Products
 

Castration Vs. Esterilsol            
(Assuming trained and experienced practitioners for both)  

Issue Castration Esterilsol Esterilsol Comment
Sterilization 100% 99.6% Permanent and irreversible
Testosterone 95% reduction 41-52% reduction Permanent reduction
Mating Behaviors May or may not suppress behaviors around females in estrus May or may not suppress behaviors around females in estrus Study underway to evaluate any differences in behavior suppression between castratoin and Esterilsol
Everyday Behavior Controversial [1] No studies yet Possible behavorial issues related to testosterone elimination and full anesthesia are expected to be less
Long Term Health Both positive and negative effects, depending on breed [2] Formal two and five year follow-ups showed no negative effects Health risks related to testosterone elimination are expected to be less
Full Anesthesia 1 in 1,849 healthy dogs die [3] Not needed Mild sedation recommended
Rate of abnormal complications 6.1% 1.1% Worst case in US clinical study (0.4%) is scrotal ablation and in rarer cases castration
Recovery 4-6 hours 5-10 mins Avoid excessive physical activity
Capital Investment Surgical Facility Table Investment in certification training required

Veterinarians

I'm a vet. How do I learn to use your product?

This product is only available to licensed veterinarians who are trained in the Zeuterin™ injection technique. Online training and wet labs are being scheduled around the United States. Please contact us if you are interested in being certified.  Only certified veterinarians are able to purchase the product.

How does Zeuterin™ neuter a male dog?

After the injection, the Zeuterin™ solution diffuses in all directions from the center of the testis. The specific concentration of Zinc (a targeted spermicide) used in our formula destroys spermatozoa in all stages of maturation in the seminiferous tubules and in the epididymis. The seminiferous tubules, which were replete with spermatozoa, are now emptied and collapse.

The dog's body increases blood flow and creates inflammation to heal. Within days, scar tissue (or fibrosis) from the healing process creates blockages in the seminiferous tubules, and more importantly, in the rete testis (the part of the testis that feeds the epididymis). All sperm must finally pass through these feeder tubules, which are now effectively closed as a result of the specific location of the injection. Zinc Gluconate and Arginine are absorbed and metabolized by the body. The male dog is now safely neutered for life. View sample histopathology slides that were used to confirm permanent sterility here.

Leydig cells (cells responsible for the endocrine function of the testes) survive the procedure. Hence, the endocrine function of the testes remains intact. Over time, the seminiferous tubules, rete testis, epididymis, and prostate all atrophy--reducing the size and changing the texture of testicles.

How is testosterone lowered by Zeuterin™?

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.  In the FDA study, Zeuterin™ treated dogs showed testosterone levels that were 41-52% lower than intact dogs.

What is the evidence that the procedure is virtually painless?

According to the results from the FDA study, pain management would have benefitted 2.6% of the dogs during injection and 6.3% post injection.  Most dogs did not show signs of pain during or after the procedure in the FDA study but proactive pain management is left at the discretion of the veterinarian.  During clinical trials, 270 dogs were injected and of those dogs six (2.2%) of the dogs vocalized during the injection and one (0.4%) dog kicked. It should be noted that only 66/270 (24%) of the dogs were sedated prior to injection. Post-injection pain was seen in 17 (6.3%) of the dogs, with most scrotal pain reported in the first two days post-injection.

Pain is either somatic or visceral. Testicle is a classic example of an organ sensitive to pressure-induced visceral pain. Afferent nerve endings have been identified in the testicular capsule in cats and dogs (Corona 1953). During testicular damage or when pressure is applied to the testis, the visceral pain experienced is believed to be due to a rapid stretching of the testicular capsule. There is interesting research on the topic of pain receptors present in the testis that is referenced here for all to consider:

The Testis, Volume 1, Development, Anatomy, and Physiology. Johnson AD, Department of Animal Science, University of Georgia, Athens Georgia, Gomes WR, Animal Reproduction Teaching and Research Center, The Ohio State University, Columbus, Ohio and Vandemark NL, Animal Reproduction Teaching and Research Center The Ohio State University, Columbus, Ohio, ed. Academic Press, New York and London, 1970; p. 80-81 Chapter 2, Subchapter 5. Hodson N. Nerves of the Testis, Epididymis, and Scrotum. Here is an excerpt:

"5. OTHER RECEPTOR ORGANS

Pain receptors are considered to be present in the tunicae testis and it would seem reasonable to suppose that, as in other solid organs, the acute pain experienced in testicular injury is due in part to stretching of the capsule.

Pain receptors are considered to be present also in the walls of blood vessels; they are stimulated by ischemia, which is interpreted as pain (Sweet, 1959).

There has been no work on receptors in the smooth muscle of the epididymis, but it is possible that distension-sensitive receptors are present like those described in the external muscle coat of viscera. These receptors are excited by both passive distension and active contraction of hollow viscera (Iggo, 1966). It is possible that ChE-positive fibers in the epithelium of the cauda epididymis may be similar to "flow" receptors, stimulated by movement along the lumen (Iggo, 1966)."

Does this sterilization procedure increase or decrease the risk for testicular or prostate cancer?

Long-term observations have shown no increase in risk for testicular cancer. However, no studies have been performed to evaluate if Zeuterin™ decreases the risk of testicular cancer. For prostate cancer, see A population study of neutering status as a risk factor for canine prostate cancer that concludes that surgically castrated dogs are at double the risk to get prostate cancer. To the extent such increased risks are related to virtual testosterone elimination caused by surgical castration, higher risk of such cancers are not expected after zinc neutering.

Does this procedure have any effect on behavior?

As with surgical castration, Zeuterin™ may or may not not eliminate male behavior such as roaming, marking, aggression, or mounting in dogs.

Some studies, not yet peer-reviewed, suggest a correlation between several undesirable behaviors in dogs that have been surgically neutered (See Behavioral and Physical Effects of Spaying and Neutering Domestic Dogs (Canis familiaris) by Parvene Farhoody in May, 2010 ). To the extent such undesirable behaviors seen in surgically neutered dogs are caused by the complete elimination of testosterone, Zinc Neutering would be unlikely to cause them.

What are the side effects?

While adverse reactions requiring medical treatment occurred in only 1.1% of the dogs, there were minor reactions observed in 6.3% of dogs during the FDA study. Local reactions included testicular swelling (normal reaction to the injection), pain (dogs may resist sitting or may sit with both hind legs open), biting and licking at the scrotum, swelling of the prepuce and irritation, dermatitis, ulceration, infection, dryness or bruising of the scrotum. Systemic reactions included an increase in the white blood cell count, vomiting, anorexia (loss of appetite), lethargy (tiredness or abnormal attitude), and diarrhea.

Most reactions were seen within the first 7 days after the injection. Over 93% of dogs did not show any signs of post procedure pain. When pain was detected, it was most commonly seen in the first 2 days. No pain management medications were used in the study. Vomiting was most commonly seen on the day of the injection (within 1 minute and 4 hours after the injection). It is recommended to withhold food for 12 hours prior to injection to help prevent vomiting, which occurred in 4% of dogs. Your dog's testicles may remain slightly enlarged but non-painful for a few months after the injection. Proper injection technique and owner observation post-injection is critical to avoid any potential undesirable side effects.

Are there any studies on long-term side effects?

Yes, we followed 40 dogs for over two years and have data on many of these dogs for over 5 years. Since 1999, when the initial clinical studies were performed, there have not been any reports of long-term side effects.

Does this sterilization procedure increase or decrease the risk for testicular or prostate cancer?

