What is the recommended management for low testosterone (hypogonadism)?

Management of Low Testosterone (Hypogonadism)

Testosterone replacement therapy (TRT) should only be initiated for men with confirmed hypogonadism (consistently low testosterone levels <300 ng/dL measured in the morning on at least two separate days) who have specific symptoms of testosterone deficiency and want to improve sexual function. 1

Diagnostic Criteria

• Laboratory confirmation:

  • Total testosterone <300 ng/dL on at least two separate morning measurements 1, 2
  • Normal ranges: Total testosterone 300-950 ng/dL, Free testosterone 50-200 pg/mL 1

• Symptoms to evaluate:

  • Sexual dysfunction (primary indication for treatment)
  • Reduced energy, fatigue, depression
  • Poor concentration, irritability
  • Reduced sex drive, infertility 1

• Physical examination findings:

  • Body habitus, virilization status
  • Body mass index, gynecomastia
  • Testicular size, prostate size 1

Treatment Algorithm

1. Confirm diagnosis with two morning testosterone measurements <300 ng/dL plus symptoms 1, 2

2. Rule out contraindications:

   • Breast or prostate cancer
   • Hematocrit >50%
   • Severe untreated sleep apnea
   • Severe lower urinary tract symptoms
   • Uncontrolled heart failure
   • Current or future fertility desires 1

3. Initiate TRT (if indicated):

   • Starting dose: 40.5 mg testosterone gel (1.62%) applied topically once daily in the morning to shoulders and upper arms 2
   • Alternative formulations include intramuscular injections based on patient preference 3

4. Titrate dose based on:

   • Pre-dose morning serum testosterone at 14 and 28 days after starting treatment 2
   • Target total testosterone levels: 450-600 ng/dL (middle tertile of normal range) 1
   • Dose adjustment criteria:

     • 750 ng/dL: Decrease dose

     • 350-750 ng/dL: Continue current dose
     • <350 ng/dL: Increase dose 2

5. Monitor:

   • Initial monitoring (3-6 months): Testosterone levels, hematocrit, PSA, symptom response
   • Long-term monitoring (annually): Testosterone levels, hematocrit, PSA (in men ≥40 years), symptom evaluation 1
   • Action thresholds:
     • Discontinue if hematocrit exceeds 54% (consider therapeutic phlebotomy)
     • Prostate biopsy if PSA >4.0 ng/mL or increases >1.0 ng/mL/year 1
     • Discontinue if no improvement in sexual function within 12 months 1

Administration Instructions for Testosterone Gel

• Apply to clean, dry, intact skin of upper arms and shoulders only
• Cover application site with clothing once dry
• Wash hands thoroughly with soap and water after application
• Avoid swimming/showering for minimum 2 hours after application
• Keep children away from unwashed application sites 2

Potential Adverse Effects

• Erythrocytosis (increased red blood cell count)
• Fluid retention
• Prostate effects requiring monitoring
• Mood swings, hypertension
• Skin irritation, gynecomastia
• Potential for blood clots 1

Alternative Treatments

For patients who wish to avoid exogenous testosterone, are not candidates for TRT, or cannot tolerate adverse effects:

• Clomiphene citrate (25 mg daily) can effectively elevate endogenous testosterone levels and improve testosterone/estradiol ratio 4

Lifestyle Modifications

• Weight management
• Regular exercise
• Mediterranean diet
• Limiting alcohol consumption to less than 21 units per week 1

Important Caveats

• TRT is not recommended to improve energy, vitality, physical function, or cognition 1
• Safety and efficacy of testosterone gel in men with "age-related hypogonadism" have not been established 2
• Long-term safety data on cardiovascular outcomes remains limited, though recent evidence does not support a relationship between TRT and cardiovascular/cerebrovascular events in the short-to-medium term 5