What is the evaluation and treatment process for low basal testosterone levels, also known as hypogonadism?

Evaluation and Treatment of Low Basal Testosterone Levels (Hypogonadism)

The diagnosis of testosterone deficiency requires both consistently low testosterone levels (<300 ng/dL on at least two early morning measurements) and the presence of specific symptoms and/or signs, with treatment recommended for symptomatic men to improve quality of life and reduce morbidity. 1

Diagnostic Evaluation

Clinical Assessment

• Symptoms to evaluate:

  • Reduced energy and endurance
  • Diminished work/physical performance
  • Fatigue
  • Depression and reduced motivation
  • Poor concentration and impaired memory
  • Irritability
  • Reduced sex drive
  • Changes in erectile function
  • Infertility 1

• Physical examination findings:

  • Body habitus and virilization status
  • Body mass index/waist circumference
  • Gynecomastia
  • Testicular size, consistency, and masses
  • Presence of varicocele
  • Prostate size and morphology 1

Laboratory Testing

1. Initial testing:

   • Measure total testosterone in early morning (preferably using same laboratory)
   • Confirm with repeat measurement if low
   • Threshold for low testosterone: <300 ng/dL on at least two measurements 1

2. Secondary testing:

   • Measure luteinizing hormone (LH) levels to establish etiology (primary vs. secondary hypogonadism) 1
   • Measure serum prolactin if testosterone is low with low/normal LH 1
   • Consider free testosterone measurement if total T is borderline low or if conditions affecting sex hormone-binding globulin (SHBG) are present 2, 3

3. Normal reference ranges:

   • Total testosterone: 300-950 ng/dL
   • Free testosterone: 50-200 pg/mL
   • SHBG: 10-50 nmol/L 2

High-Risk Populations

Measure testosterone levels in men with:

• Unexplained anemia
• Bone density loss
• Diabetes
• Exposure to chemotherapy or testicular radiation
• HIV/AIDS
• Chronic narcotic use
• Male infertility
• Pituitary dysfunction
• Chronic corticosteroid use 1

Treatment Approach

Testosterone Replacement Therapy (TRT)

• Indications: Men with symptoms and consistently low testosterone levels 1, 3
• Target range: 450-600 ng/dL 2
• Benefits: Improved sexual function, enhanced well-being, increased lean body mass, decreased body fat, increased bone density 2, 4

Contraindications for TRT

• Breast or prostate cancer
• Palpable prostate nodule or induration
• PSA >4.0 ng/mL (or >3.0 ng/mL in high-risk men)
• Elevated hematocrit (>50%)
• Severe untreated sleep apnea
• Severe lower urinary tract symptoms
• Uncontrolled heart failure
• Recent myocardial infarction or stroke (within 6 months)
• Thrombophilia
• Current or future fertility desires (with traditional TRT) 2, 5, 3

Monitoring During Treatment

1. Initial monitoring (3-6 months):

   • Testosterone levels
   • Hematocrit (discontinue if >54%)
   • PSA (consider biopsy if >4.0 ng/mL or increases >1.0 ng/mL/year)
   • Symptom response 2, 3

2. Long-term monitoring (annually):

   • Testosterone levels
   • Hematocrit
   • PSA (in men ≥40 years)
   • Symptom evaluation 2, 4

Special Considerations

Liver Function and SHBG

• High SHBG can affect testosterone bioavailability
• Liver disease can increase SHBG synthesis
• Consider liver function assessment in patients with abnormal SHBG 2
• Prolonged use of oral 17-alpha-alkyl androgens (not testosterone gel) has been associated with serious hepatic adverse effects 5

Cardiovascular Risk

• Recent evidence suggests TRT does not increase risk of myocardial infarction or stroke, even in high-risk patients 4
• Use caution in men with pre-existing cardiac conditions 2
• Delay TRT for 3-6 months after acute cardiovascular events 2

Potential Adverse Effects

• Increased PSA (most common)
• Emotional lability
• Hypertension
• Increased hematocrit
• Contact dermatitis
• Edema
• Gynecomastia
• Sleep apnea exacerbation
• Lipid profile changes 5

Pitfalls to Avoid

1. Do not diagnose based on symptoms alone - both low testosterone measurements and symptoms are required 1
2. Do not rely on screening questionnaires - these vary in sensitivity/specificity and are not recommended for diagnosis 1
3. Do not miss secondary causes - always measure LH to determine if hypogonadism is primary or secondary 1
4. Do not overlook high-risk conditions - screen for testosterone deficiency in men with specific risk factors even without symptoms 1
5. Do not ignore potential testosterone abuse - consider this possibility in patients with serious cardiovascular or psychiatric adverse events 5

By following this structured approach to evaluation and treatment, clinicians can effectively diagnose and manage testosterone deficiency while minimizing risks and optimizing outcomes.