Long-term observations have shown no increase in risk for testicular cancer. However, no studies have been performed to evaluate if Zeuterin™ decreases the risk of testicular cancer. For prostate cancer, see A population study of neutering status as a risk factor for canine prostate cancer that concludes that surgically castrated dogs are at double the risk to get prostate cancer. To the extent such increased risks are related to virtual testosterone elimination caused by surgical castration, higher risk of such cancers is not expected after Zeutering.

What is the formula for Zeuterin™?

Zinc Gluconate (What is Zinc Gluconate? ) neutralized with L-Arginine (What is L-Arginine?) is the first compound ever to be approved by the FDA as safe for neutering. It uses Zinc Gluconate (a trace element) and Arginine (an amino acid), both of which are essential for the body. In fact, they are health supplements that millions of us use every day. Zeuterin™ does not contain any preservatives. 

What is the evidence that shows the procedure causes permanent sterility?

Normal spermatogenesis cycle is approximately two months in duration. Semen collected during the dosage titration study was evaluated and analyzed in accordance with Seager, S.W.J.: Semen Collection and Evaluation in the Dog. In: Current Therapy in Theriogenology, D.A. Morrow, Ed., W.B. Saunders Company, Philadelphia, PA, 1986; pp. 539-541. The dogs were careful monitored for 24 months post-injection with semen collection and analysis performed on a monthly basis. The criteria for semen evaluation are as follows:

Normal Semen Values:

  • Sperm concentration: 200-1000 X 106/ejaculate
  • Semen volume: 1-40 mL/ejaculate
  • Spermatozoa motility: >70% with progressive forward motility
  • Aspermia: No semen ejaculated
  • Azoospermia: No sperm in the ejaculate
  • Necrospermia: Sperm in the ejaculate are motionless/dead
  • Oligospermia: Sperm concentration less than 20 X 106 (for purposes of this field study)

During the dosage titration study, all of the dogs were sterile or infertile at each collection period.

To address permanency, seminiferous tubules could occupy as much as 90% of the volume of the testicle. The size of testicles decreased over time in all dogs in the clinical study pointing to increased fibrosis of the seminiferous tubules. Was it fibrosis and does the testis have the capacity to reverse fibrosis? To answer this question, it is necessary to understand the histopathologic evaluation of testis and epididymis at the end of the 24 months in the context of "End Points" (Slides). At the end of 24 months, the histopathology of the testis, the head of the epididymis, the body of the epididymis and the tail of the epididymis were performed to analyze the presence or absence of functioning sperm producing cells and seminiferous tubules. The histopathology showed that no normal seminiferous tubules existed and only fibrotic or nonfunctional seminiferous tubules were present throughout the testis. It should be noted that unfortunately or in this case fortunately the body does not reverse fibrosis and there is no known medicine or treatment to recover the fibrotic seminiferous tubules of the testis, which renders the animal permanently sterile-a claim that the FDA has approved based on the evidence presented.

In the Histological and histopathological evaluation of the testis, Russell, L. D., A. P. S. Hikim, R. A. Ettlin, and E. D. Clegg. 1990.1st ed. Cache River Press, St. Louis, Mo., Chapter 7: Histopathologic Evaluation of the Testis in Toxicologic Testing and Risk Assessment discusses the histologic evaluation of the testis is an important component of many regulatory agency test protocols. Histopathologic evidence may reveal disruption in testicular tissue, particularly in the seminiferous epithelia, and may be used as the basis for regulatory action. The textbook provides a variety of end points to measure qualitative and quantitative analysis of reproductive viability.

Some of the measures that have served as end points in toxicology are listed below:

  • End Points for Histopathologic Examination of the Seminiferous Epithelium
  • Presence of degenerating, sloughed and/or infiltrating cells
  • Absence of a tubular lumen
  • Absence of elongated spermatids
  • Most advanced cell type present
  • Height of germinal epithelium
  • Tubule diameter
  • Evaluation of each stage for damage or lack of component cell types ("staging")
  • Number of spermatids/tubular cross section
  • Number of germ cells/Sertoli cell nucleus (specific cell type)
  • Number of germ cells/Stage 1, VII, or VIII cross section (relative or absolute; specific cell type)

Histopathology slides of animal's testes and epididymis show a vast difference in the structure of the treated animal versus control.

How is it different from chemical castration in the past?

Historically, many hazardous chemicals (e.g., Calcium Chloride in Lidocaine or 90% alcohol, Chemcast) have been used on male mammal testicles, including dogs and cats. The objective is in this case is to actually dissolve the entire testis (chemical castration), making it equivalent to castration. None of these methods has ever been approved by the FDA as safe and effective and many have known to cause serious adverse reactions. None of these methods spare the endocrine function of the testicle like Zeutering does to maintain the testosterone needed for metabolic activities.

Are there any case studies on your products?

Yes. Here is a compilation of some reports that have been published ( NEUTERSOL: A CLINICAL PERSPECTIVE, James R. Weedon, DVM, MPH, DACVPM, Spay-Neuter Assistance Program, Inc., Houston, TX )

Do you have to be a licensed veterinarian to neuter using your product?

More than that, it must be administered by a veterinarian or a vet tech under the supervision of a licensed veterinarian. Further, each vet or vet tech must be certified by Ark Sciences prior to administering Zeuterin™.

Why do you have such a strict training and data collection protocol? Is the procedure prone to errors?

No. Once the vet is trained, errors are uncommon. Adverse reaction rates in the FDA study and in field trials are substantially lower than castration even without a tight training protocol. It became clear from our FDA study and other field experiences that even the low 1.1% adverse reaction rate (ones that required medical treatment) could be reduced if the injection technique is well understood and followed. Improvements from 90% to 99% are much easier than going beyond 99%--hence our intense focus on the procedure and data collection to get real-time feedback. Our goal is to create the best track record of our procedure--as each and every dog is important to us.

How do you identify a treated dog?

Leading microchip companies are capable of keeping neutering status in their databases. Tattooed serial numbers can also be used if a microchip is not practical. This will prevent the dog from being castrated if rescued at a later date.

During training, trainees are shown how to include an optional "Z" tattoo next to the scrotal area. It is usually formed using a tattoo pen next to the scrotum. Since this is the most invasive part of the entire procedure, pain management is needed to keep the dog comfortable.. Veterinarians familiar with Zeuterin™ will also be able to tell if a dog has been neutered after a few months by palpating the testicles--the testicles become smaller and firmer as scar tissue forms over time.

Many dog owners are understandably concerned about onlookers and "dog run" friends giving them the evil eye--assuming their anatomically correct male dog is intact. To address this concern, we will offer on-collar add-ons and fun T-shirts for Zeutered, but not castrated, dogs to flaunt their special status.

When does the dog become sterile?

The neutering procedure effectively shuts down sperm production within 1 to 3 days. However, sperm in the vas deferens and possibly the epididymis can reside for up to 30 days. The sperm maturation cycle is 60 days. Hence, a sexually mature Zeutered dog needs to be kept away from a female up to 60 days post injection. Note that vasectomies and surgical castrations can leave some sperm in the vas deferens remnants for up to 21 days.

What happens physically to the testicles?

During the procedure, a single injection of Zeuterin™ is administered directly into each testicle. Following the procedure, over time, the testicles generally shrink and change texture due to fibrosis.

What age should the dog be for the procedure?

Zeuterin™ is currently U.S. FDA approved for dogs 3-10 months old and testicle widths in the range of 10-27mm.

What is Ark Sciences doing to promote humane treatment of animals?

Ark Sciences is a social entrepreneurship venture. It is a mission-based private company founded by Joe Tosini, an ordained minister, to honor his commitment to making a difference in the world. He has chosen Ark Sciences and the vast potential of its technology, as the medium to achieve one of his missions: to alleviate the suffering of animals and humans.

end faq


Clinics & Shelters

I'm a low cost spay/neuter clinic. What is the best way to get started?

