What are the most effective topical testosterone (T) replacement therapies for treating hypogonadism?

From the Guidelines

Topical testosterone replacement therapies, such as AndroGel (1% or 1.62%), Testim (1%), Fortesta (2%), and Axiron (2%) solutions, are the most effective options for treating hypogonadism in men, as they provide more stable hormone levels and are generally preferred by patients due to their convenience and ease of use 1.

Key Considerations

• These topical therapies are applied daily to clean, dry skin, with dosing typically starting at 50-100 mg of testosterone daily and adjusted based on blood testosterone levels measured 2-4 weeks after starting therapy.
• Important considerations include avoiding skin-to-skin contact with others, especially women and children, for several hours after application to prevent testosterone transfer, and ensuring the application site is completely dry before dressing.
• Side effects may include skin irritation, acne, increased PSA levels, and potential cardiovascular risks, highlighting the need for regular monitoring of testosterone levels, hematocrit, PSA, and liver function during treatment.

Patient Preferences and Outcomes

• Studies have shown that patients prefer topical gels over injections or patches due to their convenience, ease of use, and non-staining of clothes 1.
• Testosterone treatment has been found to improve vitality and fatigue, as well as depressive symptoms, although the evidence is graded as low certainty due to imprecision and low event rates 1.
• Observational studies have shown no increased risk for mortality, cardiovascular events, prostate cancer, or pulmonary embolism or deep venous thrombosis with testosterone treatment, although long-term safety evidence is lacking 1.

Comparison to Injections

• Topical options provide more stable hormone levels compared to injections, but require daily application and are generally more expensive.
• Injections, on the other hand, may be less expensive but can result in fluctuating serum testosterone levels and require intramuscular administration 1.

From the FDA Drug Label

INDICATIONS AND USAGE 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). Hypogonadotropic hypogonadism (congenital or acquired).

The most effective topical testosterone replacement therapies for treating hypogonadism include testosterone gel 1.62%, as indicated in the drug labels 2, 2, and 2.

• The starting dose of testosterone gel 1.62% is 40.5 mg of testosterone, applied topically once daily in the morning.
• Dose adjustment can be made between a minimum of 20.25 mg of testosterone and a maximum of 81 mg of testosterone, based on the pre-dose morning serum testosterone concentration.
• Application site should be clean, dry, intact skin of the shoulders and upper arms.
• Key warnings include the risk of secondary exposure to testosterone, venous thromboembolism, and increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy.

From the Research

Effective Topical Testosterone Replacement Therapies

The most effective topical testosterone (T) replacement therapies for treating hypogonadism include:

• Testosterone gels, which offer the potential for convenience and ease of administration, as well as flexible dosing regimens 3
• Hydroalcoholic gel containing 1% testosterone, which has proven to be as efficient as a testosterone patch, but with fewer side-effects and a higher grade of patient satisfaction 4
• A new 2% testosterone gel formulation, which has a favorable efficacy and safety profile, and helps alleviate the signs and symptoms of testosterone deficiency 5

Characteristics of Effective Therapies

Effective topical testosterone replacement therapies should have the following characteristics:

• Ability to restore testosterone levels to mid-normal physiological levels 3, 5
• Flexible dosing regimens to accommodate individual patient needs 3
• Minimal side-effects and nuisance problems 3, 4
• High patient satisfaction 4

Monitoring and Dosage

Monitoring of testosterone replacement therapy with transdermal gel is crucial to bring and maintain serum T levels in the normal physiologic range 6. The dosage of topical testosterone gel can be adjusted based on serum testosterone levels, with assessments at peak and minimum levels providing a finely tailored treatment for hypogonadal men 6. A compounded testosterone 5% topical gel has been shown to be clinically effective in improving hypogonadal symptoms and achieving optimal serum total testosterone levels 7.

Forms of Testosterone Replacement Therapy

Different forms of testosterone replacement therapy are available, including:

• Transdermal testosterone gels, which are commonly used in clinical practice 6
• Compounded testosterone topical gels, which can be personalized to individual patient needs 7
• Testosterone patches, which have been shown to be less effective and have more side-effects than hydroalcoholic gel 4