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12/12/12

Alternatives to neutering your male dog


Owners who do not elect to get their dogs desexed often request other ways of preventing or managing the breeding, behavioural or medical problems faced by their entire pets. Which preventative measures and treatment options can be offered really depends on what the owner is trying to achieve. Owners just looking to prevent their dog or dogs from breeding can make use of a range of birth/pregnancy control measures available (sections 10a-10f). Owners looking to control or manage testosterone-mediated behavioural or medical problems (e.g. prostate hyperplasia, perianal adenomas) can look at option 10g. The reality is, however, that no one of these alternative measures alone will manage all of the problems of overpopulation, behaviour and testosterone-mediated health issues like desexing will. Additionally, many of these alternative solutions do come with significant side effects and health risks of their own. Desexing is always the best choice.

IMPORTANT: Check your local state and regional laws before opting for any of these alternatives. Animal population control laws are changing and increasing all the time. It may be illegal for you to keep a non-breeding-purposes (i.e. an entire male "stud" dog not owned by a registered breeder) entire male dog on your property. 


Canine birth control method 1 - physically separate the dog from the bitch and prevent roaming.


If your main concern is preventing your entire male dog from impregnating one or more of your entire females or other people's dogs in the neighbourhood, you can devise ways of preventing the dog from physically accessing your females and leaving your property.

This is a scenario that commercial dog breeders have to deal with all the time: they can't get their stud male desexed, but do not want him to breed ad libitum with everyone. In these situations what breeders tend to do, and what you can do too, is house their dogs (males and females) individually in specially-constructed, escape-proof dog runs so that male dog escape and mismating can not occur. 

Simply constructing a separate fenced-off yard is not enough! It needs to be escape proof and that includes putting a roof on it. Many dogs will scale massive heights and climb high fences to reach a female in heat. 

Simply keeping the dog away from the bitch while she is in heat (in season) is also no guarantee of her not falling pregnant. Most owners can not determine accurately when a dog's heat starts and ends (it can be a month long in all!). Moreover, this technique will not stop your dog from escaping its yard and wandering off to find other neighbourhood females to mate with. 

Not desexing the male animal in this situation, however, will do nothing for his behaviour or health. He will still be inclined towards showing unfavourable entire-male behaviours (roaming, aggression, dominance, territory marking etc.) and he will still be prone to a range of testosterone-mediated health problems. 

The best option is to get the male and female animals in your household desexed if they are not breeding animals. There are important behavioural, medical and population-control benefits to be gained by having each of the sexes desexed.

 Canine birth control method 2 - spey (spay) your bitch.


It never ceases to amuse and amaze me how many owners (particularly male owners) are horrified by the thought of having their male animals desexed and yet will happily get their female animals desexed, even though female dog desexing is a far more invasive and risky procedure to perform than male dog neutering is. It possibly harks back some underlying cultural belief that pregnancy is the woman's problem.

It is however, an option. If you do not want your male animal to impregnate the female animals in your household, you can elect to have the females desexed so that the male has nothing to mate with. Certainly, there are important health benefits to the female animal if she is desexed and desexing her will prevent dogs outside your household from coming over and getting her pregnant. 

Not desexing the male animal in this situation, however, will do nothing for his behaviour or health. He will still be inclined towards showing unfavourable entire-male behaviours (roaming, aggression, dominance, territory marking etc.) and he will still be prone to a range of testosterone-mediated health problems. 

The best option is to get the male and female animals in your household desexed if they are not breeding animals. There are important behavioural, medical and population-control benefits to be gained by having each of the sexes desexed. 

Canine birth control method 3 - "the pill" and female oestrous (heat) suppression.


There are a number of ways to suppress oestrus (heat, season) in female dogs and therefore prevent them from becoming pregnant by an entire male animal. Most of these solutions involve manipulating the female animal's reproductive cycle (estrous) cycle using a range of reproductive hormone and reproductive-hormone-like chemicals. Some of these include: progesterones (progestagens) and progesterone-like chemicals and testosterone and testosterone-like anabolic drugs. 

The problem with many of these hormonal estrous suppression solutions is that they can have potentially devastating, life-threatening and/or aesthetically displeasing side effects. 