Training for the veterinarians is always step one. After that, Ark Sciences will put you in touch with other spay/neuter clinics that have implemented Zeutering for ideas on the most efficient way to incorporate the procedure in your clinic. Please contact us if you are interested in getting started.

Why is Ark Sciences targeting non-profits?

A very small number of the 25 million intact male dogs in the U.S. belong to breeders and dog professionals. There are a lot of barriers that deter dog owners from surgical neutering today, including anesthesia risk, cost, access, issue with mutilation/testis removal, long term health concerns, and unpredictable behavior changes. Animal welfare organizations have the mission and the experience in organizing outreach efforts to create awareness and increase neutering rates where it matters most. While organizations are free to choose their neutering methods, substituting one million castrations with Zeutering among non-profits could save tens of millions of donated funds every year. Imagine the potential windfall of that money becoming readily available for other animal welfare programs including dog adoption, responsible breeding, and pet education. The Ark Sciences executive team believes this to be an effective way to launch the company's mission and to educate the market on a promising new approach to address the problem of euthanizing healthy, adoptable pets.

Is Zeuterin™ more expensive than surgical castration?

Based on the Ark Sciences' potential offer to non-profits in the U.S., the cost of Zeuterin™ will approximately match the cost of consumables for surgical neutering. Given that Zeutering will take less time to perform and, based on results during clinical trials, requires less follow-up medical treatment than castration, it should save the clinic to incorporate this option into its protocol. As a neutering best practice, the real value of Zeutering becomes apparent when one considers the dog's safety (1 in 601 dogs die from anesthesia complications), long-term health, and behavior.

When does the dog become sterile?

The neutering effectively shuts down sperm production within 1 to 3 days. However, sperm in the vas deferens and possibly the epididymis can reside for up to 30 days. The sperm maturation cycle is 60 days. Hence, a sexually mature zinc neutered dog needs to be kept away from a female up to 60 days post injection. Note that vasectomies and surgical castrations can leave some sperm in the vas deferens remnants for up to 21 days. Zeuterin™ is FDA approved for permanent and irreversible sterilization with 99.6% effectiveness, as observed in the FDA approval study.)

How do you identify a treated dog?

Leading microchip companies are capable of keeping neutering status in their databases. Tattooed serial numbers can also be used if a microchip is not practical. This will prevent the dog from being castrated if rescued at a later date. During training, trainees are shown how to add an optional "Z" tattoo next to the scrotal area. It will be formed using a tattoo pen next to the scrotum. Since this is the most invasive part of the whole sterilization procedure, we will analyze the results to see if this method will survive as a standard practice. Veterinarians familiar with the sterilization procedure will also be able to tell if a dog has been sterilized after a few months by palpating the testicles--the testicles become smaller and firmer as scar tissue forms over time. Many dog owners are understandably concerned about onlookers and "dog run" friends giving them the evil eye--assuming their anatomically correct male dog is intact. To address this concern, we will offer on-collar add-ons and fun T-shirts for sterilized but not castrated dogs to flaunt their special status.

What kind of follow up care would be needed?

With over 4,000 dogs Zeutered since 2012, Ark Sciences has reports of 28 scrotal ulcerations. Timely intervention is important. A 72-hour check-in with the owner is recommended to make sure there are no initial signs of an ulceration. Limiting the number of physical check-ups needed is often achieved successfully by pre-screening over the phone or by getting a picture from dog owners' smart phones. We have no documented cases of dogs dying from the procedure and all cases of ulcerations were treated successfully, either by antibiotics or scrotal ablation.

What are the side effects?

While adverse reactions requiring medical treatment occurred in only 1.1% of the dogs in the FDA clinical trials, there were minor reactions observed in 6.3% of dogs. Local reactions included testicular swelling (normal reaction to the injection), pain (dogs may resist sitting or may sit with both hind legs open), biting and licking at the scrotum, swelling of the prepuce and irritation, dermatitis, ulceration, infection, dryness or bruising of the scrotum. Systemic reactions included an increase in the white blood cell count, vomiting, anorexia (loss of appetite), lethargy (tiredness or abnormal attitude), and diarrhea. Most reactions were seen within the first 7 days after the injection. Over 93% of dogs did not show any signs of post-procedure pain. When pain was detected, it was most commonly seen in the first two days. No pain management medications were used in the study. Vomiting was most commonly seen on the day of the injection (within 1 minute and 4 hours after the injection). It is recommended to withhold food for 12 hours prior to injection to help prevent vomiting, which occurred in 4% of dogs. Your dog's testicles may remain slightly enlarged but non-painful for a few months after the injection. Proper injection technique and owner observation post-injection is critical to avoid any potential undesirable side effects.

Does this procedure have any effect on behavior?

As with surgical castration, Zeuterin™ may or may not eliminate male behavior such as roaming, marking, aggression, or mounting in dogs. Anecdotal information collected from dog owners shows that Zeutering does suppress mating behaviors very much like castration. Formal statistical evidence is not there. Some studies, not yet peer-reviewed, suggest a correlation between several undesirable behaviors in dogs that have been surgically neutered (See Behavioral and Physical Effects of Spaying and Neutering Domestic Dogs (Canis familiaris) by Parvene Farhoody in May, 2010 ). To the extent such undesirable behaviors seen in surgically neutered dogs are caused by the complete elimination of testosterone, Zeutering would be unlikely to cause them.

Does Zeuterin™ increase or decrease the risk for testicular or prostate cancer?

Long-term observations have shown no increase in risk for testicular cancer. However, no studies have been performed to evaluate if Zeuterin™ decreases the risk of testicular cancer. For prostate cancer, see A population study of neutering status as a risk factor for canine prostate cancer that concludes that surgically castrated dogs are at double the risk to get prostate cancer. To the extent such increased risks are related to virtual testosterone elimination caused by surgical castration, higher risk of such cancers is not expected after Zeutering.

What happens physically to the testicles?

During the procedure, a single injection of Zeuterin™ is administered directly into each testicle. Following the procedure, over time, the testicles generally shrink and change texture due to fibrosis.

What age should the dog be for the procedure?

Zeuterin™ is currently U.S. FDA approved for dogs 3-10 months old and testicular widths in the 10-27mm range.

How does Zeuterin™ sterilize a male dog?

After the injection, the Zeuterin™ solution diffuses in all directions from the center of the testis. The specific concentration of Zinc (a gentle spermicide) used in our formula destroys spermatozoa in all stages of maturation in the seminiferous tubules and in the epididymis. The seminiferous tubules, which were replete with spermatozoa, are now emptied and collapse. The dog's body increases blood flow and creates inflammation to heal. Within days, scar tissue (or fibrosis) from the healing process creates blockages in the seminiferous tubules, and more importantly, in the rete testis (the part of the testis that feeds the epididymis). All sperm must finally pass through these feeder tubules, which are now effectively closed as a result of the specific location of the injection. Zinc Gluconate and Arginine are absorbed and metabolized by the body. The male dog is now safely sterilized for life. View sample histopathology slides that were used to confirm permanent sterility here. Leydig cells (cells responsible for the endocrine function of the testes) survive the procedure. Hence, the endocrine function of the testes remains intact. Over time, the seminiferous tubules, rete testis, epididymis, and prostate all atrophy--reducing the size and changing the texture of testicles.

How does Zeuterin™ lower testosterone?

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 the Leydig cells produce, overall testosterone levels are reduced by 41-52% for all dogs permanently.

What is the evidence that the procedure is virtually painless?

During the clinical trials 270 dogs were injected and of those dogs only 6 (2.2%) of the dogs vocalized during the injection and 1 (0.4%) dog kicked. It should be noted that 66 (24%) of the dogs were sedated prior to injection. Post-injection pain was seen in 17 (6.3%) of the dogs, with most scrotal pain reported in the first two days post-injection.

