What lab tests are recommended for evaluating low testosterone in males?

Laboratory Evaluation for Low Testosterone in Males

Morning total testosterone measurement is the primary initial test for evaluating low testosterone in males, with repeat measurement required for confirmation before diagnosis. 1

Initial Laboratory Testing

• Total testosterone level:

  • Must be measured in the morning (when levels are highest)
  • Should be measured on at least two separate days 1, 2
  • Fasting samples are preferred 2
  • Target reference range for therapy: 450-600 ng/dL 1

• Additional baseline tests:

  • Hematocrit or hemoglobin (baseline and monitoring) 1
  • PSA (in men over 40) 1

Secondary Testing (If Initial Total Testosterone is Low)

When total testosterone is near the lower limit of normal or if conditions affecting sex hormone-binding globulin (SHBG) are present:

• Free testosterone measurement using:

  • Equilibrium dialysis (gold standard) or
  • Calculated free testosterone using an accurate formula 2

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

  • Essential to distinguish between primary hypogonadism (high LH/FSH) and secondary hypogonadism (normal/low LH/FSH) 3, 4
  • Helps determine the cause of testosterone deficiency 2

• Prolactin level:

  • Particularly important if secondary hypogonadism is suspected 4

Age-Specific Considerations

It's important to note that testosterone levels vary by age, and using age-specific reference ranges may be more appropriate than a universal cutoff:

• Age 20-24: Low testosterone cutoff of 409 ng/dL
• Age 25-29: Low testosterone cutoff of 413 ng/dL
• Age 30-34: Low testosterone cutoff of 359 ng/dL
• Age 35-39: Low testosterone cutoff of 352 ng/dL
• Age 40-44: Low testosterone cutoff of 350 ng/dL 5

Additional Testing Based on Clinical Context

• Cardiovascular risk assessment:

  • Lipid profile
  • Blood pressure measurement
  • Assessment of other ASCVD risk factors 1

• For infertile men:

  • Semen analysis should be performed before testosterone therapy, as exogenous testosterone suppresses spermatogenesis 4, 6

Monitoring During Testosterone Therapy

If testosterone replacement is initiated, follow-up testing should include:

• Total testosterone: Check 2-3 months after starting therapy, then every 6-12 months 1
• Hematocrit: Monitor regularly, intervene if exceeds 54% 1
• PSA: Monitor in men over 40 1
• LH levels: May be suppressed during therapy, with 22-73% of men showing suppression at some point 6

Important Caveats

• Testosterone levels can be artificially lowered by systemic illness, so evaluation should occur when the patient is in a stable health state 7
• The FDA indicates that testosterone therapy is only approved for primary hypogonadism or hypogonadotropic hypogonadism, not for "age-related hypogonadism" 3
• Testing should be performed using accurate and reliable assays 2
• Testosterone therapy should not be initiated in men planning fertility in the near term 2

Remember that diagnosis of testosterone deficiency should only be made in men with both consistent symptoms and unequivocally low testosterone levels on repeated morning measurements.