What are the treatment options for hypogonadism (low sex hormone production) in males?

Treatment Options for Male Hypogonadism

For males with hypogonadism, the optimal treatment approach depends on the underlying cause, with testosterone replacement therapy (TRT) being the primary treatment for primary hypogonadism and human chorionic gonadotropin (HCG) therapy being an excellent option for secondary hypogonadism, particularly when fertility preservation is desired. 1

Diagnosis and Classification

Before initiating treatment, it's essential to:

• Confirm diagnosis with two morning testosterone measurements (between 8-10 AM) on separate days
• Determine the type of hypogonadism:
  • Primary hypogonadism: Low testosterone with elevated LH/FSH (testicular failure)
  • Secondary hypogonadism: Low testosterone with normal/low LH/FSH (pituitary-hypothalamic dysfunction)

Treatment Options by Type

Primary Hypogonadism Treatment

Testosterone replacement therapy (TRT) is the mainstay treatment for primary hypogonadism. Available formulations include:

1. Testosterone Gel (1.62%):

   • Starting dose: 40.5 mg applied topically once daily to shoulders and upper arms
   • Adjustable between 20.25-81 mg based on serum levels
   • Target testosterone level: 350-750 ng/dL 2
   • Advantages: Non-invasive, daily application maintains stable levels
   • Caution: Risk of transfer to women and children through skin contact

2. Injectable Testosterone:

   • Recommended regimens:
     • 100-200 mg every 2 weeks or 50 mg weekly intramuscularly 1
     • 200 mg every 2 weeks or 300 mg every 3 weeks are most effective regimens 3
   • Advantages: Less frequent administration, cost-effective
   • Disadvantages: Fluctuating testosterone levels

3. Other Formulations:

   • Transdermal patches
   • Buccal tablets
   • Subcutaneous pellets

Secondary Hypogonadism Treatment

1. Human Chorionic Gonadotropin (HCG):

   • Dosage: 500-2500 IU, 2-3 times weekly via intramuscular injection 1
   • Alternative regimen: 500-1000 IU three times weekly for 3 weeks, then twice weekly for 3 weeks 4
   • Key advantage: Stimulates endogenous testosterone production without suppressing spermatogenesis, preserving fertility 1
   • Best for: Younger patients desiring fertility preservation
   • Response correlates with pre-treatment testicular size

2. Combined Therapy:

   • If HCG alone is insufficient, consider adding FSH therapy after testosterone levels normalize 1
   • For persistent infertility despite medical therapy, consider referral for assisted reproductive technologies

Monitoring and Follow-up

• Initial follow-up: 1-2 months after starting treatment
• Testosterone levels: Check at 2-3 months after initiation or dose changes, then every 6-12 months once stable
• Hemoglobin/hematocrit: Monitor regularly to detect polycythemia
• Prostate: PSA and digital rectal examinations to detect potential prostate cancer
• Dose adjustments based on pre-dose morning testosterone:

  Pre-Dose Morning Testosterone	Dose Adjustment
  >750 ng/dL	Decrease daily dose by 20-25%
  350-750 ng/dL	No change
  <350 ng/dL	Increase daily dose by 20-25%

Potential Side Effects and Contraindications

Side Effects of TRT

• Erythrocytosis (2.8-17.9%, dose-dependent)
• Suppression of spermatogenesis
• Peripheral edema
• Emotional lability
• Local injection site reactions (injectable forms)
• Secondary exposure risk (gel formulations)

Absolute Contraindications for TRT

• Prostate cancer
• Breast cancer
• Desire for near-term fertility
• Severe sleep apnea
• Uncontrolled heart failure
• Recent cardiovascular events

Special Considerations

1. Fertility Concerns:

   • For men desiring fertility, HCG is preferred over TRT 1
   • TRT significantly suppresses spermatogenesis

2. Lifestyle Modifications:

   • Weight loss through diet and physical activity can improve testosterone levels in obesity-associated secondary hypogonadism
   • Should be recommended as first-line or adjunctive therapy

3. Age-Related Hypogonadism:

   • Safety and efficacy of testosterone gel 1.62% in "age-related hypogonadism" have not been established 2
   • Careful risk-benefit assessment needed in older men

4. Cardiovascular Risk:

   • High-quality evidence suggests TRT does not increase stroke or heart attack risk in men 45-80 years old 1
   • Regular cardiovascular assessment is necessary, particularly in elderly patients

By following this structured approach to treatment selection and monitoring, clinicians can effectively manage male hypogonadism while minimizing risks and optimizing outcomes for their patients.