Testosterone Supplementation

Hormone Balancing

Many vets are not familiar with hormone balancing, but they can do well once they familiarize themselves with the products available to them. It’s just a matter of developing a comfort level with what works for each vet, dog and guardian. We are not vets and you will need to develop a working relationship with a vet in order to balance your dog’s hormones effectively. We provide this information to help flatten the learning curve for the vet and the guardian who are new to this.

The first ground rule is that you want to supplement to normal physiologic levels of any hormone. Essentially, you want to bring the dog’s hormone levels to where they would have been had they never been altered. This necessitates testing to determine hormone levels once hormone imbalance is suspected. Please see our FAQ item #3 for specific information as to where your dog’s blood sample may be sent for hormone testing. You do want to check levels of testosterone, estradiol (estrogen) and progesterone.

As we have discussed repeatedly on this website, hormonal treatment for dogs is modeled after protocols developed for humans. We recommend measuring fasting morning (before 10AM) total T concentrations using an accurate and reliable assay as the initial diagnostic test. Initiation of testosterone replacement therapy (TRT) is usually driven by patient symptoms in addition to low serum level.²⁰⁸^,²¹⁴ For our dog Billy, testosterone cypionate was injected intramuscularly (e.g. in the muscle of a rear leg), once a month. This was an experimental protocol, recommended by a veterinary professor in Colorado approximately 9 years ago.

There are currently over 30 different testosterone preparations approved for use by the United States Food and Drug Administration.²⁰⁸ With respect to dogs, many of the topical preparations are not feasible, due to the lowered absorption through fur, and the risk of dermal transmission to other dogs or children. Injectables are the favored method of supplementation, with subcutaneous preferred over intramuscular.

Today, Testosterone Cypionate is the most commonly prescribed form of testosterone replacement in the United States of America. Currently the recommendation for humans is to inject testosterone cypionate subcutaneously once a week. This protocol is utilized in humans because it provides favorable outcomes in terms of less pain than intramuscular administration, consistent and stable testosterone levels, and ease of home administration.²⁰⁹^,²¹⁰ This protocol was applied in a recent case study²¹¹ for testosterone supplementation in a symptomatic male, neutered dog. Testosterone cypionate was injected subcutaneously. The initial dosing was 1.7 mg/kg once a month, and transitioned to a weekly dose of 0.5 mg/kg to maintain testosterone levels equivalent to an intact male dog. We point out that the weekly dose is preferable, and that this is an injection a dog owner should be able to accomplish, much as dog owners are trained by vets to inject insulin when a dog has become diabetic. This case study is valuable to the veterinary practitioner as well as the pet guardian, as it reviews the rationale for supplementation and provides facts that can become the basis for appropriate “informed consent”. Considering testosterone replacement therapy is a relatively new procedure for most veterinary professionals, the inclusion of options for administration, risks and intended benefits is extremely beneficial. The authors also describe how they addressed a condition (elevated LH concentration) which did not respond to supplementation as hoped.

It should be mentioned that subdermal testosterone pellets were the first effective formulation for androgen replacement therapy, developed in the 1940s. Testosterone pellets consist of crystalline testosterone and are created through high-temperature molding and designed for consistent and prolonged release. Absorption occurs through uniform erosion of the pellet’s surface in correspondence to the solubility of testosterone in extracellular fluid. We would recommend utilizing injections to determine the appropriate dose for each dog. Once that has been established, testosterone pellets are available generically in 12.5, 25, 37.5, and 50 mg pellets. A 75 mg pellet is also available as Testopel^® (Auxilium Pharmaceuticals Inc., Malvern, PA, USA). The most common adverse event is pellet extrusion, with an incidence of 10%. Other adverse events include site infections, bleeding, and fibrosis at the insertion site. Potential advantages of pellet usage include the infrequency of dosing, guaranteed compliance, and lack of transference. However, administration is invasive requiring skin incision and local anesthesia.²⁰⁸

Testosterone is available in different formulations, and this varies with where you are in the world. Many places in the world prefer the very similar injectable Testosterone Enanthate to Testosterone Cypionate. There are also blended formulations of testosterone which offer the advantage of stepped release to theoretically provide a more constant level of testosterone with less frequent injections.

DURATESTON 50 includes per ml:

testosterone propionate 6 mg (short-acting)
testosterone phenylpropionate 12 mg (medium to long-acting)
testosterone methylpantanoate 12 mg
testosterone decanote 20 mg (medium to long-acting)

It’s big brother SUSTANON 250 is an oil-based injectable containing four different testosterone compounds:

testosterone propionate 30 mg (short-acting)
estosterone phenylpropionate 60 mg (medium to long-acting)
testosterone isocaproate 60mg (medium to long-acting)
testosterone decanoate 100 mg (medium to long-acting)

(Side effects of Sustanon are, for the same amount of testosterone, identical to other testosterone esters such as testosterone enanthate. The dose rate for the Sustanon 250 reported to us by vets is 0.1-0.2ml/10kg.)

OMNADREN – per ampoule of 250mg/ml:

testosterone propionate 30 mg (short-acting)
testosterone phenylpropionate 60 mg (medium to long-acting)
isocaproate 60mg (medium to long-acting)
testosterone caproate 100 mg (medium to long-acting)

Some guardians want to avoid injections. In some areas of the world oral testosterone formulations are available, but due to their propensity to create liver damage they are not approved for use in the USA. Accordingly, testosterone pellets may be the best option (see above).

