What is the preferred route of administration for testosterone replacement therapy, topical (e.g. AndroGel (testosterone gel)) vs transdermal (e.g. Androderm (transdermal testosterone patch))?

Topical vs Transdermal Testosterone Replacement Therapy

Topical testosterone gel is preferred over transdermal testosterone patches due to significantly better patient adherence, fewer skin reactions, and comparable efficacy in achieving therapeutic testosterone levels. 1

Comparison of Administration Routes

Topical Testosterone Gels

• Skin reactions: Only 5% of users experience erythema or pruritus 1
• Patient preference: 71% of patients prefer topical gel over patches or injections due to convenience, ease of use, and non-staining properties 1
• Application sites: Best absorption when applied to arms/shoulders; chest/abdomen and legs are acceptable alternatives but may result in lower testosterone levels 2
• Pharmacokinetics: Reaches steady-state in first 24 hours and maintains stable levels throughout application period 3

Transdermal Testosterone Patches

• Skin reactions: Up to 66% of users experience erythema or pruritus 1
• Cost: Higher annual cost ($2135.32) compared to intramuscular formulations ($156.24) according to 2016 Medicare Part D data 1
• Pharmacokinetics: Similar to gels in maintaining steady testosterone levels 3

Clinical Efficacy and Safety

Both topical and transdermal testosterone formulations:

• Effectively restore testosterone to mid-normal physiological levels (450-600 ng/dL) 4
• Improve sexual function, libido, quality of life, and body composition 4
• Show no consistent differences in long-term harms between transdermal formulations 1
• Carry lower risk of erythrocytosis compared to injectable testosterone 4

Monitoring Recommendations

For both formulations, follow these monitoring protocols:

1. Baseline assessment:

   • PSA measurement
   • Hematocrit/hemoglobin levels
   • Digital rectal examination
   • Assessment of voiding symptoms 1

2. Follow-up schedule:

   • First follow-up: 1-2 months after initiation
   • Subsequent visits: Every 3-6 months during first year
   • Annual follow-up once stable 1, 4

3. Monitoring parameters:

   • Testosterone levels
   • Hematocrit/hemoglobin (risk of polycythemia)
   • PSA (prostate health)
   • Cardiovascular risk factors 1, 4

Important Considerations and Precautions

• Secondary exposure: Topical gels carry risk of interpersonal transfer; patients should be counseled on proper application and precautions 3, 5
• Contraindications: Prostate cancer, male breast cancer, desire for fertility, severe sleep apnea, uncontrolled heart failure, hematocrit >54% 4
• Application technique: For gels, proper application technique is crucial for optimal absorption; some formulations come with applicators to prevent hand contact 5

Clinical Decision Algorithm

1. First-line: Topical testosterone gel applied to arms/shoulders

   • Better tolerated with fewer skin reactions
   • Higher patient adherence
   • Comparable efficacy to patches

2. Consider patches if:

   • Patient has difficulty with gel application
   • Concerns about secondary transfer of gel
   • Need for visible confirmation of application

3. Consider alternative routes (injectable) if:

   • Cost is a significant barrier
   • Patient preference after discussion of risks/benefits
   • Poor response to transdermal formulations

Common Pitfalls to Avoid

• Failing to counsel patients about secondary transfer risk with gels
• Not monitoring for skin reactions, especially with patches
• Overlooking the importance of application site for optimal absorption with gels
• Inadequate monitoring of hematocrit, PSA, and cardiovascular parameters
• Using testosterone for "age-related hypogonadism" without clear structural or genetic etiology 4