What is the best topical testosterone (testosterone replacement therapy)?

Best Topical Testosterone for Testosterone Replacement Therapy

For testosterone replacement therapy, transdermal testosterone gel 1.62% (such as Testim or AndroGel) applied to the upper arms and shoulders is the preferred topical formulation, offering superior efficacy, more stable testosterone levels, and better tolerability compared to patches or other concentrations. 1, 2

Recommended Formulation and Dosing

First-Line Topical Option: 1.62% Testosterone Gel

• Start with 40.5 mg (approximately 2 pumps or one 40.5 mg packet) applied daily to upper arms and shoulders 1, 2
• The 1.62% gel formulation achieves eugonadal testosterone levels in 81.6-82.5% of hypogonadal men, significantly superior to placebo 3
• This concentration provides increased skin permeation and requires reduced application volume compared to 1% formulations 3, 4

Application Site Matters

• Upper arms and shoulders are the optimal application sites, achieving the highest testosterone levels compared to chest/abdomen or legs 5
• Application to arms/shoulders produces significantly better absorption than other anatomical sites (A > C ≥ L, P = 0.011) 5
• The FDA-approved application sites for 1.62% gel are specifically the upper arms and shoulders 2

Alternative Topical Formulations

1% Testosterone Gel (AndroGel 1%)

• Dose: 50-100 mg daily 1
• Less efficient than 1.62% formulation but still effective 3
• Requires larger application volume 4

Testosterone Patches (Androderm)

• Dose: 2-6 mg per 24 hours 1
• Achieve similar testosterone normalization as gels 6
• Major limitation: significantly worse skin tolerability with frequent application-site reactions 6, 7
• Should be avoided as first-line due to poor tolerability profile 6

2.5% Hydroalcoholic Gel (Testavan/TGW)

• Can be applied to scrotal skin (1 g daily) or non-scrotal skin (5 g daily) 6
• Removed by washing 10 minutes after application, reducing transfer risk 6
• Non-scrotal application showed superior testosterone levels compared to patches 6
• Not as widely available as 1.62% formulations 4

Critical Monitoring Protocol

Initial Monitoring

• Measure testosterone levels 2-3 months after starting therapy or any dose change 1, 8
• Target mid-normal testosterone values (450-600 ng/dL or 500-600 ng/dL) 1, 8
• For gel formulations, testosterone can be measured at any time, though peak occurs 6-8 hours post-application 8

Ongoing Monitoring

• Once stable levels achieved, monitor every 6-12 months 1, 8
• Check hemoglobin/hematocrit for erythrocytosis 8
• Monitor PSA and perform digital rectal examination 7

Dose Titration Strategy

If initial 40.5 mg dose inadequate:

• Increase to 60.75 mg (3 pumps: 2 to one arm/shoulder, 1 to opposite side) 2
• Maximum dose: 81 mg (4 pumps: 2 to each arm/shoulder) 2
• Dose adjustments should be made at days 14,28, and 42 based on testosterone levels 3

If testosterone levels remain low despite maximum gel dose:

• Consider switching to injectable testosterone (enanthate/cypionate 50-100 mg weekly) for more reliable absorption 1

Key Safety Considerations

Transfer Risk Prevention

• Allow application site to dry completely before dressing 2
• Avoid showering, swimming, or bathing for at least 2 hours after application 2
• Wash hands immediately with soap and water after application 2
• Cover application site with clothing to prevent transfer to partners or children 8
• Women and children are at highest risk for virilization and precocious puberty from secondary exposure 8

Cardiovascular Considerations

• Transdermal preparations may have lower cardiovascular risk compared to injectable testosterone 8, 1
• Injectable formulations show greater risk of cardiovascular events, possibly due to fluctuating testosterone levels 8, 1
• Assess cardiovascular risk factors before initiating therapy 8

Common Pitfalls to Avoid

• Do NOT use topical testosterone for lichen sclerosus - it is inferior to clobetasol propionate and no better than emollient 8
• Do NOT prescribe alkylated oral testosterone due to hepatotoxicity 8
• Do NOT use compounded testosterone when FDA-approved products are available - compounded preparations have variable potency and quality 8
• Do NOT continue therapy if target testosterone levels achieved but symptoms don't improve after 3-6 months 8
• Do NOT apply gel to genital areas - approved sites are upper arms/shoulders only 2

Why Gels Over Patches

Gels are strongly preferred over patches because:

• Similar efficacy in achieving eugonadal testosterone levels 6
• Significantly better tolerability with fewer application-site reactions 6, 7
• More convenient daily application 8
• Better patient satisfaction (71% prefer gel over patches) 8

Cost Considerations

• Transdermal formulations cost significantly more than injectable testosterone (annual cost $2,135 vs $156 for intramuscular) 8
• However, the convenience, stable levels, and reduced cardiovascular risk may justify the higher cost for appropriate patients 8, 1
• If cost is prohibitive, weekly injectable testosterone (50-100 mg) provides more stable levels than biweekly dosing and is more affordable 1