Are there any studies on long-term side effects?

Yes, we followed 40 dogs for over two years and have data on many of these dogs for over five years. Since 1999, when the initial clinical studies were performed, there have not been any reports of long-term side effects.

What is the formula for Zinc Neutering?

Zinc Gluconate (What is Zinc Gluconate? ) neutralized with L-Arginine (What is L-Arginine? ) is the first compound ever to be approved by the FDA as safe for neutering. It uses Zinc Gluconate (a trace element) and Arginine (an amino acid), both of which are essential for the body. In fact, they are health supplements that millions of us use every day. Zeuterin™ does not contain any preservatives. Simply discard any unused product 10 hours after first needle insertion into the vial to avoid complications due to possible product contamination.

How is it different from chemical castration in the past?

Historically, many hazardous chemicals (e.g., Calcium Chloride in Lidocaine or 90% alcohol, Chemcast) have been used on male mammal testicles, including dogs and cats. The objective is in this case is to actually dissolve the entire testis (chemical castration), making it equivalent to castration. None of these methods has ever been approved by the FDA as safe and effective and many have known to cause serious adverse reactions. None of these methods spare the endocrine function of the testicle like Zeutering does to maintain the testosterone needed for metabolic activities.

Are there any case studies on your products?

Yes. Here is a compilation of some reports that have been published ( NEUTERSOL: A CLINICAL PERSPECTIVE, James R. Weedon, DVM, MPH, DACVPM, Spay-Neuter Assistance Program, Inc., Houston, TX )

Do you have to be a licensed veterinarian to sterilize using your product?

More than that, a veterinarian or a vet tech under the supervision of a licensed veterinarian must administer it. Further, each vet or vet tech must be fully trained by Ark Sciences prior to administering Zeuterin™.

Why do you have such a strict training and data collection protocol? Is the procedure prone to errors?

No. Once the vet is trained, errors are uncommon. Adverse reaction rates in the FDA study and in field trials are substantially lower than castration even without a tight training protocol. It became clear from our FDA study and other field experiences that even the low 1.1% adverse reaction rate (ones that required medical treatment) could be reduced if the injection technique is well understood and followed. Improvements from 90% to 99% are much easier than going beyond 99%--hence our intense focus on the procedure and data collection to get real-time feedback. Our goal is to create a near perfect track record of our procedure as each and every dog is important to us.

Will the dog look intact after the procedure?

Yes. Cosmetic testicular implants like Neuticles should not be needed or used.

Why do adverse reactions (beyond side effects) occur in 1.1% of treated dogs?

There are some misconceptions about this procedure being "dangerous" and that Zinc Gluconate and Arginine create some acid-like deadly combination. The truth is that this combination has the same pH as water (i.e. 7), will not irritate normal skin, and 98.9% of dogs did not need any medical attention after the procedure during the FDA study. The adverse reactions have several causes:

Undetected scrotal dermatitis during the screening exam (sometimes hidden by thick scrotal fur because it is not shaved) combined with even a small product spill during the injection.

Fast injection speed leading to testis contraction, creating product spill into the scrotum.

Improper site entry or needle size leading to product diffusion outside the testis.

Incorrect dosage determination leading to product diffusion outside the testis.

Improper disinfection of the scrotal area or needle contamination leading to introduction of harmful bacteria into the testicle.

Improper after care or trauma to the testicle.

Testicular abnormalities or a rare allergic reaction to ingredients may also be possible causes.

Any of these issues can cause an itch or irritation in the testicle or scrotum causing the dog to lick and bite, as there is no E-collar in place after sterilization. If the dog is not monitored to prevent the licking and biting, serious irritation, infections, and/or ulcers can result. Most of these conditions can be treated with antibiotics and topical ointments. In some instances, scrotal ablation or castration may become necessary. In free roaming or poorly maintained dogs (depending on the shelter), scrotal dermatitis is more common, and after care may not be possible; rate of adverse reactions and severity is documented to be higher in these populations. In such instances, dogs that are not surgery candidates may well be rejected for Zeutering as well. In disease-prone areas, proper disinfection and follow-up protocols must be meticulously followed. As new organizations embark on zinc neutering, they should expect to treat one scrotal ulceration needing scrotal ablation and possible castration for every 100 dogs. Most scrotal irritations observed during the first three days heal on their own unless the dog starts to lick and/or bite the area and creates an infection. Experience shows that there may be a learning curve for vets in handling these adverse reactions effectively. A hot line is available for support and record keeping. 

How do I minimize adverse reactions?

To minimize the occurrence of adverse reactions, such as scrotal irritation, inflammation or infection, it is critical that you closely monitor your dog's activity post-injection and that you take all precautions necessary to prevent injury to the testicles and to prevent your dog from licking or biting the scrotal area. Restrict your dog's exercise to leash walking; not allow your dog to run, jump, or engage in play activity; not allow your dog to lay on hard or wet surfaces; not allow your dog to lick or bite the scrotal area.

When do I to choose non-surgical Zeutering over castration?

One is advised to understand the pros and cons of surgical neutering to make an informed decision (See peer reviewed referenced articles on Advantages and Disadvantages of surgical neutering on Wikipedia) For dog breeds more susceptible to complications from anesthesia (e.g., brachycephalic breeds like Pugs, Pekingese, Bulldog, etc.) or for dogs compromised in any way and at higher risk of anesthesia death Zeutering may well be the only humane option. (See The risk of death: the Confidential Enquiry into Perioperative Small Animal Fatalities in which one hundred and seventeen centers participated in the study between June 2002 and June 2004. During that time, 98,036 dogs, 79,178 cats and 8,209 rabbits were anesthetized or sedated and 163, 189 and 114 anesthetic-related deaths were identified respectively, resulting in risks of death of 0.17% in dogs, 0.24% in cats and 1.39% in rabbits). In the hands of an experienced practitioner, a non-invasive Zeutering injection is faster, gentler, safer, and cheaper than castration. Zeuterin™ will sterilize the dog and eliminate testosterone needed to support spermatogenesis, while preserving testosterone needed for other metabolic functions, a roughly 41-52% permanent reduction. While retaining some testosterone has beneficial effects, this procedure may not reduce the risks of diseases associated with male hormones, such as testicular (tumor rates are 7% but rate of metastatic testicular cancer is less than 1% overall) or perianal tumors (uncommon, as only 2% of all skin tumors are peri-anal but rate of metastasis is over 50%) in dogs. Studies show that for many dog breeds and individual dogs with genetic predispositions, surgical castration may compromise long-term health (See Long-Term Health Risks and Benefits Associated with Spay / Neuter in Dogs Laura J. Sanborn, M.S., May 14, 2007 ) If such long-term risks related to surgical castration are due to near elimination of testosterone in the body, they are unlikely to manifest after zinc neutering. It is widely accepted that neutering suppresses mating behaviors to varying degrees and also that there are no guarantees. However, there is emerging evidence that surgical castration may negatively impact dog behavior that is not mating related (e.g., fear, anxiety, trainability, etc.). To the extent such undesirable behaviors are the result of testosterone elimination, Zeutering is unlikely to manifest them.

What is the connection between Neutersol and Esterilsol™?

Neutersol and Esterilsol™ use the same mineral compound (Zinc Gluconate neutralized by Arginine) Neutersol is approved by the U.S. FDA as safe and effective for use in 3-10 month dog sterilizations. Neutersol was distributed by Addison Labs starting in 2003 for about two years. Ark Sciences acquired all rights to the Neutersol technology. Esterilsol™ is Ark Sciences' product for international markets. Esterilsol™ is now registered in four countries and pending approval in key markets around the world. It is approved for all dogs over three months of age in Mexico. Over the last four years, Ark Sciences has utilized Esterilsol™ extensively in Mexico in dogs three months and older to assess its efficacy as well as refining and improving the injection technique to minimize reactions. In early 2011, Ark Sciences having acquired full rights to the intellectual property for Neutersol, set up manufacturing at a facility located in the U.S. Ark Sciences' initial focus will be on non-profit animal shelters and high volume spay/neuter clinics.

