What is the recommended treatment for hypogonadism using testosterone therapy?

Testosterone Replacement Therapy for Hypogonadism

Testosterone replacement therapy is indicated for men with primary or secondary hypogonadism caused by disorders of the hypothalamus, pituitary gland, or testes, with transdermal preparations being the most effective first-line treatment option due to their stable serum levels and patient convenience. 1, 2, 3

Diagnosis and Confirmation

• Hypogonadism diagnosis requires:
  • Morning total testosterone concentration <300 ng/dL
  • At least two separate low testosterone measurements
  • Presence of clinical symptoms (decreased libido, erectile dysfunction, reduced energy)
  • Measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine primary vs. secondary hypogonadism 1

Treatment Options

First-Line: Transdermal Preparations

• Testosterone gels (1-2%): Applied daily to skin, providing stable testosterone levels
  • Advantages: Convenient application, stable serum levels, fewer side effects
  • Disadvantages: Risk of transfer to others, skin irritation in some patients
  • Dosing: 50-100 mg gel applied once daily 1, 4

Alternative Options

• Intramuscular injections:

  • Testosterone cypionate/enanthate: Every 1-2 weeks
    • Advantages: Lower cost, less frequent administration
    • Disadvantages: "Roller coaster" effect with fluctuating levels, injection site pain 1, 5
  • Testosterone undecanoate: Every 10-14 weeks
    • Advantages: More stable levels, fewer injections
    • Disadvantages: Higher cost 5

• Other formulations:

  • Buccal, subdermal, and nasal preparations are available but less commonly used 6

Monitoring Protocol

• Initial testosterone level testing: 2-3 months after treatment initiation or dose change
• Once stable: Every 6-12 months
• Additional monitoring:
  • Hematocrit: Before treatment, at 3-6 months, then annually
  • Prostate: Digital rectal exam and PSA before treatment, at 3-6 months, then according to guidelines for prostate cancer screening
  • Bone density: In men with history of fracture or risk factors for osteoporosis 1

Contraindications and Precautions

• Absolute contraindications:

  • Prostate cancer (theoretical risk, though recent evidence suggests possible use in select cases)
  • Male breast cancer
  • Desire for fertility in the near future (suppresses spermatogenesis) 1, 6

• Relative contraindications:

  • Severe obstructive sleep apnea
  • Severe lower urinary tract symptoms
  • Uncontrolled congestive heart failure
  • Hematocrit >54%
  • Untreated severe obstructive sleep apnea 1

Expected Benefits

• Improved sexual function and libido (strongest evidence)
• Enhanced quality of life
• Increased lean body mass
• Reduced abdominal subcutaneous adipose tissue
• Improved insulin sensitivity in men with metabolic syndrome
• Reduced inflammatory markers
• Small improvements in depressive symptoms 7, 1

Common Pitfalls and Caveats

1. Fertility concerns: Testosterone therapy suppresses the hypothalamic-pituitary-gonadal axis and can impair fertility. For men desiring fertility, consider alternative treatments like gonadotropins 6, 8

2. Cardiovascular risk: Evidence is mixed regarding cardiovascular risk. Careful monitoring is essential, particularly in men with pre-existing cardiovascular disease 7

3. Prostate monitoring: While no large-scale studies have confirmed increased risk of prostate cancer, regular monitoring is still recommended 1

4. Overtreatment: Supraphysiologic levels can cause erythrocytosis, sleep apnea, and other adverse effects. Proper dosing and monitoring are essential 7, 1

5. Inappropriate use: Many men receive testosterone without proper testing or for non-specific symptoms of aging alone, which is not recommended 7

Treatment Algorithm

1. Confirm diagnosis with two morning testosterone measurements <300 ng/dL plus symptoms
2. Rule out reversible causes (obesity, medications, chronic illness)
3. Select treatment:
   • For most patients: Start with transdermal gel (50-100 mg daily)
   • For cost-sensitive patients: Consider intramuscular injections
   • For fertility preservation: Consider alternative treatments (gonadotropins)
4. Monitor response at 2-3 months:
   • If inadequate symptom improvement and levels remain low: Increase dose
   • If excessive levels or side effects: Decrease dose
5. Long-term monitoring every 6-12 months for testosterone levels, hematocrit, and prostate health

Testosterone therapy in hypogonadism provides significant benefits for sexual function and quality of life, though benefits for other symptoms of aging may be limited. Careful patient selection, appropriate formulation choice, and regular monitoring are essential for optimizing outcomes while minimizing risks 7, 1.