Remarks. The main drawback of this approach is that ferrets may fail to ovulate. Prolonged estrus can be expected, which may result
in bone marrow suppression. In male mice, immunization against LH receptor reduced androgen production.44 In male ferrets, this might reduce aggressive behavior and decrease the intensity of their musky odor. Again, some caution
is warranted because high LH receptor antibody titers in mice had an agonistic effect, resulting in hypertestosteronemia.44
Administering depot Gn-RH agonist
Principle. Depot Gn-RH agonists, such as leuprolide acetate and deslorelin, increase the concentrations of gonadotropic hormones; this
increase is followed by a desensitization of gonadotrope receptors, resulting in decreased LH and FSH plasma concentrations.45 The exact mechanism of the desensitization is still not clear.46
Method. Of the available formulations, leuprolide acetate (Lupron Depot 3.75 mg—TAP Pharmaceutical Products) is used to treat hyperadrenocorticism
in ferrets.11 Ferrets weighing less than 1 kg receive an intramuscular dose of 100 µg at monthly intervals, and ferrets heavier than 1
kg receive 200 µg per month. A similar treatment protocol might also be effective for contraceptive purposes. Slow-release
implants have been described in dogs,45,47 and a study with an implant containing the Gn-RH agonist deslorelin has been conducted in jills.48
Effect. The jills receiving a 4.7-mg deslorelin implant came into estrus within days after placement, but estrus ended within a week.
The ovarian activity of these ferrets was suppressed for more than a year.48 In addition, leuprolide acetate has induced estrus in dogs.49
Remarks. Slow-release Gn-RH agonist implants suppress reproductive function in dogs.47 Gn-RH implants might therefore be an option for use in hobs. Deslorelin implants are currently under investigation at Utrecht
University for their effectiveness in neutering hobs.
Administering Gn-RH receptor antagonist
Principle. Competitive Gn-RH receptor occupancy with Gn-RH receptor antagonists results in a decreased release of gonadotropic hormones
by the pituitary gland.46
Method. The available Gn-RH receptor antagonists have to be injected subcutaneously, but orally active nonpeptide Gn-RH antagonists
are being developed for use in people.50
Effect. The initial increase in gonadotropic hormones, seen with Gn-RH agonists, are not seen with Gn-RH receptor antagonists. The
use of these receptor antagonists will therefore result in an immediate decrease in gonadotropic hormone concentrations.
Remarks. Until now, only a few Gn-RH receptor antagonists have been registered for use in people.46 New and longer-acting drugs are being developed. Degarelix seems to be the most promising of these Gn-RH receptor antagonists.51 While older Gn-RH antagonists caused increased histamine release after injection, the newer drugs do not have this side effect.
Never theless, local reactions at the injection site are still common.46 These drugs seem to be promising for future prevention and treatment of hyper adreno corticism in ferrets.
Several potential methods exist, other than surgical neutering, to influence reproductive function in ferrets. Progestagens
seem practical and are already available for use in jills but need to be studied for use in hobs. Slow-release Gn-RH implants,
such as deslorelin, are already registered for use in animals in some countries and may become available for use in ferrets
within the next decade. Possible future alternatives may also be Gn-RH antagonists or immunization against Gn-RH. Detailed
studies are needed before these techniques can be recommended for neutering ferrets. Once these techniques become available,
it will be necessary to investigate whether they will actually reduce the incidence of hyperadrenocorticism in ferrets.
Nico J. Schoemaker, DVM, PhD, DECAMS, DABVP (avian practice)
Johannes T. Lumeij, DVM, PhD, DECAMS, DABVP (avian practice)
Ad Rijnberk, DVM, PhD, DECVIM
Department of Clinical Sciences of Companion Animals
Faculty of Veterinary Medicine
Yalelaan 8, 3584 CM Utrecht, The Netherlands
1. Bernard SL, Leathers CW, Brobst DF, et al. Estrogen-induced bone marrow depression in ferrets. Am J Vet Res 1983;44:657-661.