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Use of a Gonadotropin Releasing Hormone Agonist Implant

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Use of a Gonadotropin Releasing Hormone Agonist Implant Use of a Gonadotropin Releasing Hormone Agonist Implant Containing 4.7 mg Deslorelin for Medical Castration in Male Ferrets (Mustela putorius furo) Bulliot Christophe, DVM1 Mentré Véronique, DVM2 Berthelet Adeline, DVM3 Navarro Christelle, DVM4 Bidaud Alice, DVM4 1 Corresponding author: Clinique Vétérinaire Exotic Clinic, 38 rue Robert Cousin, 77176 Nandy, France. E-mail: [email protected] 2 Clinique Vétérinaire de la Patte d’Oie, 155 Bd Victor Bordier, 95370 Montigny les Cormeilles, France. E-mail: [email protected] 3 Clinique Vétérinaire Exotic Clinic, 38 rue Robert Cousin, 77176 Nandy, France. E-mail: [email protected] 4 Virbac, 13ème rue - LID, 06511 Carros, France. Conflict of interest: the study was funded by Virbac. KEY WORDS: Ferret, Deslorelin, tent, for medical castration. This study is the Gonadotropin, GnRH, medical castration first evaluation of a GnRH-agonist implant containing 4.7 mg deslorelin for medical ABSTRACT castration in male ferrets with an assessment Sterilization of ferrets (Mustela putorius of the duration of infertility over a 3-year furo) is a common practice. Male ferrets, follow-up. Twenty-nine intact male ferrets unlike females, don’t need castration for in rut were implanted and were used for medical reasons, but are frequently neutered tolerance evaluation. Infertility was assessed to prevent reproduction and reduce their in 27 ferrets by evaluating their testosterone musky odor and aggressive territorial behav- concentrations, testis size and musky odor. ior. The search for an alternative to surgical Our results indicated that infertility was in- castration is an important goal and challenge duced within 6 weeks post-implantation and in this species. The use of a gonadotropin that the suppression of fertility lasted at least releasing hormone (GnRH) agonist implant 16 months. No side effects related to the im- containing deslorelin in ferrets has been plant were reported. The 4.7 mg deslorelin documented in the literature as a treatment implant is a suitable alternative for surgical for adrenocortical disease and, to a lesser ex- castration in male ferrets. Intern J Appl Res Vet Med • Vol. 12, No. 1, 2014. 67 INTRODUCTION of a GnRH-agonist implant containing 9.4 Sterilization of male and female ferrets mg deslorelin in hobs for medical castration. (Mustela putorius furo) is a common prac- The first one, conducted by Schoemakeret tice in Europe, USA, and Australia. Female al (2008a), presented this use as an alterna- ferrets (jills) that don’t reproduce need to be tive to surgical castration for the manage- neutered because they may develop a hyper- ment of fertility. The second, conducted by estrogenism with a secondary pancytopenia Vinke et al (2008), presented the effect of and death in case of continuous estrus for a surgical and chemical castration on inter- long period (> one month) (Goericke-Pesch male aggression, sexual behavior and play & Wehrend, 2012, Proháczik et al, 2009). behavior in hobs. Male ferrets (hobs) do not need castration To the authors’ knowledge, the GnRH- for medical reasons, but are frequently agonist implant containing 4.7 mg deslo- neutered to prevent reproduction, reduce the relin (Suprelorin®, Virbac, Carros, France) musky odor produced by their sebaceous has never been evaluated for the medical glands and reduce aggressive territorial castration of privately owned male ferrets. behavior (Schoemaker et al, 2008a, Vinke et The aim of the study was thus to evaluate al, 2008). its efficacy for the suppression of fertility, The role of surgical neutering in the de- as measured by the reduction of testosterone velopment of hyperadrenocorticism in both concentration, testis volume and odor, and sexes has already been described. Schoe- its duration of action. A second objective of maker et al (2000) showed a correlation the study aimed to evaluate the tolerance of between surgical neutering and hyperadre- the 4.7 mg deslorelin implants in intact male nocorticism in ferrets regardless of age. The ferrets. mean interval between the age of neutering MATERIALS AND METHODS and the age at onset of hyperadrenocorticism This study was an open and multicentric in that study was 3.5 years. Hyperadrenocor- study which was performed in four veteri- ticism is due to the loss of negative feedback nary clinics in France from December 2010 from the gonads on the hypothalamus. to December 2013. The study was conducted A secondary increased concentration of in compliance with the Guideline on Good gonadotropins leads to a permanent stimu- Clinical Practices (VICH 2000). Owners lation of the adrenal glands. The resulting were properly informed about treatment hyperadrenocorticism is due to hyperplasia possibilities. or neoplasia of one or both adrenal glands The onset of the contraceptive effect (Chen et al, 2010, Chen et al, 2014). The was assessed by observation of the ferret be- use of a gonadotropin releasing hormone havior, blood testosterone dosage, and testis (GnRH) agonist implant