What is the initial workup for male hypogonadism?

Initial Workup for Male Hypogonadism

The initial workup for male hypogonadism requires measuring morning total testosterone levels on at least two separate days to confirm the diagnosis, along with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish between primary and secondary hypogonadism. 1, 2

Diagnostic Testing Algorithm

Step 1: Testosterone Measurement

• Measure fasting morning total testosterone between 8-10 AM on at least two separate occasions 2, 1, 3
• Diagnostic threshold: Total testosterone <300 ng/dL (10.41 nmol/L) 2, 1
• If total testosterone levels are borderline or if conditions affecting sex hormone-binding globulin (SHBG) exist:
  • Measure free testosterone by equilibrium dialysis (gold standard) 1
  • Or calculate free testosterone using total testosterone, SHBG, and albumin concentrations 2

Step 2: Gonadotropin Assessment

• Measure LH and FSH levels to determine the type of hypogonadism 1, 4:
  • Primary hypogonadism: Low testosterone with elevated LH/FSH
  • Secondary hypogonadism: Low testosterone with low/normal LH/FSH

Step 3: Additional Testing Based on Initial Results

• For secondary hypogonadism (low/normal LH/FSH):

  • Measure serum prolactin (Grade A recommendation) 1
  • Consider pituitary MRI if prolactin is elevated or if severe hypogonadism is present 1
  • Assess other pituitary hormones (TSH, free T4, morning cortisol) 4

• For all patients:

  • Complete blood count (hemoglobin/hematocrit) 1
  • Prostate-specific antigen (PSA) in men >40 years 1
  • Bone mineral density if risk factors for osteoporosis exist 1

Clinical Assessment

Symptoms and Signs to Evaluate

• Sexual symptoms:

  • Decreased libido
  • Erectile dysfunction
  • Decreased frequency of morning erections 1

• Physical symptoms:

  • Fatigue/lethargy
  • Decreased muscle mass and strength
  • Increased body fat
  • Decreased body hair
  • Hot flashes/sweats 2, 1

• Cognitive/psychological symptoms:

  • Depressed mood
  • Decreased sense of well-being
  • Reduced cognitive function 1, 5

Physical Examination

• Body mass index (BMI) and waist circumference
• Gynecomastia
• Hair pattern and distribution
• Testicular size (using orchidometer)
• Prostate examination (digital rectal exam) 1, 4

Important Considerations

Rule Out Transient Causes

Before confirming diagnosis, exclude conditions that temporarily suppress testosterone 4:

• Acute illness
• Medications (opioids, glucocorticoids, anabolic steroids)
• Excessive exercise
• Sleep deprivation
• Nutritional deficiencies

Identify Underlying Causes

Common causes to consider 2:

• Primary hypogonadism:

  • Klinefelter syndrome
  • Testicular trauma/surgery
  • Chemotherapy/radiation
  • Mumps orchitis

• Secondary hypogonadism:

  • Pituitary tumors
  • Hyperprolactinemia
  • Hemochromatosis
  • Obesity
  • Chronic systemic illness

Pitfalls to Avoid

• Timing error: Not measuring testosterone in the morning (8-10 AM) when levels are highest 3
• Single measurement: Relying on just one testosterone measurement 2, 3
• Ignoring SHBG variations: Not accounting for conditions that alter SHBG (obesity, diabetes, liver disease, thyroid disorders) 2, 1
• Missing functional causes: Not evaluating for reversible causes like obesity, medications, or chronic illness 1
• Overlooking fertility concerns: Not discussing fertility preservation in men of reproductive age 1

By following this systematic approach, clinicians can accurately diagnose male hypogonadism and determine its etiology, which is essential for appropriate treatment planning.