Nonsurgical methods of contraception in dogs and cats: Where are we now? - Veterinary Medicine
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Nonsurgical methods of contraception in dogs and cats: Where are we now?
A viable alternative to spaying and neutering for canine and feline population control is being intensively investigated. Here's a look at some possible future options.


Chemical castration

Neutersol, an intratesticular injection that contains zinc gluconate neutralized by arginine, causes testicular sclerosis and permanent sterility. It was the first drug approved by the Food and Drug Administration for sterilization of companion animals.16 It was approved for use in the United States in 2003 for puppies 3 to 10 months of age with testicles measuring 10 to 27 mm in width. The injection volume is based on testicular width. It has been used in larger adult dogs in an extralabel manner. Since 2005 it has not been available in the United States after the patent holder and marketing company discontinued their relationship.16

EsterilSol is an identical product available through Ark Sciences in Mexico.4 Infertile (Rhobifarma Indústria Farmacêutica), which contains zinc gluconate and DMSO (dimethylsulfoxide) for intratesticular injection, was launched in Brazil in March 2009.4

Neutersol has the advantages of being permanent after one administration and does not require general anesthesia.16 Outpatient clinics in the United States using Neutersol have been very successful.17 The product is appealing to owners who do not want their dogs to have surgery or who want their dogs to retain the "masculine" look and presence of testicles. Since there is no noticeable difference in testicular size in adult dogs treated with Neutersol, permanent identification such as microchipping or tattooing is necessary to indicate that the animal has been sterilized.17

A large field trial to evaluate Neutersol in 10,000 dogs was conducted in three states in Mexico.18 Some dogs experienced moderate pain in the first 12 hours after injection.18 In 2.6% of the dogs, severe ulcers developed at the injection site. The ulcers were related to poor injection technique, and the incidence decreased after veterinarians began using separate needles to draw up and administer the solution as well as separate sterile needles for each intratesticular injection in each dog.

In another study on Isabella Island of the Galapagos, 3.9% of 103 dogs given zinc gluconate developed necrotizing injection site reactions.19 By comparison, 3.4% of 58 dogs experienced wound dehiscence after surgical castration. The zinc gluconate reactions were more severe and required more extensive surgical repair than the traditional surgical complications. The dogs that experienced zinc gluconate reactions were large, mature dogs that received near maximum-volume doses.19


The goal of immunocontraception is to develop a vaccine against a target in the reproductive system. The vaccine would induce antibody formation, and the immunity would then suppress normal reproductive function. The current vaccine targets are the zona pellucida (ZP), Gn-RH, and the LH receptor. Extensive research has been conducted in the field of immunocontraception for humane control of wildlife overpopulation.20,21 Consequently, these strategies have been applied to population control of dogs and cats.

ZP vaccines

The ZP, a mucoprotein layer surrounding the oocyte, consists of three glycoproteins: ZP1, ZP2, and ZP3. Spermatozoa must bind to the ZP before fertilization can occur. Vaccines against ZP are, therefore, only effective in preventing pregnancy in females. Hormonal cycling is not affected. Continued reproductive behaviors may not be acceptable for free-roaming cats and dogs.

A porcine zona pellucida (pZP) vaccine has been effectively used in many wildlife species, including horses, deer, and elephants.20 However, single-dose pZP vaccines have not been effective in cats.22,23 A recent study in which cats were vaccinated with feline ZP subunits showed antibody production specific to feline ZP and lower conception rates compared with the control group.24

In dogs, recombinant dog ZP3 was conjugated to a diphtheria toxoid carrier to create a vaccine.25 It was effective at preventing pregnancy in three out of four bitches, but they required multiple immunizations intramuscularly to keep titers high. Further research is being performed in this area, including the development of a fusion protein of ZP3 and rabies virus glycoprotein expressed in insect cells as well as a DNA vaccine expressing the same fusion protein.26


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