What is the interpretation of low free and bioavailable testosterone levels in the context of hypogonadism diagnosis?

Interpretation of Low Free and Bioavailable Testosterone Levels

The patient's laboratory results indicate hypogonadism requiring further evaluation, as both free testosterone (5.56 ng/dL) and bioavailable testosterone (130 ng/dL) are below the reference range, despite a total testosterone level (268 ng/dL) within the lower normal range. 1

Laboratory Interpretation

• Total testosterone: 268 ng/dL (reference range: 240-871 ng/dL)

  • Within normal range but at the lower end

• Sex Hormone Binding Globulin (SHBG): 29.7 nmol/L (reference range: 11.2-78.1 nmol/L)

  • Within normal range

• Free testosterone: 5.56 ng/dL (reference range: 5.60-21.00 ng/dL)

  • Marginally below the reference range

• Bioavailable testosterone: 130 ng/dL (reference range: 131-682 ng/dL)

  • Marginally below the reference range

Clinical Significance

These results represent a classic case of "normal total testosterone with low free/bioavailable testosterone," which can be clinically significant. According to current guidelines:

1. The American College of Physicians recommends using a total testosterone threshold of <300 ng/dL for diagnosing hypogonadism in older men 1, while the Endocrine Society (noted in the lab comment) suggests <200 ng/dL.

2. However, free and bioavailable testosterone levels are often more clinically relevant than total testosterone for diagnosing hypogonadism, particularly when SHBG levels are normal or elevated 2.

3. The patient's free and bioavailable testosterone levels are both below the reference range, suggesting that despite a "normal" total testosterone, the patient may have functionally low testosterone.

Diagnostic Considerations

• A single measurement is insufficient for diagnosis. Current guidelines recommend measuring testosterone levels on at least two separate mornings to confirm consistently low levels 1.

• The time of collection is important - testosterone levels are highest in the morning and should be measured then for accurate assessment 1.

• The patient's symptoms should be evaluated alongside these laboratory values, including:

  • Sexual symptoms (reduced libido, erectile dysfunction)
  • Physical symptoms (fatigue, reduced muscle mass, increased body fat)
  • Psychological symptoms (depression, irritability, poor concentration)

Management Approach

If hypogonadism is confirmed with a second measurement and correlated with symptoms:

1. Determine the cause: Primary (testicular) vs. secondary (pituitary/hypothalamic) hypogonadism by measuring luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

2. Consider testosterone replacement therapy (TRT) if symptomatic and without contraindications. The American College of Physicians recommends TRT for men with age-related low testosterone who have sexual dysfunction and want to improve sexual function 1.

3. Monitor therapy: If TRT is initiated, monitor:

   • Testosterone levels (target: 450-600 ng/dL)
   • Hematocrit (discontinue if >54%)
   • PSA (in men ≥40 years)
   • Symptom response 1

Important Caveats

• Contraindications to TRT include breast or prostate cancer, hematocrit >50%, severe untreated sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, or desire for current/future fertility 1.

• Potential adverse effects include erythrocytosis, fluid retention, prostate effects, mood swings, hypertension, and skin irritation 1.

• Lifestyle modifications such as weight management, regular exercise, and a Mediterranean diet may help improve testosterone levels, particularly in men with high SHBG 1.

In this case, the discrepancy between normal total testosterone and low free/bioavailable testosterone highlights the importance of measuring all three parameters when evaluating for hypogonadism, as relying solely on total testosterone may miss clinically significant testosterone deficiency.