containing deslo- measurement. The study ended upon return relin seems to be a safe and efficient way of sexual behavior or in December 2013. to control clinical signs associated with This study gave information on the onset of hyperadrenocorticism (Schoemaker et al, action, the duration of the infertility, and the 2008b, Lennox & Wagner, 2012, Wagner et tolerance of the product in male ferrets. al, 2005, Wagner et al, 2009). Animals Alternatives to surgical neutering have Privately owned, intact male ferrets under been proposed to avoid the occurrence of 3 years of age were included. The ferrets hyperadrenocorticism. did not have previous deslorelin implants, The fertility of female ferrets has been corticoid within the preceding 14 days, con- successfully controlled with implants con- comitant disorders, or chronic or progressive taining 4.7 mg of deslorelin (Goericke-Pesch disease. The ferrets were in good health & Wehrend, 2012, Proháczik et al, 2010). (confirmed by the clinical examination and Two previous studies evaluated the use 68 Vol. 12, No.1, 2014 • Intern J Appl Res Vet Med. the haematological and biochemical blood events and concomitant treatments since the analysis results at the first visit). last visit. Ferrets presenting with at least one of The following clinical parameters were the following criteria after administration of observed at each visit: deslorelin implant were withdrawn from the • general health (assessment of body study: condition, oral cavity, eyes, ears, skin • adverse event or concomitant dis- and coat, heart, lungs, lymph nodes order requiring an end to the follow-up and spleen, digestive system and mus- • concomitant disorder that may inter- culoskeletal system) fere with the testosterone dosage and/ • evaluation of the injection site of the or the behavioral observations deslorelin implant • concomitant treatments likely to • seborrhea interfere with the product efficacy • body weight evaluation • temperature • failure of compliance to the protocol • right testis width and length by the owner, at least one testosterone The observations by the owner of the dosage result missing, or sexual activity of their ferret were recorded • withdrawal of the owner’s consent. by the investigator at the time of the visits. Procedures At each visit, the sexual status of the ferret Study design was recorded as being in rut or not in rut by The first visit (V1) occurred during the win- the investigators based on these parameters: ter 2010-2011 (December 13th 2010 – April musky odor, seborrhea, urine marking, and 13th 2011). The second visit (V2) took place aggressiveness. 42 +/- 2 days after the V1 and the third visit The follow-up of each ferret ended upon (V3) was in June 2011 (Figure 1). Depend- return of sexual behaviour or in December ing on the date of V1, the V3 was between 2013 when the owners were called in order 67 and 198 days after V1 with an average of to assess the return to fertility. 138.14 days (approximately 4.5 months). Treatment At each visit, the investigators per- The implants used were a slow-release de- formed a clinical examination, took blood vice and contained 4.7 mg deslorelin acetate samples, recorded the right testis measure- (Suprelorin®, Virbac, Carros, France). ment, and checked for possible adverse The implants were subcutaneously Figure 1: Study design V: visit, D: day (*) : V2b was optional: if sexual behaviour was still observed at V2 and/or blood testosterone level had not decreased between V1 and V2, a new visit (V2b) was scheduled 2 weeks after V2. V1 : D0 Inclusion Clinical examination Blood sample Injection of 4.7 mg deslore- lin implant V2 : D42 + 2 days Clinical examination Blood sample V2b* (optional): D56 + 2 days Clinical examination Blood sample V3: June 2011 Clinical examination Blood sample Intern J Appl Res Vet Med • Vol. 12, No. 1, 2014. 69 placed in the scruff of Figure 2: Evolution of the right testis volume (cm3) over time. the neck (interscapular * p=5.63E-7 between V1 and V2, ** p=5.63E-7 between V1 space or to the right or left and V3, *** p=2.3E-5 between V2 and V3. side), using the implanting device provided with the implants. One implant per ferret was placed irrespec- tive of the weight of the animal. All ferrets but one were anesthetized with isoflurane (Forene, Abbott France SA, Rungis, France or Belamont isoflurane, Nicholas Piramal Limited, London, UK) to ensure a good implant injection. Blood collection At each visit, one blood were considered as being 13 ng/ml and sample of about 1.5-2 ml was collected in a plasma testosterone values below the LLOQ heparinized tube. If necessary the animals were considered as being 0.1 ng/ml. were anesthetized with isoflurane. Blood Statistics samples were collected from the jugular vein or the vena cava cranialis. The investigator All data were analyzed using the statistical gently shook the heparinized tube, filled in software Statgraphics Centurion XV. The the Samples Identification form and then Normal Probability Plot, the Shapiro-Wilks centrifuged the heparinized tube to obtain test, as well as the standard skewedness and plasma and put it into another tube.
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