What happened to Neutersol?

Encouraged by the enthusiastic response and media attention in 2003, Addison Labs, the exclusive distributor of Neutersol, overestimated the growth in demand and created too much inventory on credit. The excess inventory expired in two years and the manufacturer went unpaid, shutting down production. Finally, the manufacturer severed its relationship with the distributor.

Why did you develop a product only for males?

Dr. Min Wang, the co-inventor, wanted to come up with a solution that did not create system-wide reactions or imbalance.  The objective eliminated most approaches that can usually be applied to both males and females. The localized effect of Zinc targeted at sperm cells, and sperm cells along, makes it a safe and permanent sterilant.

Is there any way to verify that the procedure has been done correctly? 

Efficacy rate at the FDA trial was documented at 99.6% (about the same as a perfectly taken pill) so the dog is considered neutered after the procedure and a sterilization certificate is provided. If desired, sterilization of the dog can be verified by viewing the dog semen under a microscope after 30 days.

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Dog Owners

What should I learn before asking my vet to consider Zeutering my male dog?

The first step is to learn everything you can about the product and procedure and share what you have learned about Zeuterin™ and Zeutering with your veterinarian. Ask him or her to research the product and procedure if they don't already know about it. Once your veterinarian has learned more, ask him or her about the pros and cons of the procedure. Also, ask if he or she is certified to do the procedure.

My dog is an important part of my family and I carefully consider any medical procedure for my pet as I do for other family members. Why should I consider Zeutering as a preferred method to neuter my beloved dog?

The U.S. FDA study that approved Zeuterin™ found the product to be safe, effective and permanent. Think of the difference between a 28-gauge needle (the same size used to administer Botox to humans) and a surgical scalpel. The Zeutering procedure employs that small a needle and its use with proper protocol being followed resulted in nearly 99% of all dogs undergoing the procedure in the FDA study to need no medical intervention later. Zeutering is an option that should be explored by all pet parents considering having their male dog neutered.

Are you suggesting that castration not be used and that all dogs be Zeutered instead? If so, what makes Zeutering so much better than castration?

We are not discounting the effectiveness of castration. What we are suggesting is that all pet parents consider Zeutering as an option. Note that the FDA has approved it as safe, effective and permanent. The FDA process that leads to approval is rigorous and lengthy and to pass such scrutiny is not easy. In addition, by undergoing the Zeutering procedure, the dog's recovery time is substantially reduced, allowing pet and pet parent to be reunited more quickly. It is important that pet parents have their male dog(s) neutered to help reduce unwanted litters and euthanasia. Zeutering is one neutering option that deserves serious consideration.

What if, after my veterinarian does the research, he or she recommends against Zeutering?

Not all dogs are viable candidates for Zeutering. For example, dogs with undescended testicles, a disease or malfunction of the testicle, a history of allergic reaction to any of the components of the drug, pre-existing scrotal irritation or dermatitis, infected bite wounds, testicular cancers of any kind or transmissible venereal tumor, are not candidates for the procedure. If, however, your veterinarian is opposed to Zeutering because he or she is unfamiliar with the procedure and is making the recommendation based on lack of knowledge, please ask your vet to contact a Zeuterin™ representative via the "Contact Us" tab of the www.zeuterin.com website. We will reach out to your vet and provide information and support that will help educate him or her on the product and procedure.

Briefly, what are the pros and cons of Zeutering?

Zeutering is safe, effective and permanent, based on the FDA study that approved the Zeuterin™ product. The procedure requires less time, is less invasive than castration, and the recovery is typically much faster than traditional neutering. Based on veterinarian charges, the procedure can be 30-50% less expensive than castration. On the other hand, some dogs that are Zeutered experience pain, testicle swelling, vomiting, redness and, rarely, ulceration of the scrotal skin. During the FDA study, the adverse reaction rate that needed medical intervention was 1.1%. While that is a low rate, any adverse reaction, particularly when it is your dog, is unpleasant for both the pet and pet parent.

How old should my dog be when he is Zeutered?

Your dog is medically ready to be Zeutered when he is between 3-10 months old and testicular width in the 10-27mm range.

I have a senior dog. Will I put him at risk if I opt for Zeutering?

There are no known additional risks for senior dogs. The benefits for all dogs, particularly older dogs, include no need for anesthesia or risky surgical procedures, and it is a non-invasive procedure. Since the testicles remain intact - though they do shrink - your dog continues to produce a certain level of testosterone, which helps maintain the hormone function.

What does Zeutering entail? What is the procedure like and how long will it take?

Zeutering is done in three simple steps:

Sedation:

An injection is given to mildly sedate your pet to keep him still.

Injection:

The scrotal area is gently and thoroughly cleaned, and then a syringe containing Zeuterin™ is slowly injected into one testicle first, and then the other.

Tattoo:

The area is swabbed and then your pet is tattooed with a "Z" for 'Zeutered'. This indicates that he is neutered, although his testicles remain intact.

That's it! Your dog is sterilized and is ready to go home after a brief recovery. There is minimal pain or discomfort (if at all) through the entire procedure. You do not have to go through the trauma of having your pet surgically castrated, or undergo the pain and care of post-surgery. Protocol calls for you to check-in with your vet after 72 hours unless you observe something abnormal before that. Your vet will examine your pet for any adverse reactions and prescribe appropriate treatment, if needed. To see the Zeuterin™ procedure, click here.

Is my dog sterile immediately following the procedure, or does it take effect after a certain timeframe?

Zeutering effectively shuts down sperm production within one to three days of the procedure. However, sperm in the vas deferens and possibly the epididymis can reside for up to 30 days. It is recommended that a sexually mature Zeutered dog be kept away from a female in heat for up to 60 days post injection.

What happens physically to my dog's testicles?

During the procedure, a single injection of Zeuterin™ neutralized with arginine is administered directly into each testicle. Following the procedure, the testicles generally shrink and change texture due to fibrosis.

Will my dog look intact after the procedure?

Yes. Cosmetic testicular implants, like Neuticles, should not be needed or used.

How can an injection into the testicles be "virtually painless"?

What is unusual and not generally known about the physiology of the testes is that there are no pain sensors inside the testes, only pressure sensors. Zeuterin™-certified vets are specifically trained to deliver the injection very slowly to avoid triggering the pressure receptors. During the clinical trials, 97.5% of dogs (76% not even sedated) did not show signs of pain during the Zeutering procedure. Naturally, any needle inserted through the skin will cause pain for an instant. However, the needle used for this procedure is a very fine 28-gauge needle.

What does Zeuterin™ contain that can sterilize my dog and how does it impact testosterone levels?

Clinical studies have shown that testosterone production decreases 41-52% in treated dogs and the reduction is permanent.

What are the possible side effects?

Ark Sciences, the manufacturer of Zeuterin™, has administered more than 20,000 injections in order to sterilize dogs in the United States and in several Latin American countries. Our extensive follow-up and studies done by the FDA has shown only 1.1% of the dogs had adverse reactions that required medical treatment and 6.3% experienced minor reactions. Adverse reactions included:

  • Testicular swelling (normal reaction to injections)
  • Pain (dogs resisting sitting, or sitting with hind legs open)
  • Biting or licking the scrotum
  • Swelling of the prepuce
  • Irritation, dermatitis, ulceration, infection, dryness or bruising of the scrotum

Systemic reactions included:

  • Increase in white blood cell count
  • Vomiting
  • Loss of appetite
  • Lethargy
  • Diarrhea

Most reactions were seen within the first 7 days after the injection.

