Calculated free testosterone in men: comparison of four equations and with free androgen index

Ann Clin Biochem 2006;43:389-397
© 2006 Association for Clinical Biochemistry


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Original Articles

Clement KM Ho,
Mary Stoddart,
Melanie Walton,
Richard A Anderson and
Geoffrey J Beckett

Department of Reproductive and Developmental Sciences, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh EH16 4SA, UK;
Department of Clinical Biochemistry, Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh EH16 4SA, UK

Background: Serum testosterone remains the most important investigationin the diagnosis of androgen deficiency in men. Most of thecirculating testosterone is bound to albumin and sex hormone-bindingglobulin (SHBG), whereas free testosterone accounts for approximately2% of total testosterone. Because direct measurement of freetestosterone is impractical in routine practice, several equationsare used to provide clinically useful estimates of free testosteroneconcentration. This study aimed to (1) obtain locally derivedreference limits for total testosterone and calculated freetestosterone (CFT) concentrations, and (2) critically evaluatethe equations commonly used to estimate free testosterone.

Methods: Serum total testosterone, SHBG and albumin were assayedin morning blood samples obtained from 126 healthy men (aged20-45 years) known to have normal semen analysis. CFT concentrationscalculated using four published methods (i.e. the Sodergard,Nanjee-Wheeler, Vermeulen and Ly-Handelsman equations) werecompared with one another and the free androgen index.

Results: Reference intervals for total testosterone and CFT by the Vermeulen equation were 9.4-31.0 nmol/L and 0.245-0.785 nmol/L (2.5-97.5 percentile), respectively. CFT values varied considerably with the four equations examined. Mean biases ranged from 5.8 to 56.0%; the Nanjee-Wheeler and Ly-Handelsman equations yielded positive and negative biases, respectively, against the other equations. Free androgen index was shown to correlate poorly with CFT (r2 = 0.21-0.46) and over-estimate the CFT atlow SHBG concentrations.

Conclusions: We have used various equations to derive referenceranges for CFT in healthy men aged 20-45 years. We suggest thatCFT be incorporated into the investigation regimen for suspectedhypogonadism when total testosterone results are equivocal.

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