Endocrine Abstracts (2005) 10 P76

Free testosterone calculation: critical comparison of three equations and establishment of reference limits

CKM Ho1, M Stoddart2, M Walton2, RA Anderson1 & GJ Beckett1

1University of Edinburgh, Edinburgh, United Kingdom , 2Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.


Serum testosterone remains the most important investigation in the diagnosis of androgen deficiency in men. Most of the circulating testosterone is bound to albumin and sex hormone binding globulin (SHBG), whereas free testosterone accounts for approximately 2% of total testosterone. Because direct measurement of free testosterone is impractical in routine practice, several equations have been used to provide clinically useful estimates of free testosterone concentration.


This study aimed to (1) obtain locally derived reference limits for total testosterone and calculated free testosterone (CFT) concentrations, and (2) critically evaluate the equations commonly used to estimate CFT.


Serum total testosterone (Centaur, Bayer Healthcare, Berks), SHBG (Immulite 2000, DPC, Gwynedd) and albumin were assayed in morning blood samples obtained from 116 healthy men (aged 20–45) with ethical approval and written consent. CFT concentrations were calculated using three published methods i.e. the Sodergard, Nanjee-Wheeler and Vermeulen equations.


CFT concentrations varied considerably with the three equations examined, although correlation coefficients (R) ranged from 0.92 to 0.97. Difference plots showed that CFT values using the Nanjee-Wheeler equation were positively biased against those using the Sodergard and Vermeulen equations by 13.8+/−7.8% and 19.9+/−7.4% (mean+/−SD) respectively. Using the Vermeulen equation, lower reference limit of CFT for the diagnosis of androgen deficiency was 230 pmol/L (156–304 pmol/L, 90% confidence interval). Reference range for total testosterone was 9.2–31.5 nmol/L (2.5–97.5 percentile). Free androgen index (total testosterone x 100/SHBG), commonly used to estimate free testosterone concentration in women, correlated poorly with CFT (R=0.30–0.46) and over-estimated free testosterone at low SHBG concentrations. For the investigation of suspected androgen deficiency in men, we propose an algorithm using these reference limits of total testosterone and CFT which have not been rigorously defined previously in the UK.

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