Interpretation of Lab Results with Low Total Testosterone but Normal Free and Bioavailable Testosterone
No testosterone replacement therapy is needed for this patient with low total testosterone but normal free and bioavailable testosterone levels, as the clinical diagnosis of testosterone deficiency requires both low testosterone levels and symptoms.1
Laboratory Interpretation
- Total testosterone is low at 5.5 nmol/L (reference range: 8.4-28.8 nmol/L) 1
- Free testosterone is normal at 122 pmol/L (reference range: 115-577 pmol/L) 1, 2
- Bioavailable testosterone is normal at 2.9 nmol/L (reference range: 2.7-13.5 nmol/L) 1
- Sex Hormone Binding Globulin (SHBG) is normal at 24.3 nmol/L (reference range: 19.0-76.0 nmol/L) 1
Clinical Significance
- Free testosterone is a better indicator of gonadal status than total testosterone and should be prioritized in clinical decision-making 2, 3
- The discrepancy between low total testosterone and normal free/bioavailable testosterone suggests normal androgen activity despite low total levels 2, 3
- This pattern can occur due to variations in SHBG levels, which affect the amount of testosterone bound versus free in circulation 2, 3
- A clinical diagnosis of testosterone deficiency requires both low testosterone levels AND symptoms/signs of hypogonadism 1
Recommended Course of Action
- No immediate testosterone replacement therapy is needed since free and bioavailable testosterone levels are normal 1, 2
- Repeat morning total testosterone measurements on a separate occasion to confirm the low level, as recommended by guidelines 1
- Assess for symptoms of hypogonadism such as reduced energy, reduced endurance, fatigue, depression, poor concentration, infertility, reduced sex drive, and erectile dysfunction 1
- Measure luteinizing hormone (LH) levels to help establish the etiology of testosterone deficiency if symptoms are present 1
Special Considerations
- If symptoms of hypogonadism are present despite normal free testosterone, consider other potential causes of these symptoms 4, 5
- Avoid initiating testosterone therapy based solely on a single low total testosterone measurement without symptoms 4, 6
- Consider the patient's age, as the prevalence of elevated SHBG increases after age 60, which can lead to low total testosterone despite normal free testosterone 3
- If treatment is eventually deemed necessary, clomiphene citrate might be considered as an alternative to testosterone replacement therapy, particularly if fertility preservation is desired 7, 5
Potential Pitfalls to Avoid
- Treating based on total testosterone levels alone without considering free testosterone levels 3
- Failing to distinguish between primary and secondary hypogonadism, which require different management approaches 2
- Not considering other causes of similar symptoms before attributing them to testosterone deficiency 2, 4
- Initiating testosterone therapy without confirming low testosterone with repeated morning measurements 4