Calculated free testosterone: rightful heir to the free thyroxine index?

Area of Science:

• Endocrinology
• Andrology
• Clinical Chemistry

Background:

• Male hypogonadism diagnosis traditionally combines clinical symptoms with total testosterone (T) levels.
• Current androgen assessment faces challenges, mirroring historical issues with thyroxine (T4) measurements.
• Calculated free testosterone (cFT) is strongly correlated with androgen-sensitive outcomes, but its diagnostic utility is debated.

Purpose of the Study:

• To propose a pragmatic framework for diagnosing male hypogonadism.
• To advocate for the inclusion of calculated free testosterone (cFT) in diagnostic protocols.
• To outline a research agenda for further validating cFT.

Main Methods:

• Review of existing diagnostic approaches for male hypogonadism.
• Analysis of the role of total testosterone (T) and sex hormone-binding globulin (SHBG) in diagnosis.
• Evaluation of the evidence supporting calculated free testosterone (cFT) as a diagnostic marker.

Main Results:

• Critics question cFT validity, offering vague guidance on interpreting total testosterone (T) with SHBG.
• Omitting cFT from male hypogonadism workups disregards its ability to correct for SHBG variations.
• A proposed framework aims to standardize and improve the accuracy of hypogonadism diagnosis.

Conclusions:

• Calculated free testosterone (cFT) is a rational, evidence-based tool for diagnosing male hypogonadism.
• A standardized framework incorporating cFT is needed for accurate androgen assessment.
• Further research should validate cFT as a robust and accessible diagnostic method.