Do dogs experience pain following the procedure?

Over 93% of dogs did not show any signs of post-procedure pain.  When pain was detected, it was most commonly seen in the first two days. Our vets did not need to use any pain management medications in these studies. Vomiting was most commonly seen on the day of the injection (within one minute and four hours after the injection).

Have you done any studies on the long-term side effects of Zeutering?

Yes, we followed 40 dogs for over two years and have data on many of these dogs for over five years. Since 1999, when the initial clinical studies were performed, there have not been any reports of long-term side effects.

Is there anything I can do to help minimize adverse reactions for my pet pre- and post- procedure?

We recommend that you withhold food for 12 hours prior to the procedure to help prevent vomiting, which has occurred in 4% of dogs. Following the procedure, it is important that you closely monitor your dog's activity and that you take all precautions necessary to prevent injury to the testicles and to prevent your dog from licking or biting the scrotal area. Restrict your dog's exercise to leash walking, do not allow him to run, jump, or engage in play activity, or lay on hard or wet surfaces. Your dog's testicles may remain slightly enlarged, but non-painful, for a few months after the injection.

How is it different from traditional castration?

Historically, many chemicals have been used to sterilize male mammals, including dogs and cats. Some chemicals have actually dissolved the entire testis over time (chemical castration), making it equivalent to castration. Most of these methods cause suffering and serious reactions.

Will Zeutering affect my pet's behavior in any way?

As with surgical castration, Zeuterin™ may or may not eliminate male behavior, such as roaming, marking, aggression, or mounting.

Where do I take my pet if I decide to have him Zeutered?

We are currently training clinicians at spay/neuter shelters, animal centers and private practices on the product and procedure. However, only those clinicians are trained and certified will be able to perform or supervise the procedure. Vets who are interested in receiving the training are encouraged to visit the www.zeuterin.com website and use the "Contact Us" form so he or she can be contacted. In addition, dog owners and go to the same website and express interest in the procedure to get connected to certified Zeuterin™ practices.

Is Zeutering more expensive than traditional castration?

It depends on the location and quality of care being provided. The cost of product and other overall resources used in the procedure is 30-50% lower than traditional castration surgery.

What is Zeuterin™?

Zeuterin™ is a Zinc Gluconate with L-Arginine compound that sterilizes a dog with just one injection in each testicle. It is a safe, permanent, and virtually painless alternative to surgical castration.  Zeuterin™ is the new brand name for Neutrisol - the first non-surgical sterilant to receive regulatory approval from the U.S. FDA ).  The most important aspect of Zeutering a dog, apart from the product itself, is the procedure. Ark Sciences conducts extensive training programs for vets at clinics and dog shelters and only Ark Sciences certified shelters and vets can administer the injection.

end faq


Comming Soon .... 

Overview

Since our inception in 2007, we have been dedicated to the mission of improving the well-being and welfare of animals. This commitment is the driving force behind what we do today and will continue to play a primary role well into our future.

To that end, our world-class pharmaceutical products are specifically engineered to provide the least invasive, non-surgical sterilization processes possible. So, rather than castrating dogs, which can be painful and can lead to possibly harmful side-effects, veterinarians and animal welfare specialists now have a safe, reliable, and cost-effective sterilization treatment.

What’s more, Ark Sciences currently has patent protection on several key products that will revolutionize the treatment of animals. Our Research and Design team is at the forefront of nonsurgical sterilization. We are also closely affiliated with many universities worldwide, of which many are pioneers in the livestock pharmaceutical industry.

Click here to learn about Ark Sciences’ virtually pain-free, nonsurgical zinc neutering with Zeuterin™.

FAQ

Frequently Asked Questions

When is Zeuterin™ expected to be commercially available? It is now commercially available in the United States. Distribution is limited to Zeuterin™ certified licensed veterinarians. Dog owners can find a certifed by clicking here.

What is Ark Sciences doing to promote humane treatment of animals? Ark Sciences is a social entrepreneurship venture. It is a mission-based private company founded by Joe Tosini, an ordained minister to honor his commitment to making a difference in the world. He has chosen Ark Sciences and the vast potential of its technology, as the medium to achieve one of his missions: to alleviate the suffering of animals and humans.

The executive team at Ark Sciences will not rest until we dramatically reduce the US pet euthanasia rate of 4 million annually. Our vision is Full Adoption USA by 2020. We are now training veterinarians supplying them with Zeuterin. By February 2014, it is expected to be ready for sale at a price that will allow them to sterilize up to five dogs for the price of one castration (on average), five times faster, and five times safer. We have other products on the way that will be game changing for other animals.

Why is Ark Sciences targeting non-profits? A very small number of the 20 million intact male dogs in the US belong to breeders and dog professionals. Unfortunately with surgery, we are able to neuter only 20-25% of this potential to prevent unwanted litters. There are a lot of barriers that deter dog owners from surgical neutering today--anesthesia risk, cost, access, issue with mutilation/testis removal, long term health concerns, unpredictable behavior change concerns. etc. Animal welfare organizations have the mission and the experience in organizing outreach efforts to create awareness and increase neutering rates where it matters most. Many of them are signing up to become training centers for Zeuterin technology.

While organizations are free to choose their neutering methods, substituting one million neuterings via castration with non-invasive Zinc neutering among non-profits could save over $50M of donated dollars every year. Imagine the potential windfall of $50M becoming readily available for other animal welfare programs including dog adoption, responsible breeding, pet education, etc. The Ark Sciences executive team believes this to be an effective way to launch our mission and to educate the market on the best practice approach to neutering male dogs while addressing the problem of healthy, adoptable pets being euthanized.

What is Zinc Neutering? Zinc Gluconate (What is Zinc Gluconate? ) neutralized with L-Arginine (What is L-Arginine?) is the first compound ever to be approved by the FDA as safe for sterilization. It uses Zinc Gluconate (a trace element) and Arginine (an amino acid), both of which are essential for the body. In fact, they are health supplements that millions of us use every day. Sterile water is the only other ingredient, no preservatives are added.

A specific concentration of Zinc Gluconate neutralized with Arginine creates permanent sterilization with no adverse reactions needing medical treatment nearly 99% of the time (see the question on side effects below for other minor reactions). The mechanism is targeted and precise as established in the FDA study--Zeuterin caused sterility in 99.6% of young dogs 3-10 months old, while maintaining the endocrine function of the testes.

How is it different from Chemical Castration in the past? Historically, many hazardous chemicals (e.g., Calcium Chloride in Lidocaine or 90% alcohol, Chemcast) have been used on male mammal testicles, including dogs and cats. The objective is in this case is to actually dissolve the entire testis (chemical castration), making it equivalent to castration. None of these methods has ever been approved by the FDA as safe and effective and many have known to cause serious adverse reactions. None of these methods spare the endocrine function of the testicle like Zinc Neutering does to maintain the testosterone needed for metabolic activities.

How does Zeuterin™ sterilize a male dog? After the injection, the Zeuterin™ solution diffuses in all directions from the center of the testis. The specific concentration of Zinc (a targeted spermicide) used in our formula destroys spermatozoa in all stages of maturation in the seminiferous tubules and in the epididymis. The seminiferous tubules, which were replete with spermatozoa, are now emptied and collapse.

The dog's body increases blood flow and creates inflammation to heal. Within days, scar tissue (or fibrosis) from the healing process creates blockages in the seminiferous tubules, and more importantly, in the rete testis (the part of the testis that feeds the epididymis). All sperm must finally pass through these feeder tubules, which are now effectively closed as a result of the specific location of the injection. Zinc Gluconate and Arginine are absorbed and metabolized by the body. The male dog is now safely sterilized for life. View sample histopathology slides that were used to confirm permanent sterility here.

