Testosterone Undecanoate: The Oral and Long-Acting Option

Written by Adam Maggio | Medically reviewed by Dr. Mitchell Ross, MD, ABAARM

Testosterone Undecanoate: The Oral and Long-Acting OptionTestosterone Replacement Therapy (TRT) offers various formulations, each with distinct pharmacokinetic profiles and administration routes. Among these, Testosterone Undecanoate stands out for its unique characteristic as both an oral and a long-acting injectable option. While oral testosterone formulations have historically been associated with hepatotoxicity, a specific oral version of testosterone undecanoate has been developed to bypass

Testosterone Undecanoate: The Oral and Long-Acting Option

Testosterone Replacement Therapy (TRT) offers various formulations, each with distinct pharmacokinetic profiles and administration routes. Among these, Testosterone Undecanoate stands out for its unique characteristic as both an oral and a long-acting injectable option. While oral testosterone formulations have historically been associated with hepatotoxicity, a specific oral version of testosterone undecanoate has been developed to bypass this concern. The injectable form, on the other hand, provides extended duration of action, reducing injection frequency.

Oral Testosterone Undecanoate (Jatenzo, Kyzatrex, Tlando)

Traditional oral testosterone preparations (e.g., methyltestosterone) were often hepatotoxic due to their alkylation at the 17-alpha position, leading to liver strain and damage. Testosterone undecanoate, however, is formulated to be absorbed via the lymphatic system, bypassing first-pass metabolism in the liver. This significantly reduces the risk of hepatotoxicity, making it a safer oral option. It is typically taken with food, as dietary fat aids in its absorption.

Dosing: Oral testosterone undecanoate is usually prescribed in doses ranging from 158 mg to 396 mg per day, divided into two doses (e.g., 158 mg twice daily). The exact dosage depends on individual response and target testosterone levels. Due to its relatively short half-life compared to injectable forms, consistent daily dosing is crucial to maintain stable serum testosterone concentrations.

Pros:

• Non-injectable, appealing to those with needle aversion.
• Avoids liver toxicity associated with older oral testosterone.
• Convenient for daily use.

Cons:

• Requires twice-daily dosing, which can impact adherence.
• Higher cost compared to generic injectable testosterone esters.
• Potential for more fluctuating testosterone levels compared to steady-state injectables.
• Gastrointestinal side effects can occur.

Injectable Testosterone Undecanoate (Aveed, Nebido)

The injectable form of testosterone undecanoate is characterized by its extremely long half-life, allowing for infrequent intramuscular injections. It is dissolved in castor oil and administered deeply into the gluteal muscle.

Dosing: After an initial loading phase, injections are typically given every 10-14 weeks. A common protocol involves an initial injection of 750 mg, followed by a second 750 mg injection four weeks later, and then 750 mg every 10-14 weeks thereafter. This extended dosing interval is a significant advantage for patient convenience.

Pros:

• Very infrequent injections (every 2-3 months).
• Maintains stable testosterone levels over long periods, minimizing peaks and troughs.
• High patient satisfaction due to convenience.

Cons:

• Requires deep intramuscular injection, often administered by a healthcare professional.
• Potential for pulmonary oil microembolism (POME) reactions, though rare, which can cause cough, dyspnea, and dizziness immediately post-injection.
• Slow onset of action, requiring a loading dose.
• Higher cost per dose compared to shorter-acting esters like cypionate or enanthate.

Monitoring and Considerations

Regardless of the formulation, regular monitoring of testosterone, estradiol, hematocrit, and prostate-specific antigen (PSA) is essential. For oral undecanoate, liver function tests are generally not required due to its lymphatic absorption, but baseline and periodic checks may still be performed. For injectable undecanoate, monitoring is crucial to ensure levels remain within the physiological range throughout the extended dosing interval. Testosterone undecanoate offers valuable alternatives for TRT, particularly for those seeking non-daily or highly infrequent administration, provided the unique pharmacokinetic and safety considerations are understood and managed by a knowledgeable practitioner.