What is the recommended dosage and administration of Depotestosteron (testosterone enanthate or cypionate) for testosterone replacement therapy?

Dosage and Administration of Testosterone Enanthate/Cypionate for Testosterone Replacement Therapy

For testosterone replacement therapy in hypogonadal males, the recommended dosage of testosterone enanthate or cypionate is 50-200 mg intramuscularly every 2 weeks, or 50 mg weekly, targeting mid-normal testosterone levels (500-600 ng/dL). 1, 2, 3

Dosage Options

Intramuscular Administration (First-line)

• Standard dosing: 50-200 mg every 2 weeks 1, 2
• Alternative dosing: 50 mg weekly (preferred for more stable levels) 3
• Maximum dose: 400 mg per month 1, 2
• Injection site: Deep gluteal muscle for administration by another person; thigh for self-injection 3

Monitoring and Dose Adjustment

• Test testosterone levels 2-3 months after initiation or dose change 3
• For IM injections, measure levels midway between injections 3
• Target mid-normal testosterone values (500-600 ng/dL) 3, 4
• Once stable levels are achieved, monitor every 6-12 months 3

Pharmacokinetic Considerations

Intramuscular Injections

• Testosterone levels fluctuate significantly with IM injections 3
• Peak levels occur 2-5 days after injection 3
• Return to baseline typically occurs 10-14 days after injection 3
• These fluctuations may contribute to increased cardiovascular risk compared to transdermal preparations 3

Dosing Frequency Considerations

• Weekly injections (50 mg) provide more stable testosterone levels than biweekly injections 5
• 200 mg every 2 weeks and 300 mg every 3 weeks were found to be effective regimens in terms of suppression of LH and frequency of administration 5

Safety Monitoring

Required Baseline Tests

• PSA and hematocrit/hemoglobin levels 3
• Digital rectal examination 3
• Lipid evaluation (optional) 3
• Assessment of voiding symptoms 3
• Screening for sleep apnea 3

Follow-up Monitoring

• First follow-up: 1-2 months after initiation 3
• Subsequent visits: Every 3-6 months for the first year, then yearly 3
• At each visit, assess:
  • Symptomatic response
  • Voiding symptoms
  • Sleep apnea
  • Digital rectal examination
  • Testosterone levels
  • PSA levels
  • Hematocrit/hemoglobin 3

Potential Adverse Effects

Common Side Effects

• Erythrocytosis (more common with injections than transdermal preparations) 3
  • 43.8% of patients on IM injections vs. 15.4% on transdermal patches had elevated hematocrit 3, 6
• Testicular atrophy and reduced fertility 3
• Fluid retention (uncommon and generally mild) 3
• Local injection site reactions (pain, soreness, bruising) 3

Serious Concerns

• FDA has required labeling changes regarding potential increased risk of heart attack and stroke 3
• Injections may be associated with greater cardiovascular risk compared to gels due to fluctuating testosterone levels 3
• If hematocrit rises above normal range, consider temporarily withholding therapy, reducing dosage, or performing phlebotomy 3

Alternative Administration Routes

If IM injections are not preferred or tolerated:

• Subcutaneous administration: Emerging evidence supports 50-100 mg weekly as an effective and less painful alternative 7, 8, 9
• Transdermal preparations: Provide more stable hormone levels with less risk of erythrocytosis 3, 6

Clinical Pearls

• Testosterone enanthate and cypionate are interchangeable at equivalent doses 3, 1, 2
• Warming and shaking the vial can redissolve any crystals that may form during storage 1
• Avoid intravascular injection by using proper IM injection technique 2
• Injections more frequently than every two weeks are rarely indicated unless using lower weekly doses 2