Since Leydig cells (cells responsible for the endocrine function of the testes) survive the procedure, the endocrine function of the testes remains intact. Over time, the seminiferous tubules, rete testis, epididymis, and prostate all atrophy--reducing the size and changing the texture of testicles.

What age should the dog be for the procedure? Zeuterin™ is currently US FDA approved for dogs 3-10 months old.

When does the dog become sterile? The sterilization procedure effectively shuts down sperm production within 1 to 3 days.  However, sperm in the vas deferens and possibly the epididymis can reside for up to 30 days.  Hence, a sexually mature zinc neutered dog must be kept away from female dogs in heat for up to 60 days post injection. Note that neutering via vasectomy and castration can leave sperm in the vas deferens remnants for up to 21 days.

Is Zeuterin™ safe? Yes, the FDA clinical trial for Zinc Gluconate established its safety and the FDA approval assures us all that Zeuterin™ is safe and effective.

The FDA Approval Study, several follow-up studies, and field trials all have established that Zinc Neutering can safely sterilize a dog and reduce its testosterone levels by about half using this non-invasive and virtually painless injection.

Are there any preservatives in your formulation? No. Zeuterin does not contain any preservatives. Simply discard any unused product 10 hours after first needle insertion into the vial to avoid complications due to possible product contamination.

What are the side effects? While adverse reactions requiring medical treatment occurred in 1.1% of the dogs, there were minor reactions observed in 6.3% of dogs during the FDA study. Local reactions included testicular swelling (normal reaction to the injection), pain (dogs may resist sitting or may sit with both hind legs open), biting and licking at the scrotum, swelling of the prepuce and irritation, dermatitis, ulceration, infection, dryness or bruising of the scrotum. Systemic reactions included an increase in the white blood cell count, vomiting, anorexia (loss of appetite), lethargy (tiredness or abnormal attitude), and diarrhea.

Most reactions were seen within the first 7 days after the injection. Over 93% of dogs did not show any signs of post procedure pain. When pain was detected, it was most commonly seen in the first 2 days. No pain management medications were used in the study. Vomiting was most commonly seen on the day of the injection (within 1 minute and 4 hours after the injection). It is recommended to withhold food for 12 hours prior to injection to help prevent vomiting, which occurred in 4% of dogs. Your dog's testicles may remain slightly enlarged but non-painful for a few months after the injection. Proper injection technique and owner observation post-injection is critical to avoid any potential undesirable side effects.

Are there any studies on long-term side effects? Yes, 40 dogs were studied for over two years (fourteen in human years) and a few of the dogs were informally checked to be fine after 5 years.  Since 1999, when the initial clinical studies were performed, there have not been any reports of long-term side effects related to the procedure.

Does this sterilization procedure increase or decrease the risk for testicular or prostate cancer? Long-term observations have shown no increase in risk for testicular cancer. However, no studies have been performed to evaluate if Zeuterin™ decreases the risk of testicular cancer. For prostate cancer, see A population study of neutering status as a risk factor for canine prostate cancer that concludes that surgically castrated dogs are at double the risk to get prostate cancer. To the extent such increased risks are related to testosterone elimination caused by castration, higher risk of such cancers is not expected after zinc neutering.

What happens physically to the testicles? During the procedure, a single injection of Zeuterin™ is administered directly into each testicle. Following the procedure, over time, the testicles generally shrink and change texture due to fibrosis. Long term changes in testicle size may be asymmetrical.

Will the dog look intact after the procedure? Yes. Cosmetic testicular implants like Neuticles should not be needed or used.

How can an injection into the testicles be "virtually painless"? Pain is either somatic or visceral. Any needle inserted through the skin will cause somatic pain for an instant. However, the needle used for this procedure is a very fine 30 guage Botox needle that people over forty may even find hard to see, minimizing that pain.

What is unusual and not generally known about the physiology of the testes is that the severe testicular pain experienced is visceral and triggered by rapid pressure deforming the testicular capsule. Ark-certified vets are specifically trained to deliver the injection very slowly to avoid triggering the testicular pressure receptors. Indeed, 97.5% of dogs (76% not even sedated) in the FDA study did not show any signs of pain during the procedure.

How does zinc neutering affect testosterone levels? Studies have shown that testosterone production decreases 41-52% in treated dogs. The reduction is permanent.

How is testosterone lowered by Zeuterin™? 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.

Does this procedure have any effect on behavior? As with surgical castration, Zeuterin™ may or may not eliminate male behavior such as roaming, marking, aggression, or mounting in dogs. Formal statistical evidence comparing neutering via zinc versus castration is not there.

Some studies, not yet peer-reviewed, suggest a correlation between several undesirable behaviors in dogs that have been neutered via castration (See Behavioral and Physical Effects of Spaying and Neutering Domestic Dogs (Canis familiaris) by Parvene Farhoody in May, 2010). To the extent such undesirable behaviors seen in surgically castrated dogs are caused by the complete elimination of testosterone, Zinc Neutering would be unlikely to cause them.

Any known benefits/risks for senior dogs? Benefits: Avoid anesthesia/surgical procedure and maintain hormone function. Risks: No known additional risks

Are there any case studies on your products? Yes. Here is a compilation of some reports that have been published (NEUTERSOL: A CLINICAL PERSPECTIVE, James R. Weedon, DVM, MPH, DACVPM, Spay-Neuter Assistance Program, Inc., Houston, TX)

Why do adverse reactions (beyond side effects) occur in 1.1% of treated dogs? There are some misconceptions about this procedure being "dangerous" and that Zinc Gluconate and Arginine create some acid-like deadly combination. The truth is that this combination has the same pH as water (i.e. 7), will not irritate normal skin, and 98.9% of dogs did not need any medical attention after the procedure during the FDA study.

The adverse reactions have several causes:

  1. Undetected scrotal dermatitis during the screening exam (sometimes hidden by thick scrotal fur because it is not shaved) combined with even a small product spill during the injection.
  2. Fast injection speed leading to testis contraction, creating product spill into the scrotum.
  3. Improper site entry or needle size leading to product diffusion outside the testis.
  4. Incorrect dosage determination leading to product diffusion outside the testis.
  5. Improper disinfection of the scrotal area or needle contamination leading to introduction of harmful bacteria into the testicle.
  6. Testicular abnormalities or a rare allergic reaction to ingredients may also be possible causes.
  7. Other diseases and disorders that compromise the dog's ability to tolerate the procedure.

Some of these issues can cause an itch or irritation in the testicle or scrotum causing the dog to lick and bite as there is no E-collar in place after sterilization. If the dog is not monitored to prevent the licking and biting, serious irritation, infections, and/or ulcers can result. Most of these conditions can be treated with topical ointments. In some instances, scrotal ablation or castration may become necessary.

In free roaming or poorly maintained dogs (depending on the shelter), scrotal dermatitis is more common, and after care may not be possible; rate of adverse reactions and severity is documented to be higher in these populations. In such instances, dogs that are not surgery candidates may well be rejected for zinc neutering as well. In disease-prone areas, proper disinfection and follow-up protocols must be meticulously followed.

As new organizations embark on zinc neutering, they should expect to treat one scrotal ulceration for every 100 dogs sterilized via scrotal ablation and possible castration. Most scrotal irritations observed during the first 3 days heal on their own unless the dog starts to lick and/or bite the area and creates an infection.

Experience shows that there may be a learning curve for vets in handling these adverse reactions effectively. A hotline will be established for support and record keeping. Over time, these rates should reduce to 1-2 dogs needing any medical attention for every 200, which is the rate observed in controlled studies in the US environment (rates observed in rural Mexico were much higher due to the condition of the dogs). Such costs should be factored in to determine overall savings for the non-profit organization.

