What Happens in Male Dogs after Treatment with a 4.7 mg Deslorelin Implant? I. Flare up and Downregulation

Simple Summary Until now, information about the “flare up” and the time to downregulation in male dogs after treatment with a 4.7 mg deslorelin implant is strongly limited, regarding testosterone concentrations, testicular and prostatic volume and semen quality. The aim of this study was to provide detailed insights into these open questions. GnRH and hCG stimulation tests were performed to gain further insights into testicular endocrine function. Seven male beagle dogs were treated with a 4.7 mg deslorelin implant, and three animals were treated with saline, representing the controls. In deslorelin-treated dogs, first basal testosterone concentrations were observed earliest on D7 and latest on D28 after treatment. Infertility—based on the lack of semen or spermatozoa— was diagnosed earliest on D35 and latest on D77. After five months, the treatment was still effective in six dogs but was reversed in one deslorelin-treated dog. Abstract Although registered since 2007, knowledge about changes in testosterone concentrations (T), testicular and prostatic volumes (TV, PV) and semen quality, as well as the time point of infertility following treatment with a 4.7 mg deslorelin (DES) slow-release implant, is limited. Therefore, seven sexually mature male dogs were treated with DES (TG); three male dogs treated with saline served as controls (CG). The study assessed local tolerance, TV, PV, semen parameters and T subsequent to GnRH/hCG stimulation in regular intervals. Local tolerance was good. In TG, T was increased right after treatment, but decreased four hours afterwards. Subsequently, TV, PV, semen quality and T decreased over time in TG, but not CG. T was basal (≤0.1 ng/mL) from D28 onwards. Response to GnRH/hCG stimulation was variable, with two TG dogs having increased T post-stimulation on all study days independent of pre-treatment concentrations. A(zoo)spermia in TG was observed from D35–D77 in all seven dogs. Whereas treatment was still effective in six TG dogs five months after implant insertion, it was fully reversed in one dog in terms of T and spermatozoa on the last examination. These results indicate high variation in individual dogs, necessary to consider when advising dog owners.

[1]  B. Somoskői,et al.  Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog. , 2021, Theriogenology.

[2]  W. Niżański,et al.  B-Mode and Doppler Ultrasonographic Findings of Prostate Gland and Testes in Dogs Receiving Deslorelin Acetate or Osaterone Acetate , 2020, Animals : an open access journal from MDPI.

[3]  S. Goericke-Pesch,et al.  [GnRH agonist implants in small animal practice - what do we know 13 years following EU registration?] , 2020, Tierarztliche Praxis. Ausgabe K, Kleintiere/Heimtiere.

[4]  W. Niżański,et al.  Comparison of Clinical Effectiveness of Deslorelin Acetate and Osaterone Acetate in Dogs with Benign Prostatic Hyperplasia , 2020, Animals : an open access journal from MDPI.

[5]  S. Romagnoli,et al.  Interval between Removal of a 4.7 mg Deslorelin Implant after a 3-, 6-, and 9-Month Treatment and Restoration of Testicular Function in Tomcats , 2020, Animals : an open access journal from MDPI.

[6]  A. Günzel-Apel,et al.  Rhodesian Ridgebacks have an increased risk to develop benign prostatic hyperplasia. , 2019, Reproduction in domestic animals = Zuchthygiene.

[7]  S. Goericke-Pesch,et al.  Expression of prostaglandin (PG) D synthase lipocalin and hematopoietic type and PG D receptor during restart of spermatogenesis following downregulation using a slow release GnRH agonist implant in the dog , 2019, Cell and Tissue Research.

[8]  S. Goericke-Pesch,et al.  Expression of PTGS2, PGFS and PTGFR during downregulation and restart of spermatogenesis following GnRH agonist treatment in the dog , 2018, Cell and Tissue Research.

[9]  M. R. Root Kustritz.  Population Control in Small Animals. , 2018, The Veterinary clinics of North America. Small animal practice.

[10]  G. Luvoni,et al.  Assessment of the age for a preventive ultrasonographic examination of the prostate in the dog. , 2017, Theriogenology.

[11]  C. Ambrósio,et al.  Immunolocalization of proteins in the spermatogenesis process of canine. , 2017, Reproduction in domestic animals = Zuchthygiene.

[12]  G. England,et al.  Digital image analysis of testicular and prostatic ultrasonographic echogencity and heterogeneity in dogs and the relation to semen quality. , 2015, Animal reproduction science.

[13]  S. More,et al.  Neutering of cats and dogs in Ireland; pet owner self-reported perceptions of enabling and disabling factors in the decision to neuter , 2015, PeerJ.

