Sterilization implant launch in US eyed; research on gene-based approach advances
Photo courtesy of Alli Berry
Flynn, a 14-month-old border collie, received an implant between his shoulder blades six weeks ago that renders him infertile for about a year.
Flynn's behavior seemingly made him a perfect candidate for castration. As soon as the rambunctious border collie hit adolescence, he began scuffling with other dogs and reacting to cars, bikes and joggers. His owner, Alli Berry, needed a way to calm him. But a past experience caused her to question whether surgery was the answer.
"I've had an aggressive dog before that I just castrated because that was what you were told to do," Berry said. "That didn't help at all, and in fact made him a bit worse."
Berry, whose disobedient canines inspired her to set up a dog-training business in Melbourne, Australia, soon heard about another option: implants that cause temporary infertility. The drug-based treatment, marketed under the brand Suprelorin, is injected under the skin and renders a male animal infertile for up to 12 months, no surgery required.
Berry figured trying the chemical route on Flynn would enable her to test-drive infertility before deciding whether to commit to surgery.
She is among a small but growing minority of pet owners who are opting for nonsurgical techniques that offer temporary sterilization, as awareness of their availability increases among veterinarians and the general public.
Separately, research funded by the Michelson Found Animals Foundation, a nonprofit group based in Los Angeles, is progressing on a gene-based therapy that would offer permanent nonsurgical neutering, initially for females and then potentially for males. Its debut, however, is several years away.
Surgical sterilization very much remains standard practice in the veterinary community and is encouraged in many jurisdictions as a means of preventing pet overpopulation and mass euthanizing. Lifelong sterilization can provide health benefits to animals, such as a reduced risk of mammary and reproductive-organ cancers. Owners may benefit from less pet aggression, urine marking and unwanted sexual behavior.
Still, some pet owners are requesting more choice as research indicates that desexing, particularly for prepubertal animals of certain breeds, might pose health risks, too, such as joint disorders, obesity, cancer and urinary incontinence. Several other studies show that castration, long understood to curb male aggression, might have the opposite effect on some animals, though research on the subject has produced conflicting results.
Flynn, now 14 months old, received his sterilization implant on Feb. 7 for AUD$250 (US$187), including the veterinary fee. Berry has been patiently waiting out the six weeks it takes for the implant to take effect and is keeping a blog of his progress on Facebook.
Initially, she saw signs of a brief spike in testosterone the implant causes before the fall. "There was a lot of overt sexual behavior," Berry said. "You said hello to him and he kind of air-humped."
In recent days, Flynn's behavior has improved. "It's definitely kicked in because he has very much mellowed out," Berry said on Monday. "He's not perfect, but he's on his way there."
The checkered history of chemical neutering
Nonsurgical desexing techniques have been available for many years, though their use has been patchy. Zinc gluconate, which is injected directly into the testicles and causes permanent infertility, was unsuccessfully marketed twice: From 2003 to 2005, branded as Neutersol, and from 2014 to 2016, branded as Zeuterin. Various explanations have been offered for the brands' demise, including the idea that piercing testes with a needle can induce squeamishness, including among veterinarians.
Progestins such as megestrol acetate, which are synthetic forms of the hormone progesterone and are administered to female dogs and cats, also have been around for years. They offer short-term suppression of fertility. Injections last up to six months. Oral medications are administered weekly.
Potential side effects, such as uterine infections, diabetes and Cushing's disease, have sullied progestins' reputation internationally. Still, use of oral megestrol acetate may have increased during the Covid-19 pandemic, as lockdowns made it harder for pet owners to access routine surgery, said Dr. Joyce Briggs, president of the Alliance for Contraception in Cats & Dogs (ACC&D), a nonprofit group based in Portland, Oregon, that advocates nonsurgical desexing.
Cats, in particular, were targeted for treatment because they tend to reproduce more rapidly than dogs. "Megestrol acetate was revisited as kind of a Band-Aid for female cats to keep them out of heat for up to 30 weeks while people were waiting for spay appointments," Briggs said. On its website, the ACC&D suggests megestrol acetate's poor reputation is perhaps undeserved, citing research that shows it's relatively safe when used correctly.
Implants that offer temporary sterlization in males appear to be generating more buzz because their side effects so far have been shown to be minimal. Suprelorin, the only such product available on the market, is sold in 38 countries, including in Australia since 2007 and in Europe since 2008. It recently was launched in China, Mexico and Uruguay, and its French owner, Virbac, is eyeing potential launches in the U.S. and Canada. (Suprelorin is available in the U.S. currently but allowed for use only in ferrets.)
