What are the guidelines for initiating subcutaneous testosterone (testosterone) therapy?

Guidelines for Initiating Subcutaneous Testosterone Therapy

Subcutaneous testosterone administration is a viable alternative to intramuscular injections, providing comparable testosterone levels with less pain and greater ease of self-administration, making it an appropriate option for testosterone replacement therapy in hypogonadal men. 1

Diagnostic Criteria Before Initiating Therapy

• Confirm hypogonadism diagnosis with:
  • Morning total testosterone levels < 300 ng/dL on at least two separate occasions 2, 3, 4
  • Presence of symptoms associated with testosterone deficiency:
    • Sexual symptoms: reduced libido, erectile dysfunction, decreased spontaneous/morning erections 3
    • Physical symptoms: decreased energy, decreased physical strength/activity, fatigue 3
    • Psychological symptoms: low mood, decreased motivation, concentration difficulties 3

Pre-Treatment Evaluation

1. Laboratory assessment:

   • Morning total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) 3
   • Hemoglobin/hematocrit (withhold therapy if Hct > 50%) 2
   • PSA in men over 40 years (consider reflex testing if elevated) 2

2. Risk factor assessment:

   • Evaluate for ASCVD risk factors (both fixed and modifiable) 2
   • Screen for contraindications:
     • Absolute: prostate cancer, breast cancer, desire for near-term fertility, severe sleep apnea, uncontrolled heart failure, recent cardiovascular events 3
     • Relative: history of hepatocellular carcinoma, thrombosis, other cardiovascular risk factors 3

3. Fertility considerations:

   • Perform reproductive health evaluation if fertility is desired 2
   • Consider testicular exam and serum FSH measurement 2
   • Discuss that exogenous testosterone suppresses spermatogenesis 3

Dosing and Administration of Subcutaneous Testosterone

1. Subcutaneous testosterone cypionate/enanthate:

   • Initial dose similar to IM route (typically 50-200 mg every 1-2 weeks) 4, 1
   • Self-administered into subcutaneous tissue (easier than IM injections) 1, 5
   • Provides stable serum testosterone levels between injections 5

2. Subcutaneous testosterone pellets:

   • Dosing based on BMI:
     • BMI <25 kg/m²: 6-9 pellets
     • BMI ≥25 kg/m²: 10-12 pellets 6
   • Reimplantation typically needed every 100-120 days 6

3. Dose adjustments:

   • Adjust dose based on pre-dose morning testosterone levels:

     • 750 ng/dL: Decrease daily dose by 20-25%

     • 350-750 ng/dL: No change
     • <350 ng/dL: Increase daily dose by 20-25% 3

Monitoring Protocol

1. Testosterone levels:

   • Measure 2-4 weeks after starting therapy 3
   • For subcutaneous injections, levels remain stable between injections 5
   • Target mid-normal range (450-600 ng/dL) 3
   • Continue monitoring every 6-12 months 2

2. Safety monitoring:

   • Hemoglobin/hematocrit: Discontinue if Hct >54% 2
   • PSA: Follow standard AUA guidelines for prostate cancer screening 2
   • Consider discontinuation after 3-6 months if symptoms don't improve 3

Expected Benefits and Potential Risks

Benefits:

• Improvements in sexual function and libido 2
• Small improvements in quality of life 2
• Potential improvements in bone mineral density, lean body mass, and depressive symptoms 2
• Subcutaneous route offers:
  • Less pain than IM injections 1
  • Easier self-administration 1
  • Stable testosterone levels between injections 5

Risks:

• Erythrocytosis (dose-dependent: 2.8-17.9%) 3
• Suppression of spermatogenesis 3
• Potential for gynecomastia (uncommon) 2
• No consistent evidence of increased risk for cardiovascular events, prostate cancer, or venous thromboembolism 2

Special Considerations

• Fertility concerns: Exogenous testosterone should not be prescribed to men interested in current or future fertility; consider alternative treatments like hCG, SERMs, or aromatase inhibitors 3

• Estradiol monitoring: Men with elevated baseline estradiol should be referred to an endocrinologist; monitor for gynecomastia symptoms 2

• Patients with BMI ≥25 kg/m²: May attain lower testosterone peaks with slower decay rates compared to those with BMI <25 kg/m² 6

The subcutaneous route offers practical advantages over intramuscular administration while providing comparable efficacy and safety, making it an excellent option for many patients requiring testosterone replacement therapy.