[14]  P. Čížek,et al.  Azoospermia with variable testicular histology after 7 months of treatment with a deslorelin implant in toms. , 2015, Theriogenology.

[15]  N. Santos,et al.  Suppression of fertility in adult dogs. , 2014, Reproduction in domestic animals = Zuchthygiene.

[16]  K. Failing,et al.  Status of the down-regulated canine testis using two different GNRH agonist implants in comparison with the juvenile testis. , 2013, Reproduction.

[17]  A. Troisi,et al.  Clinical efficacy of the GnRH agonist (deslorelin) in dogs affected by benign prostatic hyperplasia and evaluation of prostatic blood flow by Doppler ultrasound. , 2013, Reproduction in domestic animals = Zuchthygiene.

[18]  A. Wehrend,et al.  Basal testosterone concentrations after the application of a slow-release GnRH agonist implant are associated with a loss of response to buserelin, a short-term GnRH agonist, in the tom cat. , 2013, Theriogenology.

[19]  K. Failing,et al.  Retrospective analysis of canine semen evaluations with special emphasis on the use of the hypoosmotic swelling (HOS) test and acrosomal evaluation using Spermac(®). , 2013, Reproduction in domestic animals = Zuchthygiene.

[20]  S. Romagnoli,et al.  Semen quality and onset of sterility following administration of a 4.7-mg deslorelin implant in adult male dogs. , 2012, Reproduction in domestic animals = Zuchthygiene.

[21]  K. Failing,et al.  Restart of steroidogenesis in dogs during recrudescence of testicular function following downregulation with a GnRH-agonist implant , 2012, Cell and Tissue Research.

[22]  P. Čížek,et al.  Reversible suppression of sexual activity in tomcats with deslorelin implant. , 2012, Theriogenology.

[23]  B. Hoffmann,et al.  Development of semen quality following reversible downregulation of testicular function in male dogs with a GnRH agonist implant. , 2012, Reproduction in domestic animals = Zuchthygiene.

[24]  M. Wiltbank,et al.  Humoral immune response in lactating dairy cows after repeated exposure to human chorionic gonadotropin. , 2012, Theriogenology.

[25]  I. Reichler,et al.  [The use of deslorelin acetate (Suprelorin®) in companion animal medicine]. , 2012, Schweizer Archiv fur Tierheilkunde.

[26]  M. R. Root Kustritz,et al.  Effects of surgical sterilization on canine and feline health and on society. , 2012, Reproduction in domestic animals = Zuchthygiene.

[27]  A. Wehrend,et al.  Clinical efficacy of a GnRH-agonist implant containing 4.7 mg deslorelin, Suprelorin, regarding suppression of reproductive function in tomcats. Sandra.Pesch@vetmed.uni-giessen.de. , 2011, Theriogenology.

[28]  S. Arlt.  Die hormonelle Kastration von Rüde und Hündin – ein Überblick , 2010, veterinär spiegel.

[29]  M. Driancourt,et al.  Evaluation of the clinical efficacy of Gonazon implants in the treatment of reproductive pathologies, behavioral problems, and suppression of reproductive function in the male dog. , 2010, Theriogenology.

[30]  G. Martin,et al.  Dose-response studies for pituitary and testicular function in male dogs treated with the GnRH superagonist, deslorelin. , 2009, Reproduction in domestic animals = Zuchthygiene.

[31]  G. Martin,et al.  Morphological study of the effects of the GnRH superagonist deslorelin on the canine testis and prostate gland. , 2009, Reproduction in domestic animals = Zuchthygiene.

[32]  B. Hoffmann,et al.  Recrudescence of spermatogenesis in the dog following downregulation using a slow release GnRH agonist implant. , 2009, Reproduction in domestic animals = Zuchthygiene.

[33]  M. Driancourt,et al.  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. , 2009, Theriogenology.

[34]  A. Galatos,et al.  Comparison between ultrasonographic and caliper measurements of testicular volume in the dog. , 2008, Animal reproduction science.

[35]  G. Martin,et al.  Pituitary and testicular endocrine responses to exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone in male dogs treated with GnRH agonist implants. , 2007, Reproduction, fertility, and development.

[36]  J. Bryan,et al.  A population study of neutering status as a risk factor for canine prostate cancer , 2007, The Prostate.

[37]  G. Schuler,et al.  Samengewinnung, -konservierung und künstliche Besamung beim Hund , 2007, Tierärztliche Praxis K: Kleintiere/Heimtiere.

