What is the preferred route of administration for testosterone replacement therapy, topical or oral?

From the Guidelines

Topical testosterone is the preferred route of administration for testosterone replacement therapy compared to oral formulations. This is based on the most recent and highest quality study available, which suggests that topical testosterone formulations, such as gels, solutions, and transdermal patches, provide more stable hormone levels throughout the day and are generally better tolerated than oral testosterone 1.

The benefits of topical testosterone include:

• Bypassing first-pass liver metabolism, which reduces the risk of liver toxicity and provides more stable hormone levels throughout the day
• Clinical improvements in symptoms appearing within 3-6 months
• Convenience and ease of use, with most patients preferring topical gels over injections or patches due to their non-staining and easy-to-use nature 1

However, it's essential to consider the potential risks and limitations of topical testosterone, including:

• Skin-to-skin transfer of testosterone to others, particularly women and children
• Variable absorption rates, which can lead to inconsistent testosterone levels
• Potential skin irritation at the site of application

Regular monitoring of testosterone levels, hematocrit, PSA, and lipid profiles is necessary regardless of administration route to ensure safe and effective treatment 1.

In terms of patient preferences, most men prefer topical gels due to their convenience, ease of use, and non-staining properties 1. However, individual preferences may vary, and the choice of formulation should be based on a discussion between the patient and their healthcare provider.

Overall, the current evidence supports the use of topical testosterone as the preferred route of administration for testosterone replacement therapy, due to its stability, convenience, and safety profile 1.

From the FDA Drug Label

Testosterone gel 1.62% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired). Testosterone gel 1.62% should be applied to clean, dry, intact skin of the shoulders and upper arms.

The preferred route of administration for testosterone replacement therapy is topical, as indicated by the drug label for testosterone gel 1.62%. There is no mention of oral administration in the provided drug labels. Topical administration is the recommended route for this specific product. 2

From the Research

Testosterone Replacement Therapy Routes

The preferred route of administration for testosterone replacement therapy can vary depending on several factors, including patient preference, lifestyle, and medical history.

• Topical testosterone preparations, such as transdermal patches and gels, have been available for several decades and offer a convenient and relatively safe option for patients 3, 4, 5.
• Oral testosterone undecanoate is another option, but its use has been limited due to concerns about hepatotoxicity, although newer formulations have shown improved safety profiles 6.
• Parenteral testosterone esters, such as testosterone enanthate and cypionate, are commonly used, but can result in fluctuating plasma testosterone levels 3, 4.
• Subcutaneous testosterone implants and oromucosal testosterone preparations are also available, but their use is not as widespread 3, 4, 5.

Advantages and Disadvantages of Topical vs Oral Testosterone

• Topical testosterone preparations offer a relatively stable and physiological level of testosterone, with fewer fluctuations compared to oral or parenteral routes 3, 4, 5.
• However, topical preparations can pose a risk of secondary transfer to others, such as spouses or children, which can lead to precocious puberty or other adverse effects 7.
• Oral testosterone undecanoate has the advantage of being a convenient and relatively easy to administer option, but its use has been limited due to concerns about liver toxicity, although newer formulations have shown improved safety profiles 6.

Patient Considerations

• Patient compliance and lifestyle should be taken into account when selecting a testosterone replacement therapy route 3, 4, 5.
• The risk of adverse effects, such as those on the prostate, cardiovascular system, and erythropoiesis, should also be considered, particularly in older patients 3, 4.
• Patient education and reassurance regarding the safety of oral testosterone undecanoate formulations are essential to ensure informed decision-making and adherence to treatment 6.