What is the recommended treatment regimen for hypogonadism using testosterone gel (Testosterone Replacement Therapy - TRT)?

Testosterone Gel Treatment Regimen for Hypogonadism

For hypogonadal men, the recommended testosterone gel treatment regimen starts with 40.5 mg of testosterone (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning to the shoulders and upper arms, with dose adjustments based on serum testosterone levels measured at 14 and 28 days after initiation. 1

Diagnosis Confirmation

• Prior to initiating testosterone gel therapy, confirm hypogonadism diagnosis by ensuring serum testosterone concentrations have been measured in the morning on at least two separate days and are below the normal range 1, 2
• Consider addressing modifiable factors that may contribute to hypogonadism, such as obesity, metabolic disorders, and medications that interfere with the hypothalamic-pituitary axis 2

Initial Dosing and Administration

• Start with 40.5 mg of testosterone gel 1.62% applied once daily in the morning to clean, dry, intact skin of the upper arms and shoulders 1
• Apply using the palm of the hand and spread across the maximum surface area as directed in product instructions 1
• Arms/shoulders application site provides optimal absorption compared to other body sites 3
• Do not apply to abdomen, genitals, chest, armpits, or knees 1

Dose Titration Protocol

• Adjust dose based on pre-dose morning serum testosterone concentration at approximately 14 days and 28 days after starting treatment 1
• Follow these titration guidelines:
  • If testosterone > 750 ng/dL: Decrease daily dose by 20.25 mg
  • If testosterone 350-750 ng/dL: No change, continue current dose
  • If testosterone < 350 ng/dL: Increase daily dose by 20.25 mg 1
• Dose can be adjusted between minimum of 20.25 mg and maximum of 81 mg of testosterone 1

Monitoring Schedule

• Test testosterone levels 2-3 months after treatment initiation and/or after any dose change 4
• Once stable levels are confirmed, monitor every 6-12 months 4
• For patients receiving transdermal preparations, levels can be measured at any time, with understanding that peak values occur 6-8 hours after application 4

Safety Considerations

• Testosterone gel is contraindicated in men seeking fertility - use gonadotropin therapy instead for secondary hypogonadism 2
• Active or treated male breast cancer remains an absolute contraindication for testosterone therapy 2
• Testosterone therapy is generally safe and does not worsen lower urinary tract symptoms (LUTS) or prostate volume significantly except in men with severe symptoms 2
• Recent evidence from the TRAVERSE trial confirmed no difference in prostate cancer incidence between testosterone and placebo groups 2
• Testosterone therapy does not appear to worsen obstructive sleep apnea 2
• No increased risk for mortality, cardiovascular events, prostate cancer, or venous thromboembolism has been observed in observational studies 2

Important Precautions

• Avoid fire, flames, or smoking until gel has dried (alcohol-based products are flammable) 1
• Avoid swimming, showering, or washing application site for minimum of 2 hours after application 1
• Be aware of potential secondary exposure to women and children - cover application site with clothing once dry and wash hands thoroughly with soap and water after application 1
• Monitor for potential side effects including polycythemia (withdraw treatment and consider phlebotomy if hematocrit >54%) and significant PSA increases 2

Formulation Considerations

• Transdermal testosterone preparations (gels and patches) provide more stable day-to-day testosterone levels compared to injections 4
• Patient preference may vary - some prefer gels for convenience and ease of use, while others choose injections due to lower cost 2, 4
• Annual cost differences are significant: $2,135.32 for transdermal formulations versus $156.24 for intramuscular formulations (2016 Medicare data) 2, 4

Expected Benefits

• Sexual function and mood typically improve maximally by day 30 of treatment 5
• Muscle strength increases are generally observed by 90 days of treatment 5
• Lean body mass increases and fat mass decreases correlate with achieved serum testosterone levels 5
• Testosterone gel treatment has been shown to improve vitality, fatigue, and depressive symptoms 2