Progesterones:

The progesterone and progesterone-derived drugs commonly used to temporarily or, with repeated use, permanently suppress estrous in the bitch include: medroxyprogesterone acetate (MPA), megestrol acetate and proligestone. Having less or fewer side effects than the testosterone-based products, progesterones are the most common drugs used for estrous suppression in the bitch. They are not, however, without certain important potential side effects.

Common side effects of progesterone use in the bitch include: lethargy (sleepiness); increased appetite; weight gain and, occasionally, loss of hair or change in hair colour and shrinkage of the subcutaneous tissues at the site of injection. Insulin resistance and diabetes mellitus may also be induced by long-term progesterone usage as can growth hormone problems like acromegaly. Progesterones can sometimes mimic the effect of corticosteroids in the dog, resulting in a Hyperadrenocorticism effect (Cushing's disease) and a liver condition called steroid hepatopathy (a liver full of fat). 

Some bitches treated with progesterone products have been found to develop severe mammary enlargement, mammary nodules and even nasty mammary tumors (breast cancer). 

In breeding animals, the use of certain oestrous-suppressing progesterone drugs has been found to result in reduced fertility for many individuals, thereby reducing the affected animals' value as breeding animals. Permanent infertility can be induced if the animal receives long term, prolonged progesterone treatments or is given progesterone prior to its first cycle (never give progesterones before the first season).

The incidence of false pregnancy (also called pseudopregnancy or phantom pregnancy) may also be increased by the use of progesterones. 

Animals treated with progesterone whilst already pregnant may have delayed parturition, resulting from a failure of normal hormonal birth-induction processes (i.e. the bitch does not receive the 'signal' telling her body when to give birth). This delayed parturition results in the death and mummification of the fetuses inside the womb. These animals will often need a caesarean section to give birth. The milk production of such animals (ones given progesterone while pregnant) will also be adversely affected by the progesterone usage (the animal's milk production is inhibited by progesterone) and the live pups born by C-section may require milk supplementation and hand-rearing. 

More catastrophically, the use of certain heat suppressant progesterone drugs (e.g. medroxyprogesterone acetate, repeated doses of megestrol acetate) has been shown to increase the risk of the bitch developing pyometron - a severe, life-threatening, infection and abscessation of the animal's uterus. Many bitches that develop pyometron need to be desexed to save their lives and those that are treated medically may not be able to go on to produce viable litters due to permanent uterine damage and scarring. The risk of pyometron does not seem to be as high with proligestone as it does with some of the other progestagens. 

Author's note: of all of the progesterone products marketed for this purpose, proligestone (proligesterone) is considered to be one of the safer ones, with the lowest incidence of side effects. It is traded as Covinan. Megestrol acetate has more side effects, but these are not too common provided the drug is used according to instructions and not for prolonged periods of time. The use of medroxyprogesterone acetate (MPA) is not recommended at all for this purpose because it stays in the body for many months and has a high incidence of severe reproductive and mammary side effects. 

Testosterones:
The use of testosterone and testosterone-like products to reduce cycling in the bitch is rarely done these days, the side effects often being deemed more unacceptable than those of the progesterone-type products. 

Testosterones can make the female animal look and act more masculine (e.g. it may show increased muscle development and clitoral enlargement) and cause it to develop many of the same behavioural issues as the entire male animal (e.g. mounting and aggression). Testosterone-treated females are also more prone to developing many of the same testosterone-induced medical conditions - e.g. perianal adenomas - more commonly encountered in male dogs. 

Testosterone-treated animals are more prone to developing liver problems (some develop jaundice) and renal disease. They are more prone to developing oily, stinky-smelling skin and various skin conditions. They sometimes develop vaginitis and vaginal discharges. Treated animals are also more likely to develop fertility problems (subfertility issues) later on.

Author's note - because testosterone-based products used in pets are similar to those used illegally in human body-building competitions and competitive sports, they are becoming more and more restricted for veterinary use because of the risk of them falling into the wrong hands. This is another reason why progesterone has overtaken testosterone for pet estrous suppression. 

Because of the risk of severe, life-threatening side effects, hormonally-induced heat suppression should only be used as a very last resort and, even then, only in animals that are intended to be used as breeding animals later on (breeders need to be aware that significant loss of fertility can occur with their use as well as uterine diseases like pyometron and mammary diseases like breast cancer). It is far safer to isolate your breeding bitch from the males when it is in heat (season) than it is to try to artificially manipulate the female animal's reproductive cycle and keep heat suppressed. If breeding is not an aim for you, it is far better and safer to desex the female dog than it is to try to manipulate its reproductive cycle using hormones.

