Introduction

When it comes to testosterone replacement therapy (TRT), choosing the right ester can significantly impact the treatment's effectiveness and convenience. Testosterone Propionate, Testosterone Cypionate, and Testosterone Enanthate are three commonly used esters, each with its unique characteristics and benefits. However, Testosterone Propionate has fallen out of favor for long-term TRT due to its short half-life and frequent injection requirements.

In this article, we'll discuss the major differences among these 3 esters in terms of injection frequency, absorption rates, metabolism, and overall efficacy. By understanding these distinctions, you can make a more informed decision about your TRT options and find the most suitable treatment plan for your needs.

But before learning about their differences, let us understand each ester in a little more detail.

What are Testosterone Propionate, Cypionate and Enanthate?

Testosterone Propionate is a short-acting testosterone ester. It has a very short half-life of approximately 2, which means it releases testosterone into the bloodstream quickly and is metabolized rapidly. Due to its short half-life, Testosterone Propionate requires frequent injections, typically every 2-3 days, to maintain stable testosterone levels.

Testosterone Cypionate is a long-acting ester of testosterone. It has a longer half-life than Propionate (about 8 days), which allows for a more gradual release of testosterone into the bloodstream. Because of its longer half-life, Testosterone Cypionate typically requires injections every 1-2 weeks, making it more convenient for patients. The longer duration between injections helps maintain more stable testosterone levels. This reduces the likelihood of mood swings and estrogen-related side effects. For this reason, Cypionate is a preferred choice for many clinicians.

Testosterone Enanthate is another long-acting testosterone ester, similar to Cypionate. It has a half-life of approximately 4.5-8 days, facilitating a slow release of testosterone. Like Cypionate, Testosterone Enanthate is also typically administered every 1-2 weeks. Since it offers a reliable and consistent release profile, it is widely used in TRT to achieve steady testosterone levels.

Why is Testosterone Propionate not Prescribed for Testosterone Replacement Therapy (TRT) like Cypionate and Enanthate?

Testosterone Propionate has fallen out of favor for treating hypogonadism due to its short half-life of 19 hours, requiring frequent injections every 2-3 days for maximum efficacy. (1) Frequent injections increase the risks of aromatisation, supra psychological levels of testosterone, mood swings and more altered sexual behavior due to higher rates of conversion to estrogen. (2) (3) 

The latest contenders are Testosterone Cypionate or Enanthate which have a similar structure but longer hydrocarbon chains, with a longer half-life of 4.5-8 days, requiring injections every 2-3 weeks, and significantly better than propionate injections. (3) (4) (5) (6) Less frequent injections imply minimal, manageable side effects. They have become the most common forms of subcutaneous (SC) or intramuscular (IM) testosterone to manage low testosterone levels, albeit at a proper, regulated dosage. (7)

Also read: Testosterone Cypionate vs Enanthate

Testosterone Cypionate vs Enanthate vs Propionate: The Key Differences

Injection Mode and Frequency

Both testosterone cypionate and enanthate can be injected weekly, biweekly, or monthly. They can also be taken in micro-doses along with HCG (human chorionic gonadotropin) every other day to keep testosterone levels steady, like the body's natural production. HCG is a hormone that helps maintain natural testosterone production while also preserving fertility.

If following the intramuscular dosing regimen, for testosterone cypionate, administration of 50–400 mg every 2–4 weeks will lead to supratherapeutic testosterone levels 4–5 days after dosing and subtherapeutic levels on day 14 post-dosing. For testosterone enanthate, the supratherapeutic testosterone levels spike 36–48 hours post-dosing and subtherapeutic levels by 3–4 weeks post-dosing.(5)

Multiple studies on the safety, management of induced adverse effects, flexibility of dosing frequency, and choice of dosing modalities (IM or SC) of both cypionate and enanthate have made propionate redundant.(5)

Availability

Although testosterone propionate was the very first testosterone ester formulated as intramuscular injections and prescribed for androgen replacement in the 1950s, it is now sold only in compounding pharmacies in the US. Some of the accepted combinations of testosterone propionate contain phenylpropionate, isocaproate, and decanoate.(3) However, compounded formulations are not regulated, have shown mixed performance in efficacy studies, and hence are to be taken only if prescribed. (8)

In contrast, cypionate and enanthate are easily accessible in both generic and branded forms, are regulated by the US FDA under different doses for hypogonadism, with the choice of injecting modalities: intramuscular or subcutaneous.

Propionate is available for veterinary purposes, but commercial propionate for androgen replacement in humans is stopped due to more efficient and safer esters like cypionate and enanthate.

While its properties of quickly peaking in the blood plasma within hours and rapid metabolizing can rapidly increase testosterone levels, the side effects from increased estrogen - gynecomastia, increased fat mass, and oedema counters the benefits. since frequent injections are necessary with a short half-life of 3 to 4 days.

Absorption

Testosterone propionate is absorbed slowly from the intramuscular site of administration owing to a less polar ester group in its chemical structure. This is the reason why multiple injections of testosterone propionate are needed when compared with testosterone enanthate or testosterone cypionate.

