Laboratory Tests for Evaluating Low Testosterone
The diagnosis of low testosterone requires two early morning total testosterone measurements below 300 ng/dL on separate occasions, combined with symptoms and/or signs of testosterone deficiency. 1
Initial Laboratory Evaluation
- Measure total testosterone in an early morning fashion (8-10 AM) when levels are highest due to diurnal variation 1
- Confirm with a second early morning total testosterone measurement on a separate occasion, preferably using the same laboratory with the same method/instrumentation 1
- Total testosterone below 300 ng/dL is the recommended cut-off to support the diagnosis of low testosterone 1
Additional Required Testing
- Measure serum luteinizing hormone (LH) levels to establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 1
- Measure serum prolactin levels in patients with low testosterone combined with low or low/normal LH levels 1
- Consider measuring free testosterone by equilibrium dialysis or calculation when total testosterone is near the lower limit of normal or when SHBG abnormality is suspected 2, 3
Special Considerations for Free Testosterone
- Total testosterone alone may not be sufficient to exclude hypogonadism, particularly in men over 60 years old or those with conditions that alter SHBG 4
- Total testosterone must exceed 350-400 ng/dL to reliably predict normal free testosterone 5
- In patients with normal SHBG but reduced total testosterone, free testosterone measurement is essential to determine if true testosterone deficiency exists 2
Clinical Context for Testing
- Document symptoms associated with low testosterone: reduced energy, reduced endurance, diminished work/physical performance, fatigue, visual field changes, anosmia, depression, reduced motivation, poor concentration, impaired memory, irritability, infertility, reduced sex drive, and erectile dysfunction 1
- Conduct targeted physical exam: body habitus, virilization status, BMI/waist circumference, gynecomastia, testicular evaluation, varicocele presence, and prostate assessment 1
High-Risk Populations
Consider measuring total testosterone even in asymptomatic patients with:
- Unexplained anemia 1
- Bone density loss 1
- Diabetes 1
- Exposure to chemotherapy or testicular radiation 1
- HIV/AIDS 1
- Chronic narcotic or corticosteroid use 1
- Male infertility 1
- Pituitary dysfunction 1
Common Pitfalls
- Validated questionnaires are not recommended for identifying candidates for testosterone therapy due to variable specificity and sensitivity 1
- Single testosterone measurements are insufficient; confirmation with a second measurement is required 1
- Normal total testosterone does not exclude hypogonadism in men with elevated SHBG, particularly in older men 6, 4
- Morning measurements are essential due to diurnal variation in testosterone levels 1
- Free androgen index correlates poorly with calculated free testosterone and may overestimate free testosterone at low SHBG concentrations 7