Remember again that not desexing the male animal in this situation will do nothing for his behaviour or health. He will still be inclined towards showing unfavourable entire-male behaviours (roaming, aggression, dominance, territory marking etc.) and he will still be prone to a range of testosterone-mediated health problems. 

The best option is to get the male and female animals in your household desexed if they are not breeding animals. There are important behavioural, medical and population-control benefits to be gained by having each of the sexes desexed.

Canine birth control method 4 - the "male pill" - fertility suppressing implants (contraceptives) for male dogs.


The GnRH analogues are a group of drugs that produce a negative effect on testosterone production by exerting a negative feedback effect on the brain-derived hormone (called luteinising hormone or LH) that is responsible for stimulating the testicles to produce and release testosterone. By preventing the production of LH, the GnRH analogues essentially prevent the LH-mediated production of testosterone by the testicles. 

The GnRH analogue most commonly used in Australia is deslorelin (tradenames include Suprelorin-12). It is currently being marketed as a male form of "the pill". It is a slow-release, 12-monthly, contraceptive implant that suppresses male testosterone production to such a low level that canine fertility, sperm production, ejaculation and libido are all but non-existent. The male animal essentially becomes infertile whilst it has the implant and is unable to father any pups. 

Because of this product's inhibitory effects on canine testosterone production, it is also possible that such an implant may, in the future, play an important role in the control and management of testosterone-mediated medical and behavioural problems as well. 

This is Suprelorin-12, a 12-monthly slow-release implant used to reduce fertility and unwanted breeding by male dogs.

Canine birth control method 5 - canine vasectomy.

If all you desire is that your male dog not be able to breed with any females inside of or outside of your home, then canine vasectomy is an option for you. Vasectomy is the surgical removal of a section of the male animal's vas deferens or spermatic duct (the tube that takes the sperm from the testicle where it is made, to the lower reproductive tract regions of the prostate and urethra). Without this section of piping, the sperm can not reach the animal's urethra and penis and the animal, therefore, can not get anything impregnated.

Vasectomy is certainly effective at stopping breeding and the passing on of defective genes to any offspring. It will not, however, do anything for that male animal's behaviour or health. Because the testicles are left intact during vasectomy, the animal will still have plenty of testosterone in its body. He will still be inclined towards showing unfavourable male-animal behaviours (roaming, aggression, dominance, territory marking, mounting and copulating with females etc.) and he will still be prone to developing a range of testosterone-mediated health problems.

Author's note: vasectomy is not instantaneous. A vasectomised dog will still be fertile and capable of impregnating bitches for 3 weeks following the procedure. The vasectomised dog should be evaluated by a vet prior to the reintroduction of the dog to any females to ensure that his semen contains no sperm (i.e. that the procedure has been effective). 

Canine birth control method 6 - chemical castration - injecting sclerosing agents into the dog's testes and epididymides.


If all you desire is that your male dog not be able to breed with any females inside of or outside of your home, then chemical castration is an option for you. 

During chemical castration, a sclerosing or scarring agent (e.g. chlorhexidine) is injected into the animal's testis and/or epididymus. This chemical induces a strong inflammatory reaction within the testicle and/or epididymus, resulting in severe scarring of the testis and epididymal sperm ducts such that they do not permit the passage of sperm from the testicle to the lower reproductive tract regions of the prostate and urethra. The sperm can not reach the animal's urethra and penis and the male animal, therefore, can not get anything impregnated. Additionally, the chemically-induced inflammation of the testicle and epididymal tracts exposes the sperm (considered "foreign" cells to the male's immune system) to the animal's immune system. The immune system reacts aggressively against these sperm and all subsequently-made sperm cells, thereby rendering the animal effectively infertile (the immune system "kills off" all the sperm that get made in the future). 

The main side effect of chemical castration is that the process of testicular and epididymal inflammation and scarring is very painful for the animal in the short term. The animal will be expected to have hot, swollen, painful testicles and epididymi for quite a few days after the procedure has been performed. Some animals may suffer severe tissue reactions as a result of this process.

