What is the recommended initial dose and treatment regimen for a patient starting testosterone replacement therapy (TRT)?

Starting Testosterone Replacement Therapy

Recommended Initial Dosing

For patients starting testosterone replacement therapy, begin with topical testosterone gel 1.62% at 40.5 mg (2 pump actuations) applied once daily to the shoulders and upper arms, or alternatively, intramuscular testosterone enanthate 100 mg weekly or 100-200 mg every 2 weeks. 1, 2, 3

Topical Testosterone (Preferred for Most Patients)

• Start with testosterone gel 1.62% at 40.5 mg (2 pump actuations or one 40.5 mg packet) applied once daily in the morning to clean, dry skin of the shoulders and upper arms 3
• Alternative topical options include 1% testosterone gel at 50 mg (one 5-g packet) once daily or testosterone patches at 4 mg/day (two 2-mg patches) 2
• Topical preparations provide more stable day-to-day testosterone levels and may be preferable for patients with cardiovascular risk factors, as they avoid the supraphysiologic and subtherapeutic fluctuations seen with injections 2
• The application site must be covered with clothing once dry, and patients should avoid swimming or washing the site for at least 2 hours after application 3

Injectable Testosterone

• Testosterone enanthate or cypionate: 100 mg weekly or 100-200 mg every 2 weeks intramuscularly 1, 4
• Subcutaneous administration at 50-150 mg weekly (median 75-80 mg) is an effective and well-accepted alternative to intramuscular injection, with all patients preferring subcutaneous over intramuscular delivery 5
• Injectable testosterone may carry greater cardiovascular risk compared to transdermal preparations due to fluctuating levels 1, 2

Dose Titration Protocol

Measure testosterone levels at 2-3 months after initiation, then adjust dose to achieve mid-normal range (450-600 ng/dL): 1, 2

• For topical gel, testosterone can be measured at any time after steady state is reached 2
• For injectable testosterone, measure levels midway between injections 1, 2
• Adjust topical gel dose between 20.25 mg (1 pump) minimum and 81 mg (4 pumps) maximum based on pre-dose morning testosterone levels: 3
  • If testosterone >750 ng/dL: decrease by 20.25 mg
  • If testosterone 350-750 ng/dL: continue current dose
  • If testosterone <350 ng/dL: increase by 20.25 mg
• Once stable levels achieved, monitor every 6-12 months 6, 1, 2

Critical Safety Considerations Before Initiating

Do not start testosterone therapy in the following situations:

• Within 3-6 months of a cardiovascular event (myocardial infarction, stroke) 6, 2
• In men currently trying to conceive, as exogenous testosterone suppresses spermatogenesis 6, 2
• Never prescribe alkylated oral testosterone due to hepatotoxicity risk 2

Monitoring Requirements

Essential monitoring parameters include:

• Hematocrit/hemoglobin: testosterone stimulates erythropoiesis, and elevation above normal range can increase blood viscosity and aggravate vascular disease, particularly in elderly patients 6
• Erythrocytosis occurs more frequently with injectable testosterone (43.8%) compared to topical preparations (2.8-17.9%) 2
• Cardiovascular risk assessment is mandatory, especially in elderly or obese patients who should receive concurrent weight loss counseling 2

Special Populations

For patients desiring fertility preservation:

• Use aromatase inhibitors, human chorionic gonadotropin (hCG), or selective estrogen receptor modulators instead of exogenous testosterone 6, 2
• Only hCG is FDA-approved for use in males among these alternatives 6

Product Selection

• Prescribe commercially manufactured testosterone products rather than compounded preparations when possible, as compounded products lack FDA oversight and have considerable variation in potency and quality 6
• Topical testosterone products have different doses, strengths, and application instructions that result in different systemic exposure and are not interchangeable 3

Treatment Discontinuation

Discontinue testosterone therapy at 3-6 months if patients achieve target testosterone levels (450-600 ng/dL) but report no symptom improvement, as there is no utility in continuing therapy without clinical benefit 6