What is the initial treatment for symptomatic low testosterone?

Initial Treatment for Symptomatic Low Testosterone

Testosterone replacement therapy (TRT) is the initial treatment for men with confirmed symptomatic low testosterone, defined as total testosterone levels below 300 ng/dL on two separate morning measurements along with clinical symptoms. 1

Diagnosis Confirmation

Before initiating treatment, ensure proper diagnosis:

• Confirm low testosterone with two separate morning measurements below 300 ng/dL 1
• Document presence of symptoms (reduced energy, fatigue, decreased libido, erectile dysfunction, etc.) 1
• Measure luteinizing hormone (LH) levels to determine etiology (primary vs. secondary hypogonadism) 1
• Rule out contraindications to therapy

Treatment Options

First-Line: Testosterone Replacement Therapy

The American Urological Association recommends TRT as first-line treatment for symptomatic hypogonadism. Available formulations include:

1. Topical gels/solutions (preferred initial option for older men) 2

   • Applied daily to shoulders and upper arms
   • Target testosterone levels: 450-600 ng/dL (mid-normal range)
   • Advantages: Steady hormone levels, ease of application
   • Disadvantages: Risk of transfer to women/children, skin irritation

2. Intramuscular injections

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

3. Other formulations

   • Buccal, nasal, subdermal pellets
   • Consider based on patient preference and cost considerations

Special Considerations

For men desiring fertility preservation:

• Consider alternative approaches that stimulate endogenous testosterone production 2, 3:
  • Selective estrogen receptor modulators (SERMs)
  • Gonadotropins
  • Aromatase inhibitors

Monitoring Protocol

After initiating TRT:

• Check testosterone levels 4-6 weeks after starting treatment 2

• Follow-up visits at 1-2 months after initiation 2

• Monitor for adverse effects:

  • Erythrocytosis (dose-dependent: 2.8-17.9%) 2
  • PSA elevation (most common adverse reaction: 11.1%) 4
  • Emotional lability (2.6%) 4
  • Hypertension (2.1%) 4
  • Elevated hematocrit/hemoglobin (2.1%) 4

• Adjust dosage based on serum levels and symptom response:

  • If testosterone >750 ng/dL: Decrease dose
  • If testosterone 350-750 ng/dL: No change
  • If testosterone <350 ng/dL: Increase dose 2

Contraindications

TRT is contraindicated in men 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) 2

Common Pitfalls to Avoid

• Diagnosing hypogonadism based on a single testosterone measurement
• Failing to measure free testosterone in obese patients
• Overlooking secondary causes of hypogonadism
• Initiating therapy without proper baseline evaluation
• Not monitoring for adverse effects, particularly hematocrit elevation and blood pressure increases
• Using testosterone for "age-related hypogonadism" without structural or genetic etiology 2

Patient Education

Patients should be informed about:

• The importance of long-term therapy
• Potential benefits (improved sexual function, quality of life)
• Potential risks (erythrocytosis, PSA elevation)
• Proper application techniques for topical preparations
• Risk of transfer to women and children (for topical preparations)
• Need for regular monitoring

TRT offers small but significant improvements in sexual function (moderate-certainty evidence) and quality of life (low-to-moderate certainty evidence), with little to no effect on physical functioning, energy/vitality, or cognition 2.