How do I minimize adverse reactions? To minimize the occurrence of adverse reactions, such as scrotal irritation, inflammation or infection, it is critical that you closely monitor your dog's activity post-injection and that you take all precautions necessary to prevent injury to the testicles and to prevent your dog from licking or biting the scrotal area. Restrict your dog's exercise to leash walking; do not allow your dog to run, jump, or engage in play activity; do not allow your dog to lay on hard or wet surfaces; do not allow your dog to lick or bite the scrotal area.

When to choose non-surgical zinc neutering over castration?
Barring few exceptions, we should be sterilizing all our pets to end the needless suffering and euthanasia due to the overpopulation of our dearest companions. A non-invasive procedure like Zinc Neutering should always be the first procedure considered. One is advised to understand the pros and cons of surgical neutering to make an informed decision (See Advantages and Disadvantages of surgical neutering on Wikipedia )

For dog breeds more susceptible to complications from anesthesia (e.g., brachycephalic breeds like Pugs, Pekingese, Bulldog, etc.) or for dogs compromised in any way and at higher risk of anesthesia death, Zinc Neutering may well be the only humane option. (See The risk of death: the Confidential Enquiry into Perioperative Small Animal Fatalities in which one hundred and seventeen centres participated in the study between June 2002 and June 2004. During that time, 98,036 dogs, 79,178 cats and 8,209 rabbits were anesthetized or sedated and 163, 189 and 114 anesthetic-related deaths were identified respectively, resulting in risks of death of 0.17% in dogs, 0.24% in cats and 1.39% in rabbits).

In the hands of an experienced practitioner, a non-invasive zinc neutering injection is faster, gentler, safer, and cheaper than castration. Zeuterin™ will sterilize the dog and eliminate testosterone needed to support spermatogenesis, while preserving testosterone needed for other metabolic functions, a roughly 41-52% permanent reduction. While retaining some testosterone has beneficial effects, this procedure may not reduce the risks of diseases associated with male hormones, such as testicular (tumor rates are 7% but rate of metastatic testicular cancer is less than 1% overall) or perianal tumors (uncommon, as only 2% of all skin tumors are peri-anal but rate of metastasis is over 50%) in dogs.

Studies show that for many dog breeds and individual dogs with genetic predispositions, surgical castration may compromise long-term health. (See Long-Term Health Risks and Benefits Associated with Spay / Neuter in Dogs Laura J. Sanborn, M.S., May 14, 2007) If such long-term risks related to surgical castration are due to near elimination of testosterone in the body, they are unlikely to manifest after zinc neutering.

It is widely accepted that neutering suppresses mating behaviors to varying degrees and also that there are no guarantees. However, there is emerging evidence that surgical castration may negatively impact dog behavior that is not mating related (e.g., fear, anxiety, trainability, etc.). To the extent such undesirable behaviors are the result of testosterone elimination, zinc neutering is unlikely to manifest them.

Side-By-Side Comparison of Surgical Castration and Zinc Neutering

Is Zeuterin™ more expensive than surgical castration?
It should not be. Based on the Ark's potential offer to non-profits in the US, the cost of non-surgical sterilization will be 1/5th the cost of castration (on average). However, the real value of zinc neutering may become apparent when one considers the dog’s safety (1 in 601 dogs die from anesthesia complications), long-term health, and behavior.

What is the connection between Neutersol™ and Esterilsol™?
Neutersol and Esterilsol™ use the same mineral compound (Zinc Gluconate neutralized by Arginine) Neutersol was approved by the US FDA as safe and effective for use in 3-10 month dog sterilizations. Neutersol was distributed by Addison Labs starting in 2003 for about three years. Ark Sciences has acquired all rights to the Neutersol technology.

Esterilsol is Ark Sciences' product for international markets. Esterilsol™ is now registered in four countries and pending approval in key markets around the world. It is approved for all dogs over 3 months of age in Mexico. Over the last four years, Ark Sciences has utilized Esterilsol™ extensively in Mexico in dogs three months and older to assess its efficacy as well as refining and improving the injection technique to minimize reactions.

In early 2011, Ark Sciences, having acquired full rights to the intellectual property for Neutersol, started to set up a US manufacturing site. This manufacturing facility is expected to start supplying commercial product by February 2014. Initial focus will be on non-profit animal shelters and high volume spay/neuter clinics at a game-changing low price.

Why did you not win the Found Animals Michelson Prize of $25M for your technology?
The Michelson Prize is to license a technology that works on male and female dogs and cats. Our technology is only for male dogs and cats and not available for licensing.

Why did you develop a product only for males?
Dr. Wang, the co-inventor, wanted to come up with a solution that did not create system-wide reactions or imbalance. This objective eliminated most approaches that can usually be applied to both males and females. The localized effect of Zinc targeted at sperm cells, and sperm cells alone, makes it a safe and permanent sterilant.

How do I get my dog sterilized with Zeuterin™?
Most animal centers or shelters will have trained vets doing sterilizations starting mid- 2014. For privately owned dogs, you can request Ark Sciences to send an offer to your dog's vet to get certified. You can do this by getting on the Ark waiting list. This link will also connect you to a local certified vet, if available.

Is there any way to verify that the procedure has been done correctly? Efficacy rate at the FDA trial was documented at 99.6% (about the same as a perfectly taken pill) so the dog is considered neutered after the procedure and a sterilization certificate is provided. If desired, sterilization of the dog can be verified by viewing the dog semen under a microscope after 30 days.

How do you identify a treated dog? Leading microchip companies are capable of keeping neutering status in their databases. Tattooed serial numbers can also be used if a microchip is not practical. This will prevent the dog from being castrated if rescued at a later date.

During the "training period", we will use an optional "Z" tattoo next to the inner thigh area. It will be formed using a tattoo pen. Since this would be the most invasive part of the whole sterilization procedure, we will have to analyze the results to see if this method will survive as a standard practice. Veterinarians familiar with the sterilization procedure will also be able to tell if a dog has been sterilized after a few months by palpating the testicles--the testicles become smaller and firmer as scar tissue forms over time.

Many dog owners are understandably concerned about onlookers and "dog run" friends giving them the evil eye--assuming their anatomically correct male dog is intact. To address this concern, we are finishing up final designs on collar add-ons and fun T-shirts for dogs neutered via zinc rather than castration to flaunt their special status.

Can veterinarians sign sterilization certificates for treated dogs? Yes. Sample certificates are available on This email address is being protected from spambots. You need JavaScript enabled to view it. .

I’m a vet. How do I learn to use your product?
This product is only available to licensed veterinarians who are trained in the Zeuterin injection technique. You can sign up for an online training seminar with 2 CE credits right away. After an in-person wet lab, certification is complete. Please contact us if you are interested in getting more information about the training or the procedure.

Do you have to be a licensed veterinarian to neuter using your product? More than that, it must be administered by a veterinarian or a vet tech under the supervision of a licensed veterinarian. Further, each vet or vet tech must be fully trained by Ark Sciences prior to administering Zeuterin™.

Why do you have such a strict training and data collection protocol? Is the procedure prone to errors? No. Once the vet is trained, errors are uncommon. Adverse reaction rates in the FDA study and in field trials are substantially lower than castration even without a tight training protocol. It became clear from our FDA study and other field experiences that even the low 1.1% adverse reaction rate (ones that required medical treatment) could be reduced if the injection technique is well understood and followed. Improvements from 90% to 99% are much easier than going beyond 99%--hence our intense focus on the procedure and data collection to get real-time feedback. Our goal is to create a near perfect track record of our procedure as each and every dog is important to us.

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