Is oral testosterone therapy safe?

by: Payam Hakimi
May 2025
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Oral testosterone therapy, specifically oral testosterone undecanoate (TU), has been evaluated for its safety and efficacy in treating hypogonadism. According to the Endocrine Society Clinical Practice Guideline, testosterone therapy in general is associated with several potential adverse effects, including erythrocytosis, acne, breast tenderness, and a small decrease in high-density lipoprotein cholesterol levels.[1]

A two-year study on oral TU (JATENZO) demonstrated that it effectively maintained total testosterone concentrations within the eugonadal range and improved psychosexual function without significant changes in liver function or prostate-specific antigen levels.[2] However, typical testosterone-induced safety changes were observed, including a slight increase in systolic blood pressure and hematocrit levels.[2]

The American College of Physicians suggests that clinicians discuss the potential benefits and harms of testosterone treatment with patients, particularly those with age-related low testosterone and sexual dysfunction.[3] They also recommend reevaluating symptoms periodically and discontinuing therapy if no improvement is observed.[3]

In summary, oral testosterone therapy is generally safe when monitored appropriately, but it carries potential side effects such as erythrocytosis, increased blood pressure, and changes in lipid profiles. Regular monitoring of testosterone levels, hematocrit, and prostate-specific antigen is essential to mitigate risks.[1-3]

Oral testosterone therapy, specifically oral testosterone undecanoate (TU), offers a convenient alternative to other forms of testosterone replacement therapy (TRT) such as intramuscular injections, transdermal patches, and gels. However, the benefits and potential side effects of oral TU must be carefully considered in comparison to these other forms.

Benefits of Oral Testosterone Therapy:

• Convenience: Oral TU is easier to administer compared to injections and does not require the daily application of gels or patches.

• Efficacy: Studies have shown that oral TU can effectively maintain serum testosterone levels within the eugonadal range and improve psychosexual function.

Potential Side Effects:

• Erythrocytosis: All forms of TRT, including oral TU, are associated with an increase in hematocrit levels. A systematic review and meta-analysis found that oral TU results in a statistically significant increase in mean hematocrit (4.3%, 95% CI 0.7-8.0). The Endocrine Society recommends monitoring hematocrit levels and managing erythrocytosis through dose adjustments or therapeutic phlebotomy.

• Increased Blood Pressure: Oral TU has been associated with a slight increase in systolic blood pressure (3-6 mm Hg).

• Lipid Profile Changes: Oral TU can lead to a decrease in high-density lipoprotein (HDL) cholesterol levels, similar to other forms of TRT.

Comparison to Other Forms of TRT:

• Intramuscular Injections: These are associated with higher peaks and troughs in testosterone levels, which can lead to more pronounced side effects such as erythrocytosis. However, they may offer greater musculoskeletal benefits due to higher doses.

• Transdermal Patches and Gels: These provide more stable testosterone levels but require daily application and can cause skin irritation.

In summary, oral testosterone therapy offers a convenient and effective option for TRT, but it shares common side effects with other forms, including erythrocytosis, increased blood pressure, and changes in lipid profiles. Regular monitoring and individualized dose adjustments are essential to mitigate these risks.