Testosterone replacement therapy (TRT) is used to treat testosterone deficiency, which affects around 10% of men worldwide and as many as 40% of men over the age of 45. TRT can improve the quality of life for men with low testosterone. It’s also used as a form of cross-sex hormone therapy for trans men.
Testosterone undecanoate (TU) and testosterone enanthate (TE) are two common forms of testosterone used for TRT and cross-sex hormone therapy. Testosterone enanthate is an injectable ester that’s shorter-acting than testosterone undecanoate, which comes in both oral and longer-acting injectable forms. There are many similarities and differences between testosterone undecanoate vs enanthate.
This article will compare and contrast TU and TE in terms of:
- how well they work
- safety
- how they’re taken
- who they’re most appropriate for
The goal is to provide doctors with the information they need to decide which form of testosterone is best for their patients.
Pharmacokinetics and Administration
The way your body absorbs, uses, and gets rid of testosterone, along with how often you need to take it, differs quite a bit between testosterone enanthate and testosterone undecanoate. Let’s break it down:
Testosterone Enanthate (TE)
If your doctor prescribes testosterone enanthate, you’ll get it via an intramuscular injection – a shot directly into a muscle.
Administration Route and Frequency
Because TE has a shorter half-life (meaning it gets cleared from your body faster), you’ll typically need injections every 2-4 weeks to keep your testosterone levels steady.
Pharmacokinetics
TE gets absorbed and converted into testosterone pretty quickly after the injection. However, that also means you need those more frequent injections to avoid dips in your testosterone levels.
Testosterone Undecanoate (TU)
Testosterone undecanoate offers more options in how you take it, which affects how your body handles it.
Oral Formulations: Administration and Absorption
You can take TU orally (as a pill) under several brand names like Andriol, Jatenzo, Tlando, and Kyzatrex. The big thing with oral TU is that it’s absorbed through your lymphatic system (a network of vessels that helps with immunity and fluid balance).
The amount of fat in your diet really impacts how well your body absorbs oral TU. Some formulations, like Jatenzo, use special self-emulsifying systems to help with absorption even if you’re not eating a super high-fat meal. Tlando is designed to deliver a consistent dose without needing adjustments. Kyzatrex uses phytosterols to maximize how much gets absorbed through the lymphatic system.
Injectable Formulations: Administration and Absorption
Injectable TU, sold under brands like Aveed and Nebido, is a long-acting form. This means you only need an intramuscular injection every 10-14 weeks.
Because it’s long-acting, injectable TU provides much more stable testosterone levels compared to TE. The longer half-life means fewer ups and downs.
Efficacy in treating testosterone deficiency
Both testosterone enanthate (TE) and testosterone undecanoate (TU) are prescribed to treat hypogonadism in men. But how well do they work?
TE Efficacy
Restoring Testosterone Levels
TE is effective at raising testosterone levels in men with low T. However, it’s important to get your levels checked to make sure they stay within the normal range.
Symptom Improvement
TE can improve the symptoms linked to low testosterone, such as:
- Low sex drive
- Fatigue
- Muscle loss
TU Efficacy
Oral TU: Restoring Testosterone Levels
Oral TU medications like Jatenzo, Tlando, and Kyzatrex have been shown to be effective at restoring healthy testosterone levels in most patients. Studies show that 84% to 88% of men taking oral TU saw their testosterone levels return to normal.
Injectable TU: Restoring Testosterone Levels
Injectable TU medications like Aveed and Nebido are effective at keeping testosterone levels stable and within a healthy range for long periods of time. For example, one study showed that Aveed helped men reach an average testosterone concentration of 890.6 ng/dL.
Symptom Improvement
Both oral and injectable TU medications improve the symptoms related to low testosterone levels.
SAFETY AND ADVERSE EFFECTS
Like any medication, both testosterone enanthate (TE) and testosterone undecanoate (TU) come with potential side effects and safety considerations. It’s crucial to have a frank discussion with your doctor about these risks before starting testosterone therapy.
TE Safety Profile
Common Side Effects
With TE, some of the more commonly reported side effects include:
- Injection site reactions: Redness, pain, or swelling at the injection site are possible.
- Mood swings: Because TE can cause testosterone levels to fluctuate, some men may experience mood swings or irritability.
- Erythrocytosis: TE can increase red blood cell count.
Cardiovascular Risks
The potential for increased cardiovascular risk with TE is a topic of ongoing debate. It’s generally recommended that men on TE therapy have their blood pressure and cholesterol levels monitored regularly.
TU Safety Profile
Oral TU: Safety Considerations
Oral TU is generally considered to be well-tolerated. However, it can potentially lead to increased blood pressure and hematocrit (the percentage of red blood cells in your blood). Your doctor will likely monitor these levels during treatment.
Injectable TU: Pulmonary Oil Microembolism (POME)
Injectable TU formulations, such as Aveed, carry a risk of pulmonary oil microembolism (POME). POME is a rare, but serious, adverse event. Post-marketing analysis of Aveed shows a POME rate of less than 0.1%. Because of this risk, injectable TU must be administered by a healthcare professional who is trained to recognize and manage POME.
