What is the best way to initiate Depot testosterone therapy in a male?

Initiating Depot Testosterone Therapy in Males

For depot testosterone initiation, start with testosterone enanthate or cypionate 100-200 mg intramuscularly every 2 weeks, or testosterone undecanoate 750 mg at initiation, at 4 weeks, then every 10 weeks thereafter. 1, 2

Pre-Treatment Requirements

Before initiating depot testosterone therapy, confirm hypogonadism diagnosis by:

• Measuring fasting morning total testosterone on at least 2 separate occasions 3
• Ensuring both measurements are below the normal range for adult males 3, 1
• Documenting clinical symptoms attributable to testosterone deficiency (low libido, erectile dysfunction, decreased energy, depressed mood, loss of muscle mass) 4, 5

Depot Formulation Selection and Dosing

Testosterone Enanthate or Cypionate (Short-Acting Depot)

The most effective and practical regimen is 200 mg intramuscularly every 2 weeks, which suppresses elevated LH to normal range and maintains serum testosterone within physiologic levels between doses 2. Alternative dosing of 100 mg weekly provides more stable levels but requires more frequent administration 2.

• Inject deeply into the gluteal muscle following standard precautions for oily solutions 1
• Measure testosterone levels at 2-3 months after initiation to confirm mid-normal range (500-600 ng/dL) 3
• For patients on every-2-week dosing, measure testosterone midway between injections targeting 500-600 ng/dL 3

Testosterone Undecanoate (Long-Acting Depot)

Dose: 750 mg (3 mL) intramuscularly at initiation, at 4 weeks, then every 10 weeks thereafter 1. This formulation provides stable testosterone levels with minimal fluctuations and requires only quarterly injections after the loading phase 5.

• Observe patients for 30 minutes post-injection in the healthcare setting due to risk of pulmonary oil microembolism (POME) reactions or anaphylaxis 1
• Inject deeply into the gluteal muscle only 1

Alternative: Subcutaneous Administration

Emerging evidence supports subcutaneous injection as an effective alternative to intramuscular administration:

• Start with 50-75 mg subcutaneous testosterone enanthate or cypionate weekly 6, 7
• Achieves serum testosterone within normal male range in all patients with doses of 50-150 mg weekly 6
• Patients overwhelmingly prefer subcutaneous over intramuscular (20 of 22 patients showed marked preference) 6
• Virtually painless with minimal injection site reactions (>95% reported no pain) 7
• Adjust dose at 6-7 weeks based on trough testosterone levels 7

Initial Monitoring Protocol

First follow-up at 1-2 months to assess both efficacy and safety 4:

• Measure hemoglobin/hematocrit (increases occur within 3 months; dose reduction required if hematocrit >54%) 4
• Assess for cardiovascular symptoms (chest pain, shortness of breath, dizziness) given incompletely defined cardiovascular safety profile 4
• Evaluate symptom improvement in sexual function, energy, and mood 4

Subsequent monitoring every 6-12 months once stable therapeutic levels confirmed 3

Setting Realistic Expectations

Counsel patients that testosterone therapy provides:

• Sexual function improvements within first few months of achieving therapeutic levels 4
• Small to modest improvements in mood and quality of life, not dramatic transformations 4
• Hemoglobin normalization within 3 months 4
• Gradual physical changes (increased muscle mass) over months 4

The goal is normalization of testosterone to mid-normal range combined with symptom improvement, not supraphysiologic levels 4. Emphasize concurrent lifestyle modifications including weight loss and increased physical activity, as these independently improve testosterone levels and symptoms 4.

Common Pitfalls to Avoid

• Do not use oral testosterone preparations in men without structural or genetic causes of hypogonadism 3
• Avoid testosterone undecanoate if unable to observe patient for 30 minutes post-injection due to POME risk 1
• Do not initiate therapy based on single testosterone measurement 3
• Recognize that testosterone is not effective monotherapy for erectile dysfunction; if ED is the primary concern, counsel regarding need for additional ED therapies (PDE5 inhibitors) 3