[38]  T. Trigg,et al.  A review of advances in the use of the GnRH agonist deslorelin in control of reproduction. , 2006, Theriogenology.

[39]  M. Kutzler,et al.  Non-surgical methods of contraception and sterilization. , 2006, Theriogenology.

[40]  B. Ducro,et al.  Incidence, risk factors, and heritability estimates of hind limb lameness caused by hip dysplasia in a birth cohort of boxers. , 2005, American journal of veterinary research.

[41]  T. Nett,et al.  Pituitary gonadotropin-releasing hormone (GnRH) receptor: structure, distribution and regulation of expression. , 2005, Animal reproduction science.

[42]  M. Amaku,et al.  Adoption of Shelter Dogs in a Brazilian Community: Assessing the Caretaker Profile , 2005, Journal of applied animal welfare science : JAAWS.

[43]  U. Kaiser,et al.  Regulation of gonadotropins by inhibin and activin. , 2004, Seminars in reproductive medicine.

[44]  G. Martin,et al.  Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs. , 2003, Reproduction, fertility, and development.

[45]  F. Shofer,et al.  Immunohistochemical characterization of canine prostatic carcinoma and correlation with castration status and castration time. , 2003, Veterinary and comparative oncology.

[46]  J. Schalken,et al.  Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs , 2002, Molecular and Cellular Endocrinology.

[47]  G. Martin,et al.  Use of a GnRH analogue implant to produce reversible long-term suppression of reproductive function in male and female domestic dogs. , 2001, Journal of reproduction and fertility. Supplement.

[48]  B. Hoffmann,et al.  Testicular endocrine function, seasonality and semen quality of the stallion. , 1999, Animal reproduction science.

[49]  L. Glickman,et al.  Host related risk factors for canine osteosarcoma. , 1998, Veterinary journal.

[50]  A. Mailles,et al.  Ultrasonographic evaluation of the prostate in healthy intact dogs. , 1998, Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association.

[51]  D. Horohov,et al.  Kinetics of the humoral immune response to multiple treatments with exogenous gonadotropins and relation to ovarian responsiveness in domestic cats. , 1996, American journal of veterinary research.

[52]  D. Horohov,et al.  Production of exogenous gonadotrophin-neutralizing immunoglobulins in cats after repeated eCG-hCG treatment and relevance for assisted reproduction in felids. , 1995, Journal of reproduction and fertility.

[53]  J. Roser,et al.  Effects of repeated hCG injections on reproductive efficiency in mares , 1990 .

[54]  AR Günzel-Apel,et al.  Dynamik der LH‐ und Testosteron‐Sekretion bei Beagle‐Rüden verschiedener Altersgruppen , 1990 .

[55]  L. M. Sanders,et al.  Use of potent LHRH analogues for chronic contraception and pregnancy termination in dogs. , 1989, Journal of reproduction and fertility. Supplement.

[56]  D. Noakes,et al.  The effect of age and season of the year on testicular function in the dog, as determined by histological examination of the seminiferous tubules and the estimation of peripheral plasma testosterone concentrations , 1982 .

[57]  G. Mcrae,et al.  Effect of chronic administration of a highly potent LHRH agonist on prostate size and secretory function in geriatric dogs , 1982, The Prostate.

[58]  A. Sundby,et al.  Plasma Concentrations of Testosterone in the Male Dog and Plasma Testosterone Profile Following Single Intramuscular Injection of HCG , 1981, Acta Veterinaria Scandinavica.

[59]  P. Cuatrecasas,et al.  Receptor-mediated internalization of fluorescent gonadotropin-releasing hormone by pituitary gonadotropes. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[60]  P. Torjesen,et al.  PLASMA LEVELS OF TESTOSTERONE IN BULLS , 1978 .

[61]  R. Falvo,et al.  Plasma concentrations of testosterone and LH in the male dog. , 1978, Journal of reproduction and fertility.

[62]  P. Torjesen,et al.  Plasma levels of testosterone in bulls. Response to repeated HCG injections. , 1978, Acta endocrinologica.

[63]  M. Pineda,et al.  Immunization of dogs against human chorionic gonadotropin. , 1974, American journal of veterinary research.

[64]  W. G. Parker,et al.  Duration of estrus and ovulation time in nonlactating mares given human chorionic gondotropin during three successive estrous periods. , 1973, Journal of the American Veterinary Medical Association.

[65]  F. A. Beach.  Coital behavior in dogs. VI. Long-term effects of castration upon mating in the male. , 1970, Journal of comparative and physiological psychology.