What blood panels are most useful to diagnose low testosterone in men?

Diagnostic Blood Panels for Low Testosterone in Men

The most useful blood panels for diagnosing low testosterone in men include early morning total testosterone measurements on at least two separate occasions, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and estradiol in specific cases. 1

Primary Diagnostic Tests

• Total testosterone: Must be measured in the early morning (before 11:00 AM) on at least two separate occasions, preferably using the same laboratory with the same method/instrumentation 1, 2, 3
• Free testosterone: Should be measured when total testosterone is near the lower limit of normal or when sex hormone-binding globulin (SHBG) abnormality is suspected 1, 4
• SHBG: Particularly important in obese patients, as obesity can lower SHBG levels, affecting total testosterone measurements while free testosterone may remain normal 1

Secondary Diagnostic Tests

• Luteinizing hormone (LH): Essential to determine the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 1
• Follicle-stimulating hormone (FSH): Helps distinguish primary from secondary hypogonadism 5
• Prolactin: Should be measured in patients with low testosterone combined with low or low/normal LH levels to screen for hyperprolactinemia 1
• Estradiol: Should be measured in testosterone deficient patients who present with breast symptoms or gynecomastia 1

Diagnostic Thresholds and Timing

• Threshold for low testosterone: Consistently <300 ng/dL on at least two measurements 1
• Age-specific considerations: Young men (20-44 years) may have higher normative ranges, with age-specific cutoffs ranging from 350-413 ng/dL depending on exact age group 6
• Timing: Blood samples should be collected in the morning before 11:00 AM due to diurnal variation in testosterone production 2, 3
• Fasting state: Ideally measured in a fasting state for most accurate results 2

Special Considerations

• Repeat testing: When initial testosterone levels are in the equivocal range (7.0-12.5 nmol/L or approximately 200-360 ng/dL), at least one more measurement should be obtained due to significant intra-individual variability 3
• Laboratory method: Liquid chromatography tandem mass spectrometry is preferred for accuracy, especially in borderline cases 2
• Pituitary MRI: Consider when total testosterone is <150 ng/dL with low/normal LH levels, as non-secreting adenomas may be present 1, 5

Diagnostic Algorithm

1. Measure morning total testosterone level (before 11:00 AM) 1, 3
2. If total testosterone is <300 ng/dL, repeat the measurement on a different morning 1
3. If consistently low total testosterone is confirmed, measure LH and FSH 1
4. If LH/FSH are low or low/normal (suggesting secondary hypogonadism), measure prolactin 1
5. If prolactin is elevated, repeat measurement to confirm 1
6. If persistently elevated prolactin or if testosterone is <150 ng/dL with low/normal LH, consider pituitary MRI 1
7. If breast symptoms or gynecomastia are present, measure estradiol 1
8. In obese patients or those with suspected SHBG abnormalities, measure free testosterone and SHBG 1

Common Pitfalls to Avoid

• Single measurements: Relying on a single testosterone measurement is insufficient for diagnosis due to significant day-to-day variations 1, 3
• Afternoon measurements: Testosterone levels are naturally lower in the afternoon/evening, potentially leading to false diagnoses 3
• Ignoring age: Using the same cutoff (300 ng/dL) for all age groups may be inappropriate, especially for younger men who typically have higher baseline levels 6
• Screening questionnaires: These should not replace laboratory testing due to variable specificity and sensitivity 1
• Overlooking SHBG variations: In obesity, total testosterone may be low while free testosterone remains normal due to decreased SHBG 1