Assessment of free testosterone concentration

Area of Science:

• Endocrinology
• Clinical Chemistry

Background:

• Free hormone hypothesis suggests free testosterone (T) measurement is superior to total T for assessing androgen status.
• This remains controversial, though supported by recent clinical guidelines for androgen disorders.

Purpose of the Study:

• To evaluate the utility and challenges of free testosterone measurement and calculation methods.
• To discuss the implications for diagnosing androgen disorders.

Main Methods:

• Review of existing literature on free and total testosterone assays.
• Analysis of algorithms and equations for calculating free testosterone.
• Discussion of the limitations of current measurement and calculation techniques.

Main Results:

• Direct measurement of free T is complex and lacks assay harmonization, hindering routine clinical use.
• Calculated free T algorithms, though imperfect, can provide clinically useful results.
• The free androgen index is unreliable, especially at extreme sex hormone-binding globulin (SHBG) concentrations.

Conclusions:

• Calculated free testosterone may be the most practical approach if the free hormone hypothesis holds true.
• Improved equations derived from detailed testosterone-SHBG binding knowledge are needed.
• Harmonization of testosterone and SHBG assays is crucial for accurate free T calculation.