Understanding Free Testosterone: Why Accurate Measurement Still Matters

This summary highlights the challenges and controversies surrounding the measurement and calculation of free testosterone (FT).

This is based on a study by Keevil and Adaway of the University of Machester (2019). 

Here's a breakdown of the key points:

1. The Role of Free Testosterone

   • Measuring free testosterone (FT) can complement the measurement of total testosterone (T) in some clinical scenarios.
   • However, its utility is debated, and it is not universally accepted as a reliable measure in clinical practice.

2. Limitations of Laboratory Methods

   • Equilibrium dialysis is considered the gold standard for measuring FT but is too complex, labor-intensive, and costly for routine clinical use.

3. Issues with Existing Equations

   • Common equations used to estimate FT are inaccurate because they rely on flawed assumptions about how testosterone binds to SHBG.
   • These inaccuracies can lead to unreliable results, especially in specific populations or when SHBG levels are abnormal.

4. Challenges with the Free Androgen Index (FAI)

   • The Free Androgen Index (FAI), a quick calculation based on total testosterone and SHBG, is unreliable.
   • It becomes particularly inaccurate when SHBG levels are low, as seen in some medical conditions or hormonal disorders.

5. The Need for Better Models

   • There is a pressing need for improved mathematical models and equations to calculate FT.
   • These models must be based on a better understanding of testosterone’s interaction with SHBG and other proteins like albumin.

Implications for Clinical Practice

Until more accurate and practical methods are developed, clinicians must use a combination of tests and clinical judgment when assessing androgen levels. FT calculations should be interpreted with caution, considering the limitations of the current methods.