Validity of estimating non-sex hormone-binding globulin bound testosterone and oestradiol from total hormone measurements in boys and girls

Background: Circulating levels of bioavailable oestradiol and testosterone are often desirable for clinical practice or investigational studies of children. However, assays to measure circulating hormone levels might not always be accessible. We sought to validate the empirical calculation of circulating bioavailable testosterone and oestradiol in children. Methods: Six hundred and sixty-three eight- to 10-year olds were recruited to the Dietary Intervention Study in Children (DISC). DISC was a randomized clinical trial designed to test efficacy of a dietary intervention to reduce serum cholesterol (LDL-C) in children with elevated cholesterol. Assay measures of oestradiol, testosterone, sex hormone-binding globulin concentration (SHBG) and albumin concentration in girls as well as dihydrotestosterone in boys were measured for up to 10 y. We calculated measures of circulating non-SHBG bound oestradiol and testosterone from total hormone levels using the law of mass action. We compared proportional differences in assay measured minus calculated non-SHBG bound hormone levels versus their averages using generalized estimating equations-estimated linear regressions. Results: On average, calculated values overestimated assay measured values (-11.7% for non-SHBG bound oestradiol in girls and -2.6% for non-SHBG bound testosterone in boys). The intercept and slope of the regression for non-SHBG bound oestradiol in girls were -0.13 (95% confidence interval [CI] -0.14 to -0.12) and 0.005 (95% CI 0.003-0.007), respectively. The intercept and slope for non-SHBG bound testosterone in boys were -0.16 (95% CI -0.17 to -0.14) and 0.0006 (95% CI 0.0005-0.0006). Conclusion: While calculated values might be useful for research purposes, they are generally not close enough for clinical purposes.