General Considerations for Both TU and TE
Both TU and TE can affect your lipid profile, potentially increasing total cholesterol, LDL (“bad”) cholesterol, and triglycerides, while slightly reducing HDL (“good”) cholesterol, similar to the effects of DHT Propionate. Your doctor should monitor your cholesterol levels during testosterone therapy, regardless of the specific ester used.
Use in trans men
Both testosterone enanthate (TE) and testosterone undecanoate (TU) are prescribed as part of gender-affirming care for trans men, though other hormone therapies like estrogen methyltestosterone also play a role in hormonal treatments.
Efficacy in achieving masculinization
Both TE and TU are effective at helping trans men achieve a more masculine appearance. These medications can result in:
- voice deepening
- increased muscle mass
- facial hair growth
Safety and tolerability
Research shows that both TU and TE have comparable effects on hemoglobin, hematocrit, and lipid profiles. Studies have also indicated that both treatments are safe and effective for trans men over a 5-year period.
Both treatments result in increased lean body mass, which contributes to a more masculine physique.
One study found that global satisfaction increased at both 1 year and 5 years in trans men using either TE or TU.
Amenorrhea
Many trans men seek hormone therapy to stop menstruation. Research shows that both TU and TE formulations are effective in achieving amenorrhea in trans men within one year.
Patient selection and individualized treatment
The type of testosterone treatment you and your doctor choose should be based on your individual needs and preferences.
Factors to consider
It’s a good idea to think about the following factors before you and your doctor make a decision:
- Patient preference: Do you prefer frequent injections, less frequent injections, or an oral medication?
- Lifestyle and adherence: Will your lifestyle allow you to stick to a specific injection schedule or medication regimen? Are there factors that might make one treatment option more convenient or difficult than another? Are you, for example, someone with a chronic condition that already impacts your mobility?
- Medical history: Do you have any existing health conditions or risk factors that might make one treatment option less safe for you?
- Cost and availability: How much does each treatment option cost, and is it readily available in your area?
Individualized approach
The best treatment choice is one that’s tailored to your unique needs and preferences. This means having an open and honest discussion with your doctor about the potential benefits and risks of each option.
Once you start treatment, it’s essential to have regular checkups to monitor your testosterone levels, red blood cell count (hematocrit), cholesterol levels (lipid profiles), and blood pressure. These checkups will help your doctor ensure that the treatment is working effectively and that you’re not experiencing any adverse side effects.
Frequently Asked Questions
Can you build muscle with testosterone undecanoate?
Absolutely. Testosterone undecanoate, like other forms of testosterone, can definitely help you build muscle. It increases protein synthesis, which is essential for muscle growth. However, just taking testosterone isn’t enough; you’ll still need to combine it with a proper diet and a consistent workout routine.
What is the difference between test E and test C?
Testosterone enanthate (Test E) and testosterone cypionate (Test C) are very similar. The main difference is the ester attached to the testosterone molecule, which affects how quickly the testosterone is released into the bloodstream. Some people find they respond slightly better to one versus the other, but for most, the effects are nearly identical.
What is the gold standard for TRT?
There isn’t a single “gold standard” for Testosterone Replacement Therapy (TRT), as the best approach depends on the individual. However, injectable testosterone, like testosterone enanthate or cypionate, is often considered a reliable and effective option. Gels and creams are also used, but absorption can be variable. Always talk with your doctor to determine what’s right for you.
How long does test E take to kick in?
Testosterone enanthate typically starts to show noticeable effects within a few weeks. While you might feel some initial changes relatively quickly, it usually takes around 4-6 weeks to experience the full benefits, such as increased energy, improved mood, and muscle growth.
What is the equivalent of testosterone undecanoate?
The “equivalent” dose of testosterone undecanoate depends on the formulation (oral or injectable) and individual response. There isn’t a direct 1:1 conversion to other testosterone esters like enanthate. It’s essential to work closely with a healthcare professional to determine the correct dosage of any testosterone product to achieve the desired therapeutic effects while minimizing potential side effects. They will monitor your testosterone levels and adjust the dosage accordingly.
In Summary
Testosterone enanthate (TE) and testosterone undecanoate (TU) are both forms of testosterone replacement therapy (TRT), but they have some key differences that can influence which one is right for you.
TE requires more frequent injections to maintain stable testosterone levels. TU, on the other hand, comes in both an oral form and a long-acting injectable form, offering more flexibility. However, the oral form of TU needs to be taken with dietary fat to be absorbed properly. The injectable form of TU carries a risk of pulmonary oil microembolism (POME), a rare but potentially serious complication.
When deciding between TE and TU, clinicians need to carefully weigh the differences in how the body processes each drug, as well as their safety profiles and what the patient prefers. Treatment plans should be customized to the individual, and regular monitoring is essential to make sure the treatment is working well and to minimize any risks.
Looking ahead, more research is needed to fully understand the long-term effects of different testosterone formulations on the heart. In addition, ongoing development of new ways to deliver testosterone may lead to even more convenient and effective options for patients in the future.