Bioavailable Testosterone Lab Values
The lower normal limit for bioavailable testosterone in adult men is approximately 2.30-2.72 nmol/L (66-78 ng/dL) when measured by ammonium sulfate precipitation, based on a large reference population of healthy men aged 20-74 years. 1
Reference Ranges by Measurement Method
Measured Bioavailable Testosterone (Direct Assay)
- Lower normal limit: 2.30-2.72 nmol/L in men ≤39 years old 1
- This represents the assayed bioavailable testosterone (aBT) after ammonium sulfate precipitation, which is considered the reference method 1
- Values decline with age, with significant decreases observed in older populations 1
Calculated Bioavailable Testosterone
- Calculated values vary substantially depending on the algorithm used 2
- Mean calculated bioavailable testosterone ranges from 3.87 to 10.4 nmol/L depending on which published algorithm is applied 2
- The Sodergard algorithm produces the highest values (mean 10.4 nmol/L), while the Emadi-Konjin algorithm produces the lowest (mean 3.87 nmol/L) 2
- Calculated bioavailable testosterone at a threshold of 0.78 nmol/L showed diagnostic utility in PCOS studies (sensitivity 0.76, specificity 0.83), though this population differs from adult males 3
Clinical Context for Interpretation
When to Measure Bioavailable Testosterone
- Bioavailable testosterone measurement is most useful when total testosterone falls between 6.5-13.0 nmol/L (187-375 ng/dL) 4
- Outside this range, total testosterone alone provides sufficient diagnostic information 4
- In men with diabetes who have total testosterone levels close to the lower limit, free or bioavailable testosterone should be measured due to expected decreases in sex hormone-binding globulin 3
Key Measurement Considerations
- Morning fasting samples are essential for accurate assessment, as testosterone levels fluctuate throughout the day 5
- Bioavailable testosterone represents unbound testosterone plus albumin-bound testosterone, reflecting the readily dissociable and biologically available fraction 6
- Only 0.5-3% of circulating testosterone is free, with the remainder bound to SHBG (60%) and albumin (38%) 6
Algorithm Discrepancies and Pitfalls
Calculation Method Variability
- Different published algorithms produce results that differ by up to 2.7-fold 2
- The association constants used (Ks for SHBG and Ka for albumin) dramatically affect calculated values 1
- Standard constants (Ks = 1×10⁹ L/mol, Ka = 3.6×10⁴ L/mol) produce calculated values approximately 2-fold higher than measured values 1
- Optimized constants (Ks = 1.9×10⁹ L/mol, Ka = 2.45×10⁴ L/mol) provide better correlation with measured values 1
SHBG Confounding
- Many calculated bioavailable testosterone algorithms remain significantly associated with SHBG concentrations, introducing potential confounding 2
- Androstenediol (5-diol) acts as a competitive SHBG inhibitor and should be considered in calculations for improved accuracy 1
- SHBG alterations can significantly affect total testosterone concentrations, making bioavailable testosterone measurement critical in certain clinical scenarios 6
Diagnostic Thresholds in Clinical Practice
Hypogonadism Diagnosis
- Total testosterone <8 nmol/L (230 ng/dL) highly supports hypogonadism diagnosis 7
- Total testosterone >12 nmol/L (346 ng/dL) is likely normal 7
- The "gray zone" of 8-12 nmol/L (230-346 ng/dL) requires evaluation of free or bioavailable testosterone 7
- This gray zone represents approximately 90% of cases where bioavailable testosterone measurement adds diagnostic value 4