What are the recommendations for testosterone therapy in men with normal range but low normal bioavailability testosterone?

Testosterone Therapy for Men with Low-Normal Bioavailable Testosterone

Testosterone therapy is not recommended for men with testosterone levels within the normal range, even if bioavailable testosterone is in the low-normal range, unless they have consistent symptoms of testosterone deficiency. 1

Diagnostic Criteria and Assessment

• Testosterone deficiency should only be diagnosed in men who have:
  • Consistent symptoms and signs of androgen deficiency
  • Unequivocally low serum testosterone levels 1, 2
• Initial testing should include:
  • Morning total testosterone measurement (most reliable time)
  • Confirmation with a repeat morning total testosterone test
  • In cases of borderline total testosterone or suspected SHBG abnormalities, measurement of free or bioavailable testosterone using validated assays 2, 3

Clinical Decision Making for Low-Normal Bioavailable Testosterone

For men with normal total testosterone but low-normal bioavailable testosterone:

1. Evaluate for symptoms of testosterone deficiency:

   • Sexual dysfunction (erectile dysfunction, decreased libido)
   • Fatigue or decreased energy
   • Reduced muscle mass and strength
   • Depressed mood
   • Decreased bone mineral density

2. Consider alternative causes of symptoms:

   • Obesity
   • Diabetes
   • Metabolic syndrome
   • Sleep disorders
   • Depression
   • Medication side effects

3. Address modifiable factors first:

   • Weight loss for overweight/obese patients
   • Increased physical activity
   • Improved sleep hygiene
   • Management of comorbid conditions 1

Important Considerations and Pitfalls

• Common pitfall: Treating laboratory values rather than patients. Normal-range testosterone with low-normal bioavailable testosterone alone is not an indication for testosterone therapy without corresponding symptoms.

• Cardiovascular considerations:

  • Assess all patients for ASCVD risk factors before considering therapy
  • Testosterone therapy should not be initiated within 3-6 months of a cardiovascular event
  • Monitor hematocrit regularly (discontinue if >54%) 1

• Fertility considerations:

  • Exogenous testosterone suppresses spermatogenesis
  • Consider alternative approaches for men wishing to preserve fertility 1

• Contraindications to testosterone therapy:

  • Prostate or breast cancer
  • Hematocrit >50%
  • Severe untreated sleep apnea
  • Uncontrolled heart failure
  • PSA >4.0 ng/mL or >3.0 ng/mL in high-risk men 1, 2

Monitoring Parameters if Therapy is Initiated

If therapy is deemed appropriate after thorough evaluation:

• Target total testosterone: 450-600 ng/dL (mid-normal range)
• Check testosterone levels 2-3 months after starting therapy
• Regular monitoring every 6-12 months
• Monitor hematocrit, PSA (in men >40), and symptoms 1

Evidence Quality and Consensus

The American Urological Association, Endocrine Society, and American College of Physicians all agree that testosterone therapy should be reserved for men with both symptoms of testosterone deficiency and confirmed low testosterone levels 1, 2, 3. The evidence does not support treating men with normal-range testosterone values, even if bioavailable testosterone is in the low-normal range.

Current guidelines emphasize addressing underlying comorbidities that may affect testosterone bioavailability rather than supplementing testosterone in men with normal total testosterone levels 1, 4.