By Dr. Becker
An injectable sterilization product for male dogs containing zinc gluconate neutralized with arginine is scheduled for release in the U.S. by the end of this year under the brand name Zeuterin ("zinc neutering"). The product is already in use in Bolivia, Columbia, Mexico and Panama under another name.
The drug is effective for permanent sterilization of male dogs at least three months of age. Zeuterin has been approved by the FDA for use in dogs three to ten months of age and can be obtained only by licensed veterinarians who have received training from the drug's manufacturer, Ark Sciences, in how to perform the injections. The manufacturer believes the drug will be approved for use in dogs of any age over three months before the U.S. release date.
The drug functions as a spermicide and causes irreversible fibrosis of the testicles, which eventually atrophy and shrink in size, but remain visible. Dogs receiving the injection are tattooed in the groin area as proof they are sterile.
Product Launch Aimed at Shelters and Spay-Neuter Clinics Across the U.S.
Many shelters and spay-neuter facilities don't have the recovery space for animals after sterilization surgery. For those organizations, Zeuterin should save time, money and space.
The injections are done on an outpatient basis, no anesthesia is involved, and dogs can be released relatively quickly after the procedure. Shelters and spay-neuter programs can then transfer some of the resources formerly committed to neutering male dogs toward spaying females and other outreach programs.
Proponents of Zeuterin believe it is unlikely individual veterinary practitioners will immediately embrace the sterilization drug, simply because they are already equipped and trained to do surgical spays and neuters. In addition, at this time Ark Sciences is training only a limited number of private veterinarians to inject Zeuterin.
Pet owners who want to have their male puppy chemically sterilized can add their names to a waiting list, which will at some point trigger Ark Sciences to send an offer to their vet to get certified to inject Zeuterin. According to Ark Sciences, the waiting list will be worked on a first-come first-served basis when the product becomes available.
It's impossible to predict when Zeuterin might be widely available as an option for private vet practices and individual pet owners. Whenever that time comes, I think it's important to understand the potential risks and benefits of this method of sterilizing male dogs.
Technology Approved by FDA in 2003
The formulation of zinc gluconate neutralized by arginine was actually approved by the FDA in 20031. That same year the drug was produced by Pet Healthcare International and distributed in the U.S. by Addison Laboratories under the name Neutersol.
According to Ark Sciences, Addison Labs overestimated the demand for the drug and created too much inventory. Excess inventory expired in two years, Pet Healthcare International went unpaid, and production shut down. Addison Labs and Pet Healthcare ended their relationship in 2005.
Ark Sciences subsequently acquired all rights to the Neutersol technology and has been distributing the product in Mexico and three other countries under the name Esterilsol for the last four years. They have used the drug extensively in Mexico in dogs three months and older to further evaluate its effectiveness as a sterilization agent, as well as to refine and improve the injection technique.
How the Drug Works as a Sterilization Agent
According to the Alliance for Contraception in Cats and Dogs (ACC&D) in their April 2012 Product Profile and Position Paper2 on Zeuterin:
As with any medical intervention, safety and effectiveness depend upon proper administration. The exact mechanism of action is not known. The following is based on a description provided by Ark Sciences. The product should be administered as an intratesticular injection into the center of the testicle via the dorsal cranial portion of testicle, parallel to the longitudinal axis. After injection the compound diffuses in all directions from the center of the testis. In the concentration used, zinc gluconate acts as a spermicide and destroys spermatozoa in all stages of development and maturation. It results in permanent and irreversible fibrosis in the seminiferous tubules, rete testis and epididymis. This produces a reduction in the size and texture of the testicles and permanent sterilization. Testosterone production is reduced by 41-52%, and the endocrine feedback system remains intact. Zinc gluconate is absorbed and metabolized by the body within 72 hours after the injection.
Also, from the Ark Sciences FAQ web page3:
How is testosterone lowered by Zinc Gluconate neutralized with Arginine?
The dosage and concentration is designed to ensure Leydig Cells in the interstitial space of the testes survive the procedure. Stimulated by Luteinizing Hormone (LH) produced in the pituitary gland, the Leydig Cells continue to support testosterone-related metabolic activity and growth. In the absence of spermatogenesis, Sertoli cells stop communicating the need for testosterone to mature sperm cells. The pituitary gland detects this lowered demand and lowers the LH levels. Since LH levels determine how much testosterone is produced by the Leydig cells, overall testosterone levels are reduced by 41-52% for all dogs permanently.
Zeuterin Adverse Reactions
The 2003 FDA drug approval document includes a study of 270 male puppies injected with the chemical sterilant. The puppies were a combination of shelter animals and family pets.
The following reactions were noted:
Reactions Upon Injection Reaction Dogs Affected Vocalization 6 Kicking 1
Local Reactions Reaction Dogs Affected Scrotal Pain 17 Scrotal Irritation 3 Biting and Licking 2 Scrotal Swelling 2 Scrotal Dermatitis 2 Scrotal Ulceration 1 Scrotal Infection 1 Dry Scrotal Skin 1 Scrotal Bruising 1 Preputial Swelling 1 Scrotal Sore 1
General Reactions Reaction Dogs Affected Leukocytosis 2 Neutrophilia 17 Vomiting 12 Anorexia 11 Lethargy 6 Diarrhea 5
Another zinc gluconate sterilization study was done in the Galápagos Islands and published in 2008. It was conducted in a cooperative effort by the University of Florida, the ASPCA, and Animal Balance of San Francisco, and titled "Comparison of intratesticular injection of zinc gluconate versus surgical castration to sterilize male dogs."4 The following observation was made by the researchers:
Although the complication rate was similar for surgical and zinc-gluconate castration, the zinc-gluconate reactions were more severe. Surgical wound complications were treated by superficial wound debridement and resuturing. In contrast, zinc-gluconate reactions required antimicrobial treatment, orchiectomy, and extensive surgical debridement and reconstruction, including scrotal ablation in 2 dogs. These reactions occurred following administration by both experienced and novice individuals. All dogs made a full recovery following treatment of zinc-gluconate reactions and incisional dehiscences.
The authors of this study determined that proper injection technique is critical because injection or leakage into surrounding tissues can result in severe tissue damage. And while scrotal swelling and tenderness are common in the first days after injection, a more serious reaction is the development of scrotal ulcers or draining tracts in the scrotal or preputial area. The self-trauma that follows can be severe.
The researchers also observed that lesions aren't always restricted to the injection site, which could indicate the solution may spread beyond the target area.
Long-Term Side Effects
According to Ark Sciences, since 1999 when the initial clinical studies were performed, there have been no reports of long-term side effects.
I would just add here that whenever we manipulate nature sufficiently to stop procreation, there WILL be long-term side effects. This is true for spay/neuter, and any other method. We are just beginning to understand the lifelong implications of surgical removal of ovaries and testicles, yet spaying and neutering of cats and dogs has been a common practice for decades.
I'm certainly not against the sterilization of pets. I'm a proponent of assessing the risks and benefits of everything we do as guardians of the animals in our care.
You can read more about Zeuterin on the Ark Sciences FAQ page as well as the other documents linked in the references, below.
Once the product is widely available to private veterinary practitioners, if you're considering it, I recommend talking with your vet about the pros and cons of the procedure for your own dog.