What is the initial workup for a male presenting with symptoms suggestive of low testosterone?

Initial Workup for Low Testosterone in Males

The initial workup for a male presenting with symptoms suggestive of low testosterone should include morning serum total testosterone measurements on at least two separate occasions between 8-10 AM, followed by free testosterone, LH, and FSH if total testosterone is low, to distinguish between primary and secondary hypogonadism. 1

Step 1: Clinical Assessment

• Evaluate for symptoms and signs suggestive of testosterone deficiency:
  • Decreased energy and libido
  • Reduced muscle mass
  • Loss of body hair
  • Hot flashes
  • Gynecomastia
  • Infertility
  • Erectile dysfunction (especially if PDE5 inhibitors have failed) 1

Step 2: Initial Laboratory Testing

• Morning total testosterone measurement (between 8-10 AM when levels are highest)

  • Must be drawn in the morning due to diurnal variation 2, 1
  • Consider 300 ng/dL as the reasonable cut-off for low testosterone 1
  • Normal range for adult men: 300-950 ng/dL 1

• If initial total testosterone is low:

  • Repeat morning total testosterone on a separate day to confirm 2, 1, 3
  • Diagnosis requires at least two separate morning measurements showing low levels 1

Step 3: Additional Testing for Confirmed Low Total Testosterone

• Free testosterone measurement (especially important in obese patients)

  • Normal range: 50-200 pg/mL 1
  • Equilibrium dialysis method preferred for accuracy 2
  • Essential in obese patients as they may have low total testosterone due solely to low SHBG but normal free testosterone 2

• Sex hormone-binding globulin (SHBG) level

  • Normal range: 10-50 nmol/L 1
  • Particularly important in obesity, liver disease, hyperthyroidism, or other conditions that affect SHBG 2

• Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH)

  • Critical to distinguish primary from secondary hypogonadism 2, 3
  • Primary hypogonadism: Low testosterone with elevated LH/FSH (testicular failure)
  • Secondary hypogonadism: Low testosterone with low/normal LH/FSH (pituitary-hypothalamic dysfunction) 2, 4

Step 4: Further Evaluation Based on LH/FSH Results

If Secondary Hypogonadism (Low testosterone with low/normal LH/FSH):

• Serum prolactin measurement 2
• Iron saturation to rule out hemochromatosis 2
• Pituitary function testing (cortisol, thyroid function) 2
• MRI of sella turcica to evaluate for pituitary tumors or other abnormalities 2

If Primary Hypogonadism (Low testosterone with elevated LH/FSH):

• Evaluate for testicular disorders (cryptorchidism, orchitis, trauma) 4

Common Pitfalls and Caveats

• Single testosterone measurement is insufficient - always confirm with a second morning measurement 1, 3
• Timing matters - testosterone levels are highest in the morning; afternoon measurements may lead to false diagnoses 2, 1
• Obesity effect - obese men may have low total testosterone but normal free testosterone due to reduced SHBG 2
• Acute illness - can temporarily suppress testosterone; defer testing until resolution 5
• Contraindications for testosterone therapy must be evaluated before treatment:
  • Prostate or breast cancer
  • Hematocrit >50%
  • Severe untreated sleep apnea
  • Severe lower urinary tract symptoms (IPSS >19)
  • Uncontrolled heart failure 1, 6, 3
• Fertility concerns - testosterone replacement suppresses spermatogenesis and should be avoided in men desiring fertility 1

By following this systematic approach, clinicians can accurately diagnose testosterone deficiency and determine the appropriate next steps for management based on the underlying cause.