Chemical castration, like vasectomy, is certainly effective at stopping breeding and the passing on of defective genes to any offspring. It will not, however, do anything for that male animal's behaviour or health. Because the testicles are left intact during chemical castration, the animal will still have plenty of testosterone in its body. He will still be inclined towards showing unfavourable male-animal behaviours (roaming, aggression, dominance, territory marking, mounting and copulating with females etc.) and he will still be prone to developing a range of testosterone-mediated health problems.

Author's note: chemical castration is not instantaneous. A chemically castrated dog will still be fertile and capable of impregnating bitches for around 35 days following the procedure. The chemically castrated dog should be evaluated by a vet prior to the reintroduction of the dog to any females to ensure that his semen contains no sperm (i.e. that the procedure has been effective). 

Anti-testosterone agents (e.g. Tardak, MPA-50, Ovarid) used to reduce testosterone-mediated medical and behavioural problems.


All of the alternatives to surgical desexing mentioned thus far (i.e. sections 10a-10f) have pertained to canine birth control and the prevention of unwanted pregnancy. None of them (except perhaps for 10d - also mentioned in this section) have provided any solution to the castration-responsive behavioural and medical problems that are caused or contributed to by the presence of too much testosterone in the animal's bloodstream. As mentioned previously, the problematic testosterone-mediated behavioural issues include: dominance, inter-male aggression, territorial marking, territorial guarding, hypersexual behaviour (chair-leg mounting and toy humping), excessive libido, excessive sexual interest in females and so on. Testosterone-mediated medical problems include: benign prostate hyperplasia, prostatitis, prostatic abscess, perianal adenoma and perianal carcinoma. 

Undesexed animals with significant testosterone-mediated behavioural and/or medical problems should, ideally, be neutered. Desexing is the best way to drop that animal's blood testosterone levels rapidly and permanently and thereby provide some relief and treatment for the medical and/or behavioural issues at hand. 

Owners who are unwilling to desex their animals, however, even in the face of significant testosterone-mediated behavioural and/or medical problems, can make use of various alternative "anti-testosterone" medications as a way of treating or managing these conditions. These anti-testosterone medications are mainly reproductive hormone and reproductive-hormone-like chemicals; with progesterone and progesterone-derived compounds the most frequently used, closely followed by various other drug compounds (e.g. estrogens, GnRH analogues, 5-alpha-reductase inhibitors, testosterone-receptor antagonists).

These anti-testosterone drugs work by either:
a) inhibiting the action of testicularly-made testosterone on cells of the body (e.g. 5-alpha-reductase inhibitor drugs, testosterone-receptor antagonist drugs, progesterone drugs) or by 
b) reducing the production of testosterone altogether (e.g. progesterones, oestrogens, GnRH analogues).
By reducing the production or effect of testosterone on the body, these drugs essentially mimic the effects of neutering as a means of treating or controlling these testosterone-caused medical and/or behavioural conditions. 

Similar to what was discussed in section 10c (hormonally induced estrous suppression in the bitch), the problem with many of these hormonal testosterone-inhibiting solutions is that they can have potentially devastating, life-threatening and/or aesthetically displeasing side effects on the dog. 

Progesterones and progesterone-derivatives:

The progesterone and progesterone-derived drugs commonly used to temporarily or, with repeated use, permanently suppress testosterone production, testosterone action and testosterone-mediated medical and behavioural problems in the male dog include: medroxyprogesterone acetate (MPA), megestrol acetate and delmadinone. Common tradenames include: MPA-50, Ovarid and Tardak.

These progesterone drugs are thought to have several effects on the male reproductive system including the following:

They exert a negative feedback effect (suppressive effect) on testosterone production by the testicles.

They inhibit the enzyme (5-alpha-reductase) responsible for converting the testosterone made by the testicles into its more active, potent form: 5-alpha-dihydrotestosterone (5-DHT).

They reduce or down-regulate testosterone-receptor numbers in certain tissues normally targeted by testosterone (e.g. the cells of the prostate), thereby providing the secreted testosterone molecules with fewer places to bind on to and exert their effect. Put simply, in order for testosterone to have any effect on a cell of the body (e.g. a prostate cell), it must be able to bind onto the surface of that cell first by attaching to a testosterone-receptor. If there are fewer testosterone-receptors available for testosterone molecules to attach on to, the testosterone can not exert its effect on those tissue cell/s.

