Gonadotropin-Releasing Hormone (GnRH) Agonist Implants for Male Dog Fertility Suppression: A Review of Mode of Action, Efficacy, Safety, and Uses

Abstract

At present, only surgical sterilization is available for veterinarians and pet owners seeking suppression of fertility in male dogs, in most countries. An alternative contraceptive alternative approach is GnRH releasing implants that desensitize the pituitary to the stimulatory effects of GnRH and thereby block testicular function (testosterone and sperm production). Two GnRH agonists (deslorelin and azagly-nafarelin) have been researched in controlled release formulations for this purpose. A deslorelin-releasing biodegradable implant, marketed under the name Suprelorin ® , has been available in Australia and New Zealand since 2007, the European Union (EU) since 2008, and received regulatory approval in China and Mexico in late 2019. Two versions of the implant are available, one labeled for a minimum of 6 months of fertility suppression in male dogs, and the other for a minimum of 12 months in male dogs. Another GnRH agonist (azagly-nafarelin) was also included in a solid implant (Gonazon ®). Research results showed it delivered 6-months to 1 year of suppressed fertility; however, it is not commercialized. This review paper summarizes research on the mechanism of action for these technologies and compiles and interprets the research on efficacy and safety. New findings on usage of the deslorelin releasing implant in countries where veterinarians and pet owners have this option is shared. Research on off-label use of the product in male dogs is also reviewed. This review aims to aid in the evaluation of the deslorelin releasing implant as an adjunct or alternative for surgical sterilization of male dogs.

Double-Blind, Placebo-Controlled Trial of Cyproterone Acetate to Prevent Flare-Up Effect on Dogs Implanted With Deslorelin

“…A Freeman-Halton extension of the Fisher exact probability test for a two-rows by two-columns contingency table (see Table 4 above) was performed to examine the relation between the presence of a PFU (Yes/No) and the presence BFU (Yes/No) in the subjects. It showed that there was no significant association between these two variables ( p = 0.53), even though all of the ( 6 ) subjects experiencing a BFU effect also presented a PFU effect. Because of this very small number of subjects experiencing both a PFU and a BFU, no analysis on the temporal patterns of these two variables (see Table 5 below) were carried out.…”

“…Moreover, 67% ( 6 ) of the owners in each treatment group were satisfied (with a 7/10 or more evaluation considered as a positive evaluation).…”

“…In companion animals, the deslorelin implant (Suprelorin®, Virbac, Carros, France) is the most commonly used. Chemical castration is an ethically interesting alternative to surgical castration and can improve the dog immediate welfare because the implant is reported to induce the same positive effect as surgical castration with regard to aggression, fear and play behavior ( 3 ) while avoiding a general anesthesia and pain from the surgery ( 4 – 6 ). Moreover, in many cases, the veterinarian does not know if the orchiectomy will induce the change expected by the owners if the request is of behavioral nature.…”

Testicular Expression of Antioxidant Enzymes and Changes in Response to a Slow-Release Deslorelin Implant (Suprelorin® 4.7 mg) in the Dog

“…Short-term GnRH antagonist treatment in rats, which resulted in decreased serum testosterone levels but not in testicular atrophy, also decreased testicular CAT and GPx activities without affecting lipid peroxidation or SOD activities [ 59 ]. In dogs, the application of a slow-release deslorelin implant causes “desensitization” of pituitary GnRH receptors, thereby reducing the release of gonadotropins and gonadal steroid hormone production [ 2 , 4 , 8 , 9 , 11 , 12 ]. This decrease in LH concentrations in peripheral blood, as well as in the intratesticular testosterone production, may result in the suppression of the testicular antioxidant system, which could lead to the production of free radicals, and consequently, germ cell apoptosis and disrupted spermatogenesis.…”

“…The subcutaneous implant containing the slow-release gonadotropin releasing hormone (GnRH) superagonist deslorelin (Suprelorin ® 4.7 mg or 9.4 mg, Virbac, France) is extensively and mainly used for the temporary, reversible suppression of spermatogenesis in male dogs as an alternative to surgical neutering [ 1 , 2 , 3 ]. Its mode of action is based on deslorelin’s increased stability and high binding affinity to GnRH receptors in the anterior pituitary, thereby preventing the stimulatory actions of endogenous GnRH on follicle stimulating hormone (FSH) and luteinizing hormone (LH) production [ 2 , 4 ]. In male gonads, LH and FSH control spermatogenesis by acting on their respective receptors in the Leydig and Sertoli cells, respectively, resulting in steroid hormone production, germ cell proliferation and differentiation during normal spermatogenesis [ 5 , 6 , 7 ].…”