Is 170 nmol/L the cut-off value for Sex Hormone-Binding Globulin (SHBG) levels when calculating free testosterone?

SHBG Values and Free Testosterone Calculation

The cutoff value of 170 nmol/L for Sex Hormone-Binding Globulin (SHBG) refers to the upper limit at which calculations of free testosterone lose diagnostic value due to excessive SHBG fluctuations. 1

Understanding Free Testosterone and SHBG

Free testosterone represents the unbound fraction of total testosterone that is biologically active and available to cells. When evaluating androgen status, particularly in cases with equivocal total testosterone results, free testosterone measurement becomes important.

• Free testosterone constitutes approximately 2% of total testosterone, with the remainder bound to albumin and SHBG 2
• Calculated free testosterone (cFT) is determined using mathematical formulas based on total testosterone, SHBG, and albumin levels 3
• When SHBG values exceed 170 nmol/L, the fluctuations are too high for reliable free testosterone calculations, diminishing diagnostic value 1

Clinical Implications of High SHBG

When SHBG levels are significantly elevated:

• Free testosterone calculations become unreliable and may not accurately reflect the biologically active testosterone 1
• Direct measurement methods such as equilibrium dialysis should be considered instead of calculated values 3
• Extremely high SHBG can artificially lower the calculated free testosterone, potentially leading to misdiagnosis 4

When to Calculate vs. Directly Measure Free Testosterone

Calculate Free Testosterone When:

• Total testosterone results are equivocal 1
• SHBG is within normal range (below 170 nmol/L) 1
• Routine clinical evaluation is needed 3

Consider Direct Measurement (Equilibrium Dialysis) When:

• SHBG exceeds 170 nmol/L 1
• Albumin is ≤3.5 g/dL combined with SHBG ≤30 nmol/L 3, 4
• High precision is required for clinical decision-making 2

Practical Approach to Testosterone Assessment

1. Begin with total testosterone measurement

   • If total testosterone is clearly low (<6.5 nmol/L) or normal (>13.0 nmol/L), additional free testosterone testing may be unnecessary 5
   • If total testosterone is borderline (6.5-13.0 nmol/L), proceed with SHBG measurement and free testosterone calculation 5

2. Check SHBG level

   • If SHBG is >170 nmol/L, calculated free testosterone will have limited diagnostic value 1
   • If SHBG is ≤170 nmol/L, calculated free testosterone can be reliably used 1

3. Consider albumin levels

   • For most clinical evaluations, using a fixed albumin value of 4.3 g/dL is acceptable 3, 4
   • When albumin is ≤3.5 g/dL with SHBG ≤30 nmol/L, direct measurement is preferred 3

Common Pitfalls in Free Testosterone Assessment

• Relying solely on Free Androgen Index (FAI) can lead to overestimation of free testosterone, particularly when SHBG is low 2
• Using calculated free testosterone when SHBG exceeds 170 nmol/L may result in inaccurate clinical assessment 1
• Failing to collect blood samples in the morning (8-10 AM) when testosterone levels are highest 6
• Not accounting for albumin levels in patients with hypoalbuminemia 3, 4

By understanding these limitations and following appropriate testing algorithms, clinicians can more accurately assess androgen status and avoid misdiagnosis of hypogonadism or hyperandrogenism.