Total Testosterone and Calculated Estimates for Free and Bioavailable Testosterone: Influence of Age and Body Mass Index and Establishment of Sex-Specific Reference Ranges.

ABSTRACT

Measurement of sex steroids is required to evaluate gonadal function, but normative data are lacking (especially for estimates of physiologically active testosterone). Using modern immunoassays, this study established sex-specific reference ranges (2.5% and 97.5% percentiles) for total testosterone (TOT), bioactive testosterone Vermeulen (BTV), free androgen index (FAI), free testosterone Sartorius (FTS), free testosterone Vermeulen (FTV), and sex hormone binding globulin (SHBG). In the comparative study, subjects were grouped by age (18-30; 31-50; >50 years), BMI (<25; 25-30; >30 kg/m(2)), and sex. Study participants were selected in such a way that each group comprised 12 subjects (e.g., 12 males between 18 and 30 years with a BMI of <25 kg/m(2), and so on), resulting in a total of 216 controls (108 males, 108 females; age 40.3 ± 1.0; BMI 27.8 ± 0.4). Multiple stepwise regression analyses were performed (covariates age, BMI, sex), and sex-specific reference ranges were applied to 50 males (age 46.1 ± 2.3; BMI 27.4 ± 0.7) with suspected hypogonadism. Regression analysis identified the strongest predictor of each parameter apart from sex, resulting in age-specific (males FAI, SHBG, BTV, FTV; females TOT, FTS, SHBG), BMI-specific (males TOT, FTS; females FAI, BTV, FTV) and overall cutoffs for both sexes. In male patients, overall agreement between the results derived from the estimates (i.e., BTV, FTS, FTV) was high (with discordant results in only 4%). In summary, if both the endocrine workup and the clinical presentation were taken into account, the newly established reference ranges allowed reliable identification of hypogonadal males.