Which Testosterone Measurement is Used to Diagnose Hypogonadism
Total testosterone measured on two separate mornings is the primary test used to diagnose hypogonadism, with a threshold below 300 ng/dL supporting the diagnosis. 1
Primary Diagnostic Test
- Morning total testosterone is the initial and primary measurement, obtained between 8-10 AM in a fasting state 1, 2
- Two separate measurements are mandatory to confirm the diagnosis, as testosterone levels fluctuate and assay variability exists 1, 3
- The diagnostic threshold is <300 ng/dL (some guidelines use 275-350 ng/dL range), measured using an accurate assay method 1, 2
- Liquid chromatography-tandem mass spectrometry performed in a CDC-certified laboratory (HoST Program) provides the most accurate measurement 3
When to Add Free Testosterone Measurement
Free testosterone becomes essential in specific clinical scenarios where total testosterone alone is unreliable:
- Men with borderline total testosterone in the "grey zone" of 230-350 ng/dL (8-12 nmol/L) 2
- Obese patients where altered SHBG levels may cause misleadingly low total testosterone 2, 4
- Conditions that alter SHBG including aging, liver disease, thyroid disorders, and certain medications 2, 5
- Free testosterone should be measured by equilibrium dialysis, which is the gold standard method 2, 3, 5
- Alternatively, calculate the free testosterone index (total testosterone/SHBG ratio), with values <0.3 indicating hypogonadism 2
Additional Required Measurements
Once low testosterone is confirmed, measure LH and FSH to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism, as this distinction has critical treatment implications including fertility preservation 2, 5
- Elevated LH/FSH with low testosterone = primary hypogonadism 2
- Low or low-normal LH/FSH with low testosterone = secondary hypogonadism 2
Critical Diagnostic Requirements
The diagnosis requires BOTH biochemical confirmation AND clinical symptoms/signs - testosterone levels alone are insufficient 1, 2:
- Reduced libido, erectile dysfunction, diminished energy, reduced endurance, fatigue, depression, poor concentration, or infertility 1
- Physical examination findings including reduced body hair, gynecomastia, small testes, or increased body fat 1
Common Pitfalls to Avoid
- Never diagnose based on a single measurement - diurnal variation and assay variability mandate confirmation 1, 3
- Never measure testosterone in the afternoon or evening when levels are physiologically lower 1, 2
- Never use screening questionnaires alone to diagnose hypogonadism, as they lack specificity 1, 2
- Never diagnose hypogonadism in men currently on testosterone therapy - exogenous testosterone suppresses the HPT axis and invalidates diagnostic testing 2
- In obese men with proportionately reduced testosterone and SHBG but normal LH/FSH, this represents pseudo-hypogonadism of obesity, not pathological hypogonadism requiring testosterone therapy 4