Laboratory Measurement of Testosterone

Abstract

Plasma testosterone concentrations in men, first quantified nearly half a century ago, are now measured routinely as a primary index of androgen status. Most clinical laboratories employ a multichannel, fully automated analyzer. Current evidence suggests that these analyzers are capable of satisfactorily quantifying the concentration of total plasma testosterone in men. Newer technology, in the form of tandem mass spectrometry, may, in the future, replace these automated platforms, providing a more specific estimate of testosterone concentration. When concentrations of plasma testosterone are found to be around the lower limit of normal ( 9.0 nmol/l; microg/l=nmol/lx0.288), some measure of bioactive testosterone should be sought. This may be a free (non-protein-bound) or bioavailable (free plus albumin-bound) testosterone and may be measured (laborious and time-consuming and therefore unsuited to routine clinical laboratories) or calculated using any one of a variety of mathematical expressions. Sampling for the estimation of plasma testosterone should be carried out in the morning, before 11:00 h, to obviate the effect of the marked diurnal variation in testosterone production. In samples found to have an equivocal concentration (7.0-12.5 nmol/l) at least one more estimate should be obtained to account for the possible significant intra-individual variability. Although it is generally accepted that the concentrations of total, free and bioavailable testosterone decline as men age, the majority of elderly men have testosterone levels in the young adult range (9.0-35 nmol/l) and some maintain a diurnal rhythm. Salivary testosterone offers a non-invasive estimate of free testosterone but there does not appear to be an immediate demand for a routine salivary testosterone service.

A cross-sectional study of the association of age, race and ethnicity, and body mass index with sex steroid hormone marker profiles among men in the National Health and Nutrition Examination Survey (NHANES III)

“…Previous studies have suggested that lowered T and E metabolism, and increasing SHBG levels were associated with older ages 19 22 26 36–39 54. This was in agreement with our results, since 74% of men are over 50 years in this profile, and associations were strongest with older age groups (table 3).…”

Higher serum testosterone is associated with increased risk of advanced hepatitis C–related liver disease in males

“…However, total testosterone correlates well with free testosterone in aging males,39 has been shown to be reliably associated with increased risk of diabetes,38 and has been shown to be a more valid predictor of androgen deficiency function than either directly measured free testosterone or calculated bioavailable testosterone 39. Total testosterone is also much more widely accessible and more reliably measured than is directly measured free testosterone 40. Finally, because of sample‐size constraints, we were able to perform only an exploratory evaluation of interaction between total testosterone and other risk factors of interest, including age and adiposity.…”

Pathogenesis And Symptomology Of The Exercise-hypogonodal Male Condition

“…Once testosterone is in circulation it can be loosely bound to albumin (~20-30%), tightly bound to sex hormone binding globulin (SHBG) (~50-70%), bound to other proteins (~4%) or unbound, known as 'free' (~1-3%) (18). Traditionally, free testosterone has been thought of as the only form of testosterone that is biologically available, often referred to as the "free hormone hypothesis" (56).…”