On the other hand, testosterone cypionate and enanthate are more polar esters and lipophilic in nature, which is why a subcutaneous dosing helps them get absorbed in fat easily. Hence, subcutaneous injections work better compared to intramuscular doses. Currently, a depot form of injection which allows slow release of the compound is the prevalent dosing form for both testosterone cypionate and enanthate, which also gives them an edge over propionate.(9)

Metabolism

All testosterone esters cleave into free testosterone in blood plasma. Propionate rapidly metabolizes to 17-keto steroids through two different pathways with estradiol and dihydrotestosterone (DHT) as the two key metabolites. Comparatively, cypionate and enanthate are metabolized slowly and produces free testosterone for a longer time for the body to absorb it.(3)

Testosterone Propionate vs. Cypionate: Risk Evaluation

The Testosterone propionate vs. cypionate debate can be sorted in two very important facts: firstly, propionate is a shorter acting compound and hence needs more frequent injections; moreover, compounded formulations available in pharmacies to increase its efficacy are also not regulated and prone to conflicting results. Secondly, men with untreated prostate and breast cancer, are specifically contraindicated against any form of testosterone therapy. Patients with a history of male breast cancer, worsening benign prostatic hyperplasia (BPH), polycythemia peripheral edema, cardiac and hepatic dysfunction, and an increased risk of obstructive sleep apnea (OSA) are also advised to take testosterone therapy only if prescribed. In such cases, frequent injections of testosterone are risky.(10)

Testosterone cypionate has a longer half-life (8 days) in comparison to propionate (19 hours) when injected intramuscularly; in fact, it has one of the longer side chains in the injectable testosterone formulations and is more stable in comparison to propionate. Although if a person is predisposed to the aforementioned conditions, the whole propionate vs. cypionate debate stands nullified, but in hindsight, only patients who are medically described as undergoing either of the following conditions are allowed to consult physicians for any form of androgen therapy:

Primary hypogonadism (congenital or acquired) determined by testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy

Hypogonadotropic hypogonadism (congenital or acquired) determined by idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury as a result of tumors, trauma, or radiation

Where is Testosterone Propionate Still Prescribed for TRT?

Propionate is prescribed in Canada, Europe and a few other countries where it is used in combination with longer acting testosterone esters to avoid peaks and valleys.

Testoviron Depot 50 and 100, is a combination of testosterone propionate and enanthate, whereas Sustanon 100 and 250, combines testosterone propionate, phenylpropionate, isocaproate, and decanoate.(3)

But these combination esters result in higher supra psychological levels of testosterone with no added benefit of longer duration of action, and their efficacy also remains doubtful. Hence compounded formulations should be only resorted to, if and only if, advised by a doctor.

Conclusion

Testosterone replacement therapy is only for those with low testosterone levels with a valid doctor’s prescription. Frequent injections of testosterone should be avoided at all costs, especially for those with prostate and breast cancer complications, and those at risk of blood clots, kidney conditions and some cardiovascular complications. Testosterone propionate half-life is shorter than testosterone cypionate or testosterone enanthate half-life and hence, if necessary, it is always better to go for testosterone cypionate or enanthate.

If you want to get testosterone enanthate or cypionate therapy in Canada (insert appropriate hyperlink) get a questionnaire filled and you can connect to our doctors to guide you through the testosterone replacement therapy process at Science & Humans. (insert appropriate hyperlink)

Learn more about testosterone replacement therapy in Canada.

Frequently Asked Questions about Propionate, Cypionate and Enanthate

Which is Better, Testosterone Cypionate or Propionate?

Testosterone Cypionate is generally preferred by TRT specialists due to its longer half-life (8 days vs. 19 hours), requiring fewer injections (every 1-2 weeks vs. every 2-3 days). This leads to more stable testosterone levels and fewer side effects.

Is Enanthate Better than Propionate?

Testosterone Enanthate is generally preferable to Propionate for TRT because it requires less frequent injections. Enanthate can be injected every 1-2 weeks, while Propionate needs injections every 2-3 days. This makes Enanthate more convenient and easier to maintain stable testosterone levels.

Can You Mix Cypionate and Propionate?

In theory, you could mix Testosterone Cypionate and Propionate. This combination can cause a rapid initial peak from Propionate, followed by a sustained release from Cypionate, providing both immediate and prolonged testosterone levels. But you must always consult your doctor for personalized advice.

Is there a testosterone enanthate/cypionate/propionate blend to try for better outcomes?

Any compounded formula for testosterone is not regulated by any medical body, because their efficacy is still under significant doubt. Moreover, to think that higher doses of testosterone in compounded forms can lead to improved testosterone levels and cure hypogonadism is not ideal since all forms of testosterone come with their own quota of adverse effects and risks. These medications are prescribed only on personalized treatment plans from experts. 

Between testosterone propionate vs cypionate bodybuilding is benefited by which ester?

The use of any form of steroid for any recreational or athletic activity is not regulated and is not endorsed by any manufacturer. It is dependent on the individual and their doctors. Please refrain from using any testosterone ester for any form of athletic or recreational purpose unless strictly prescribed by the doctor for clinical purposes.