What is the initial treatment for symptomatic low testosterone?

Initial Treatment for Symptomatic Low Testosterone

For patients with confirmed symptomatic hypogonadism, testosterone replacement therapy (TRT) is the recommended first-line treatment when fertility is not a concern, while human chorionic gonadotropin (hCG) injections are preferred when fertility preservation is desired. 1

Diagnosis Confirmation

Before initiating treatment, ensure proper diagnosis with:

• Two separate morning testosterone measurements below 300 ng/dL
• Documented symptoms of hypogonadism
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to determine primary vs. secondary hypogonadism
• Rule out contraindications to therapy

Treatment Options Based on Fertility Concerns

When Fertility Is Not a Concern:

1. Topical Testosterone Preparations (First-Line)

   • Preferred initial option, especially for older men 1
   • Advantages: Steady hormone levels, ease of application
   • Disadvantages: Risk of transfer to women/children, skin irritation, higher cost
   • Application: Apply to shoulders and upper arms that will be covered by a short-sleeve shirt 2
   • Important safety measures:
     • Wash hands immediately after application
     • Cover application area with clothing after gel dries
     • Avoid skin-to-skin contact with others 2

2. Intramuscular Injections

   • Testosterone cypionate or enanthate every 1-2 weeks
   • Advantages: Lower cost, less frequent administration
   • Disadvantages: Fluctuating hormone levels, injection discomfort 1

When Fertility Preservation Is Desired:

• hCG Injections (First-Line)
  • Dosage: 500-2500 IU, 2-3 times weekly
  • Option to add FSH injections after testosterone levels normalize if needed
  • Continue for 12-24 months for optimal results 1
  • Important: Exogenous testosterone suppresses spermatogenesis and can cause oligospermia or azoospermia 1

Monitoring and Follow-up

• Check testosterone levels 4-6 weeks after treatment initiation

• Schedule follow-up visits 1-2 months after initiation

• Continue monitoring every 3-6 months thereafter

• Target testosterone levels: 450-600 ng/dL (mid-normal range) 1

• Monitor for adverse effects:

  • Erythrocytosis (dose-dependent: 2.8-17.9%)
  • Prostate issues (PSA elevation)
  • Blood pressure increases
  • Peripheral edema
  • Emotional lability 1, 2

Dose Adjustments

Adjust dose based on serum levels and symptom response:

• If pre-dose morning testosterone >750 ng/dL: Decrease daily dose by 20-25 mg
• If 350-750 ng/dL: No change
• If <350 ng/dL: Increase daily dose by 20-25 mg 1

Contraindications

TRT is contraindicated in patients with:

• Prostate cancer
• Male breast cancer
• Desire for fertility in the near future
• Severe obstructive sleep apnea
• Uncontrolled congestive heart failure
• Hematocrit >54%
• Active alcohol use disorder (particularly for oral alkylated testosterone) 1

Common Adverse Effects

• Erythrocytosis (dose-dependent)
• Suppression of spermatogenesis
• Peripheral edema
• Emotional lability
• Potential cardiovascular effects (long-term safety uncertain) 1, 2

Patient Education

Patients should be informed about:

• The importance of long-term therapy
• Potential benefits and risks
• Proper application techniques for topical preparations
• Risk of transfer to women and children
• Need for regular monitoring 1

Lifestyle Optimization

While initiating TRT, also recommend:

• Physical activity and diet optimization
• Weight loss programs for reducing belly fat
• Optimizing glycemic control if diabetic 1

TRT has shown small but significant improvements in sexual function (moderate-certainty evidence) and quality of life (low-to-moderate certainty evidence), but little to no effect on physical functioning, energy/vitality, or cognition 1.