At normal doses, these drugs have not been found to reduce male fertility or decrease sperm number and nor do they appear to have any significant effect on male libido. Because of this, even though these drugs will reduce certain testosterone-mediated behavioural problems and help to improve or treat medical issues like benign prostate hyperplasia and perianal adenoma, these drugs will not prevent a treated male animal from getting a female animal pregnant. At extremely high doses (higher than recommended), however, progesterones may adversely affect sperm production and motility, resulting in reduced fertility. 

Common side effects of progesterone use in the male dog are similar to those seen in the bitch and include: lethargy (sleepiness); increased appetite; weight gain and, occasionally, loss of hair or change in hair colour and shrinkage of the skin and subcutaneous tissues at the site of injection. Insulin resistance and diabetes mellitus may also be induced by long-term progesterone usage as can growth hormone problems like acromegaly. Progesterones can sometimes mimic the effect of corticosteroids in the dog, resulting in a Hyperadrenocorticism effect (Cushing's disease) and a liver condition called steroid hepatopathy (a liver full of fat). 

Some males treated with progesterone products have been found to develop mammary enlargement, mammary nodules and even nasty mammary tumours (breast cancer). 

Author's note: of all of the progesterone products marketed for this purpose, delmadinone (tradenames include Tardak) and megestrol acetate (tradenames include Ovarid)are the more commonly used. They do have side effects (described above), but these are not too common provided the drug is used according to instructions and not for prolonged periods of time. The use of medroxyprogesterone acetate (MPA), although much safer in the male dog than in the female, is probably better left as a last resort (e.g. if Tardak or Ovarid fails to control prostate hyperplasia, perianal adenomas, hypersexualised behaviours and so on). MPA stays in the body for many months and, because of this, poses a greater risk of producing severe side effects (e.g. diabetes) that are difficult to reverse (the drug, once-injected, can not be taken away). MPA does have an advantage in that a single injection of the compound will have an effect on the testosterone-mediated disorder for many months (i.e. the owner does not have to keep dosing the animal). 

Author's note: An anti-testosterone agent such as progesterone is never going to be as effective at reducing or controlling testosterone-mediated behavioural and medical conditions as neutering will. As long as the testicles remain in place, the drug will only be able to temporarilyhold-off these medical conditions and problem behaviours. These testosterone-induced problems will recur whenever the drug wears off, necessitating that the animal remain on repeated doses of medication for life. This is not only inconvenient and costly for the owner, but it also increases the risk that the animal will develop severe side effects as a result of the ongoing medication. 

Estrogens (oestrogens) and estrogen-derivatives:

The estrogen and estrogen-like drugs most commonly used to temporarily or, with repeated use, permanently suppress testosterone production and testosterone-mediated medical and behavioural problems in the male dog include: diethylstilbestrol (diethylstilboestrol) and estradiol (oestradiol). Common tradenames include: Stilbestrol tablets.

The estrogen drugs exert their negative effect on testicular testosterone production by exerting a negative feedback effect on the pituitary-derived hormone (called luteinising hormone or LH), which is responsible for stimulating the testicles to produce and release testosterone. By reducing or preventing the production of LH, oestrogen essentially prevents the LH-mediated production of testosterone by the testicles.

Currently, estrogen is not recommended for use in the prevention or control of testosterone-mediated medical and behavioural problems in the male dog. Although the hormone is effective at treating such medical issues as benign prostate hyperplasia, the potential side effects of excessive and prolonged estrogen usage in the dog are severe and potentially life-threatening. Side effects of estrogen use include: oestrogen feminising syndrome (male dogs become feminized and feminine in appearance); squamous metaplasia of the prostate (a hormone-induced change in the prostate's structure that makes it less functional and more prone to infection and abscessation) and bone marrow suppression (a complete failure of production of all of the dog's blood cells, which can often be fatal). For further information on oestrogen toxicity, see our great cryptorchidism page.

Author's note: An anti-testosterone agent such as estrogen is never going to be as effective at reducing or controlling testosterone-mediated behavioural and medical conditions as neutering will. As long as the testicles remain in place, the estrogen drug will only be able to temporarilyhold-off these medical conditions and problem behaviours. These testosterone-induced problems will recur whenever the drug wears off, necessitating that the animal remain on repeated doses of medication for life. This is not only inconvenient and costly for the owner, but it also increases the risk that the animal will develop severe side effects as a result of the ongoing medication. In the case of oestrogen, these side effects can be very dangerous for the dog. 

