What are the diagnostic criteria for testosterone deficiency?

Diagnostic Criteria for Testosterone Deficiency

Testosterone deficiency should be diagnosed based on both clinical symptoms and biochemical evidence, with total testosterone levels <300 ng/dL measured between 8-10 AM on at least two separate occasions considered diagnostic. 1

Clinical Symptoms and Signs

Testosterone deficiency syndrome (TDS) presents with various symptoms depending on age of onset:

• Adult-onset symptoms:

  • Decreased sexual desire and activity
  • Erectile dysfunction
  • Low energy and fatigue
  • Mood disturbances
  • Reduced muscle mass
  • Increased adipose tissue
  • Decreased bone mineral density 1, 2

• Prepubertal-onset symptoms:

  • Lack of virilization
  • Delayed pubertal development
  • Eunuchoid body proportions
  • Underdeveloped secondary sex characteristics 3

Biochemical Assessment

Primary Measurements

• Total testosterone:

  • Must be measured between 8-10 AM to account for diurnal variation
  • Requires at least two morning fasting samples
  • <300 ng/dL (or <8 nmol/L) is generally considered low
  • Levels between 8-12 nmol/L represent a "grey zone" requiring additional testing 1, 3

• Free testosterone:

  • Should be measured by equilibrium dialysis (gold standard)
  • Particularly important in obese patients or those with altered SHBG
  • Free testosterone index (total testosterone/SHBG ratio) < 0.3 indicates hypogonadism 1, 4

Additional Testing

• Sex hormone-binding globulin (SHBG):

  • Essential to determine bioavailable testosterone
  • Helps interpret total testosterone in conditions affecting SHBG levels 1

• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH):

  • Helps determine the type of hypogonadism:
    • High LH/FSH: Primary hypogonadism (testicular failure)
    • Low/normal LH/FSH: Secondary hypogonadism (pituitary/hypothalamic disorder) 1, 5

Laboratory Quality Considerations

• Testing should be performed in laboratories certified by accuracy-based programs (e.g., CDC's Hormone Standardization Program)
• Liquid chromatography-tandem mass spectrometry is the most accurate method for testosterone measurement 4

Common Pitfalls and Considerations

1. Underdiagnosis: TDS is frequently underdiagnosed, with prevalence ranging from 6-9.5% in men aged 40-70 years, and 15-30% in diabetic or obese men 6

2. Medication-induced hypogonadism: Several medications can cause testosterone deficiency:

   • Opioids (especially methadone)
   • Glucocorticoids
   • Antipsychotics (particularly olanzapine, quetiapine, and risperidone) 1

3. Conditions associated with higher prevalence:

   • Metabolic syndrome
   • Type 2 diabetes
   • Obesity
   • Chronic infections
   • Inflammatory diseases
   • COPD
   • Cardiovascular disease 3

4. Questionnaires: Not useful for screening but may help with diagnosis and follow-up 2

5. Contraindications for treatment: Active prostate cancer, stage IV heart failure, breast cancer, desired fertility, and hematocrit values over 54% 2, 7

The diagnostic approach requires both clinical and biochemical evidence, with careful attention to proper laboratory testing techniques and consideration of factors that may affect testosterone levels. Multiple societies including the American Urological Association, European Association of Urology, and the Endocrine Society agree that only men meeting both clinical and biochemical criteria should be treated 7.