ESTRADIOL (ESTROGEN) IN HORMONE BALANCING FOR MALE DOGS

We want to emphasize the importance of testing for estradiol/estrogen in male dogs as well. As early as 1939, the Canadian Journal of Comparative Medicine published a paper reporting on three case studies²¹² of male dogs who presented with inflammation of the genital tract which could not be attributed to any infectious process. It was postulated that one of the roles of testosterone is to neutralize the effects of estrogens in male dogs. In short, they recognized there may be an ideal ratio of testosterone/estrogen which facilitates optimal health. However, in 1939 there was no discussion of any means to reduce the level of estrogens. Therefore, the practitioners chose to treat the dogs with supplemental injections of testosterone propionate to see if these inflammatory conditions in the three canine cases were due to dominance of estrogens. By treating a purported testosterone deficiency in these dogs they could effectively change the ratio of testosterone to estrogen. In all three cases, the testosterone propionate resolved the inflammatory processes. It was noted also, that the resolution was not permanent, and periodic injections of testosterone propionate were required to prevent re-occurrence of the inflammatory processes.

Over time we have come to understand that in men estradiol arises from the peripheral aromatisation of testosterone (T), and estradiol is considered to have many opposing physiological functions with respect to testosterone (much as postulated in 1939). We find the progressive T decline in the aging male is associated with relative and/or absolute increase in serum estradiol (E₂).²¹⁶

In 2021, a study was performed in Brazil wherein the goal was to quantify the testosterone/estradiol ratio for optimal health in men known to be suffering from low testosterone levels. In this study, the frequency of morning erections (≥3/week), was utilized as a tangible measurement to assess functional hormonal health. It was concluded that a ratio of 12/1 testosterone to estradiol was ideal. If we are to replicate the ideal 12/1 ratio of testosterone to estradiol in hormone balancing for the neutered male dog, we must remember the main source of estradiol production in males occurs through peripheral aromatization of testosterone in fatty tissue, so replacing testosterone can also result in replenishing estradiol.²¹³

To complicate this issue of excess estradiol, there is a significant percentage of neutered male dogs who exhibit symptoms of hormonal imbalance and when tested for endocrine imbalance have a significantly increased level of estradiol (without testosterone supplementation). From a 2007 presentation⁷⁶ given by Dr. Jack W. Oliver:

“Hyperestrinism in dogs may be a new and emerging disease entity. In sample submissions to the Clinical Endocrinology Service (2005) at The University of Tennessee, 40% of adrenal panels had elevated estradiol levels present...Effective treatment options for hyperestrinism in dogs is limited at the present time…”

For example, our dog Billy’s adrenal panel at the University of Tennessee had 5-6x the normal amount of estradiol for a male dog, and NO testosterone. Imagine how far from the desired testosterone/estradiol ratio he was–no surprise to us, because he was very sick. This adrenal panel finally provided an explanation for his constellation of maladies–early age neutering destroyed his hormonal balance. We could not supplement Billy with enough testosterone to reach the desired ratio of 12/1; we needed to reduce his estradiol as well. At the time, the only recommendation from U. Tennessee to reduce estradiol was large doses of melatonin. However, Billy had already been on melatonin for years before his adrenal panel at U Tennessee showed him to have 5-6x the normal estradiol. Clearly melatonin does not work, and it does have side effects, the most serious is that it affects the action of insulin, and in Billy’s case it caused him to develop poorly controlled type 2 diabetes.

We have the means to reduce the level of estradiol and/or supplement the level of testosterone. Vets at the time and even now do not routinely offer a solution (excepting melatonin) for Billy’s (or other neutered male dogs’) excess estradiol. We did our own intensive research for an extended period of time to see if we could identify a means to prevent the creation of estradiol from testosterone. We found ourselves exploring the five or so compounds utilized to block the creation of estradiol in women who were battling estrogen-sensitive breast cancer. The enzyme that facilitates this process is aromatase. So, if we could block the activity of aromatase, we could block the creation of estradiol.

We evaluated the first, second and third generation aromatase inhibitors for their efficacy, side effects and potential danger to dogs (as compared to women). First generation and second generation aromatase inhibitors were relatively weak and nonspecific. Nonspecific in the respect that they blocked estradiol production but they also inhibited other enzyme systems involved in steroid biosynthesis and therefore had other undesirable side-effects. We settled on a third-generation aromatase inhibitor, anastrozole. Anastrozole is potent and does not inhibit related enzymes. It is well tolerated and apart from its desired effects on estradiol metabolism its use does not appear to be associated with important side effects. Although aromatase inhibition by anastrozole is reported to be close to 100%, administration of anastrozole to human males does not suppress plasma estradiol levels completely.²¹⁸ This is desirable–remember the 12/1 ratio is ideal for health. We were not sure the same would be true for male dogs because there is one important variable–men involved in studies had their testes, our dogs do not. Our confidence was boosted when we discovered anastrozole was reversible in its action, and had been tested in beagle dogs to establish its efficacy and safety (for humans). At our request, the specialty vet prescribed anastrozole for Billy, and it worked beautifully. In conjunction with anastrozole, we supplemented with testosterone and Billy’s estradiol levels stayed low while his testosterone levels came up to normal.