable: besides an arrest on spermatogonia and spermatocytes, elongated spermatids with normal spermatogenesis were found in individual dogs.

Conclusion Our study confirms the efficacy of the deslorelin SRI, but also individual variation especially regarding reversibility of effects on endocrine and germinative testicular function.

Clinical relevance Deslorelin SRIs offer a suitable alternative to surgical castration with individual variation to be considered when used in clinical practice.

Zusammenfassung

Gegenstand und Ziel Slow release GnRH-Agonist Implantate (SRI) werden bei Rüden zur reversiblen medikamentösen Downregulation der Hodenfunktion als Kastrationsalternative eingesetzt. Das 4,7 mg Deslorelin SRI soll nach spätestens 8 Wochen zu einer signifikanten Reduktion von Testosteron führen und ca. 6 Monate (Mon) wirken. Dennoch ist eine gewisse individuelle Variabilität bezüglich Wirkeintritt und -dauer im Praxisalltag beschrieben, weshalb es unser Ziel war, die Effekte in einer größeren Kohorte zu untersuchen.

Material und Methoden Hierzu wurden 50 intakte, gesunde Rüden im Alter von 12–48 Mon mit einem Gewicht von 9–40 kg entweder mit einem 4,7 mg Deslorelin SRI in die Nabelregion injiziert (n=45, TG) oder dienten als unbehandelte Kontrollen (n=5, CG). Die Hunde aus CG wurden nach Erfassung der Hodenmaße und Blutentnahme für Testosteron kastriert. In TG wurden die Implantate für 5 Mon belassen und dann jeweils 3–7 Rüden nach Entfernung (Woche, W0) oder 1, 2, 3, 4, 5, 6, 7, 8 oder 10 Wochen danach kastriert. Untersuchungsparameter waren Hodenmaße (Messung 4, 8, 12 W, 5 Mon, wöchentlich nach Entfernung bis Kastration), Testosteron (Blutprobe 8 W, 5 Mon, Kastration) und Hodenhistologie (Kastration).

Ergebnisse Während sich die Untersuchungsparameter vorher zwischen TG und CG nicht unterschieden, waren die Hodenvolumina und Testosteron infolge der Behandlung zu allen Terminen signifikant reduziert. Bei allen außer 3 Rüden nach 8 W und 2 Rüden nach 5 Mon war nach Behandlung Testosteron basal, wobei auch bei diesen zu anderen Zeitpunkten Testosteron und Hodenvolumina reduziert waren. Nach Implantatentfernung kam es zu einem Anstieg von Testosteron und Hodenvolumina. Im Vergleich zu vorherigen Studien verlief der „Restart“ allerdings deutlich variabler mit vereinzelten basalen Werten bis W7, aber auch physiologischen Testosteronkonzentrationen bereits in W2. Dementsprechend variabel stellten sich die histologischen Hodenbefunde zum Kastrationszeitpunkt dar, neben Arresten auf Ebene von Spermatogonien und Spermatozyten waren bei anderen Hunden elongierte Spermatiden mit weitgehend normaler Spermatogenese nachweisbar.

Schlussfolgerung Die Studie bestätigt die Wirksamkeit des Deslorelin SRIs, aber auch die individuelle Variabilität, v. a. hinsichtlich der Reversibilität der Effekte auf die endokrine und germinative Hodenfunktion.

Klinische Relevanz Deslorelin SRIs bieten eine geeignete Alternative zur chirurgischen Kastration, wobei die individuelle Variabilität in der Praxis unbedingt berücksichtigt werden muss.

Key words

Hormonal castration - GnRH agonist slow-release implant - downregulation - infertility

Schlüsselwörter

Hormonelle Kastration - slow release GnRH-Agonist Implantat - Downregulation - Infertilität

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