Some veterinarians in North America appear to be curious about it: On message boards of the Veterinary Information Network, an online community for the profession and parent of the VIN News Service, several practitioners have raised queries about the product's efficacy and availability.
The implant's active ingredient, deslorelin, acts like gonadotropin-releasing hormone (GnRH), which controls the secretion of other hormones involved in fertility. The implant, placed under the skin between an animal's shoulder blades, slowly releases deslorelin, desensitizing the pituitary to GnRH's effects and blocking testicular function.
Virbac is "seriously considering" introducing Suprelorin for use in dogs in North America, most likely starting with Canada, Dr. Christelle Speiser, a marketing and medical manager for Virbac, told VIN News. She said the company is in discussions with the U.S. Food and Drug Administration about possible approval for dogs in the U.S., as well.
"In the U.S., there is for sure a very strong tendency to surgically neuter pets," Spieser said. "At the same time, we are receiving a lot of queries from vets in the U.S., but also from pet owners, about Suprelorin implants. This is encouraging."
The product also is effective in cats, though, like for dogs, approval for use in the species varies by jurisdiction. Apart from offering a reversible alternative, pet owners may be attracted to nonsurgical sterlization because it avoids the immediate stress, pain and health risks associated with surgery, including from the use of anesthesia, according to the ACC&D.
Changing perceptions among a small subset of veterinarians, animal welfare advocates and others about the need for reproduction control, stoked by a shortage of dogs in some U.S. states during the pandemic, also could encourage demand for nonsurgical solutions. Reversible products such as Suprelorin, Briggs suggests, could enable clients to let their dogs sire puppies later in life. "I think it's important that we have better ways of deciding how to deploy sterilization to make sure we're creating the right number of dogs — and that those dogs are going to be successful in families," she said.
To be sure, sterlization implants for males still appear to account for but a small fraction of neutering procedures, even in the countries where they have been around the longest.
Cultural preferences, cost barriers influence demand
Alli and Flynn
Photo courtesy of Alli Berry
Alli Berry, a dog trainer based in Melbourne, Australia, is Flynn's owner. She has been keeping a blog on Flynn's progress with his infertility implant, which takes six weeks to fully kick in.
Dr. Paul Hansen, a veterinarian who practices in the Sydney suburb of Woollahra, has been prescribing the implant for 10 years. He finds some clients include it in their annual pet health checks — getting it injected alongside vaccinations and routine blood screening, for instance.
For many, the appeal is to give desexing a trial run to ensure surgery won't adversely affect a pet's personality. If the dog is still chipper after one or two years, most clients opt for surgical neutering, Hansen said. "I've only got two dogs that have had Suprelorin injections every year for their entire lives."
Hansen is aware of the latest research on potential health risks associated with desexing. But like many veterinarians in Australia, he urges his clients to have their pets surgically spayed or castrated after considering potential benefits to the animal, pet owner and community at large. "The only discussion that I tend to have is about the idea of delaying desexing of large-breed dogs until they are at a mature body weight with fully developed ligaments and bones," he said.
Moreover, pet owners in countries such as Australia, the U.S. and the United Kingdom, are encouraged by law to have their animals neutered surgically. In Hansen's state of New South Wales (NSW), for instance, neutering isn't compulsory but is encouraged by more expensive licensing requirements for intact animals. Pet owners who opt to leave their dogs intact also may be more vulnerable to legal consequences if their pet is involved in an altercation. Nonsurgical neutering is not counted as castration under NSW law because it is not permanent.
Overall, Hansen said Suprelorin accounts for about 1% to 2% of the desexing procedures performed at his practice. He doesn't stock the product and orders it only on demand. "It's very much a niche kind of option," he said.
Still, Berry's experiences indicate that increased awareness might spur more interest in the product. When she wanted Suprelorin for Flynn, having heard about it in dog-training circles, she was surprised how it hard it was to find. "I called my clinic and they had no idea what I was talking about," she said. "One vet got back to me and suggested that I look into a clinic that specialized in reproduction.”
The extent to which demand is changing is difficult to measure definitively, in part because Virbac, like many pharmaceutical companies, doesn't regularly disclose sales figures for individual products. In a market filing last year, though, it said Suprelorin revenue for the six months through June 2021 had risen 29% year-on-year, without providing a base comparison figure or detailing what proportion of that growth came from geographic expansion. Dr. Michelle Murdoch, a product manager for Virbac in Australia, told VIN News that between 2019 and 2021, the company had seen a 40% rise in Suprelorin implant sales Down Under.