5-alpha-reductase inhibitors:
The 5-alpha-reductase inhibitors are a group of drugs that inhibit the action of the enzyme (called 5-alpha-reductase) responsible for converting the testosterone made by the testicles into its more active, potent form: 5-alpha-dihydrotestosterone (5-DHT). There are several drugs in this class, the most common being finasteride and chlormadinone, and they are currently being used in the control and management of such testosterone-mediated medical problems as benign prostate hyperplasia. In the future, they may also have a role in the control and management of testosterone-mediated behavioural problems. 

Of the two drugs, finasteride is the more commonly used. At normal doses, it does not seem to reduce male fertility or decrease sperm number. Because of this, even though finasteride will improve or treat testosterone-mediated medical issues like benign prostatic hyperplasia, it will not prevent a treated male animal from getting a female animal pregnant. Chlormadinone, on the other hand, has been known to reduce fertility in male dogs and it is therefore less popular.

Author's note: An anti-testosterone agent such as finasteride is never going to be as effective at reducing or controlling testosterone-mediated behavioural and medical conditions as neutering will. As long as the testicles remain in place, the drug will only be able to temporarily hold-off these medical conditions and problem behaviours. These testosterone-induced problems will recur whenever the drug wears off, necessitating that the animal remain on repeated doses of medication for life. This is not only inconvenient and costly for the owner, but it also increases the risk that the animal will develop severe side effects as a result of the ongoing medication.

The testosterone-receptor antagonists:
The testosterone-receptor antagonists are a group of drugs that work by binding-to and blocking-up testosterone-receptors in certain tissues normally targeted by testosterone (e.g. the cells of the prostate), thereby providing the secreted testosterone molecules with fewer places to bind on to and exert their effect. Put simply, in order for testosterone to have an effect on a cell of the body (e.g. a prostate cell), it must be able to bind onto the surface of that cell first. It does this by attaching to a testosterone-receptor on the surface of the cell. If there are fewer testosterone-receptors available for the testosterone molecules to attach on to (because the drug molecules have blocked them up before the testosterone gets to them), then the testosterone will not be able to exert its effect on the target cell/s.

There are several drugs in this class, the most common being flutamide and hydroxyflutamide, and they are currently being used in the control and management of such testosterone-mediated medical problems as benign prostate hyperplasia. In the future, they may also have a role in the control and management of testosterone-mediated behavioural problems as well. 

At normal doses, these drugs (flutamide and hydroxyflutamide) do not seem to reduce male fertility or decrease sperm number, nor do they seem have any significant effect on male libido. Because of this, even though these drugs will improve or treat testosterone-mediated medical diseases like benign prostatic hyperplasia, they will not prevent a treated male animal from getting a female animal pregnant. 
Author's note: An anti-testosterone agent such as flutamide is never going to be as effective at reducing or controlling testosterone-mediated behavioural and medical conditions as neutering will. As long as the testicles remain in place, the drug will only be able to temporarily hold-off these medical conditions and problem behaviours. These testosterone-induced problems will recur whenever the drug wears off, necessitating that the animal remain on repeated doses of medication for life.This is not only inconvenient and costly for the owner, but it also increases the risk that the animal will develop severe side effects as a result of the ongoing medication.

The GnRH analogues - deslorelin:
The GnRH analogues are a group of drugs that produce a negative effect on testosterone production by exerting a negative feedback effect on the pituitary-derived hormone (called luteinising hormone or LH), which is responsible for stimulating the testicles to produce and release testosterone. By preventing the production of LH, GnRH analogues essentially prevent the LH-mediated production of testosterone by the testicles. 

The GnRH analogue most commonly used in Australia is deslorelin (tradename Suprelorin-12). It is currently being marketed as a male form of the "pill". It is a slow-release, 12-monthly, contraceptive implant that suppresses testosterone production to such a low level that canine fertility, sperm production, ejaculation and libido are all but non-existent. The male animal essentially becomes infertile while it has the implant and is unable to father any pups. 

Because of the inhibitory effects of this product on canine testosterone production, it is also possible that such an implant may, in the future, play an important role in the control and management of testosterone-mediated medical and behavioural problems as well.
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