Places where surgical desexing is less popular, such as Europe and South America, may be more receptive to adopting nonsurgical neutering practices. For instance, in many northern and central European countries, such as Germany, Norway and Sweden, surgical desexing is widely considered to be a form of animal mutilation. Surgical neutering also is less common in some southern European countries such as Italy, Spain and Greece, due to cultural preferences, often influenced by religious beliefs, to leave animals as nature created them.
Castration especially may be seen as emasculating in more conservative cultures, though an element of solidarity between human males and their canine counterparts can be evident worldwide. Such concerns, at least in an aesthetic sense, have fueled the development in the U.S. of "Neuticals," plastic implants placed in the scrotum of a castrated dog so he can retain a natural look.
Dr. Stefano Romagnoli, a reproduction specialist based in Padua, Italy, sees promise in nonsurgical neutering products such as implants that contain deslorelin. "We have been among the first countries to use them and now quite a lot of veterinarians are using them in Italy," he told VIN News. "These often are veterinarians who are specialists in reproduction — the majority of GPs [general practitioners] need to get more information and experience to become confident enough to use them, but they're gradually spreading."
Romagnoli, who has participated in several studies on nonsurgical desexing, is head of the World Small Animal Veterinary Association's Reproduction Control Committee. The committee is finalizing a survey destined for thousands of veterinarians globally that will help it build a database on how spaying and neutering is performed, and formulate guidelines on reproductive issues.
Separately, Romagnoli is involved in research looking at the long-term use of the implants. Their cost, he said, even for short-term use, could act as a brake on growth. "It's not something that could be done easily on a large number of animals for a lifetime," Romagnoli said. "But with increased use, the price might drop."
Suprelorin implants cost around €80 (US$88) each, Virbac's Speiser said, with the expense to pet owners varying considerably, depending on markup, consultation and injection costs charged by veterinarians. Hansen, the practitioner in Sydney, said the price for using one annual implant costs roughly half as much as one permanent desexing surgery. "For a lot of people, it's cost prohibitive," he said.
Virbac's Spieser said there are limits to how far the price can be reduced because Suprelorin isn't especially easy to manufacture. "Even though we are very conscious of the limitations that could be related to the price, we have to be realistic," she said.
Developing a cheap, permanent nonsurgical solution
The ACC&D's Briggs is hopeful that nonsurgical neutering could help address stray pet problems in low-income countries where access to veterinary surgery is limited. A low-cost solution that offers permanent infertility may be needed for nonsurgical neutering to become mainstream, she maintains, since not everyone can afford to seek treatment on multiple occasions, if at all.
"I have committed my career since 2008 to this field because I think nonsurgical neutering can be a game-changer," Briggs said. "And I hope we can achieve that, rather than making incremental change."
Enter the Michelson Found Animals Foundation, which is funding the development of permanent nonsurgical spaying and neutering solutions based on gene-transfer technology.
The researchers already have established proof-of-concept for a lead candidate for females, according to Thomas Conlon, the foundation's chief scientific officer. "We've come very far with one of our technologies and we're extremely excited about it," he said in an interview.
Still, it could take another six or seven years for the treatment to become commercially available, owing, in part, for a need to meet regulatory requirements, including by conducting clinical trials, Conlon said.
Gene-transfer technology involves placing a gene into a vector, such as a virus or nanoparticle, and injecting it into the patient to cause a desired effect, such as the suppression of fertility. Such technology already has been used to treat or prevent several diseases, including spinal muscular atrophy and cancers such as melanoma and B-cell lymphoma.
Conlon said the treatment intentionally is being designed as an intramuscular injection for ease of use, either in the field or at veterinary clinics. Demand for the product could come from pet owners averse to surgical neutering, or from governments and charities attempting to reduce populations of stray animals. The lead candidate is female-focused, Conlon explained, because sterilizing females has a greater impact on population control than sterilizing males.
He added that an important aim is to make the treatment affordable. "Ultimately, our goal is to have a product that's within the cost range of traditional spay and neuter," he said.
Even if the foundation succeeds, there will remain a market for approaches that provide temporary sterilization. Just ask Berry, who said she'll likely have Flynn surgically castrated in a month or two, should the recent improvement in his behavior persist. "Whether he'd gotten better or not, it was good to have the opportunity to actually see what it was going to do to him first," she said.