Total Testosterone Reference Range

Discussion in 'Men's Health Forum' started by Michael Scally MD, Oct 9, 2014.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine


    Our dataset (n = 10,098) of observed total testosterone for ages 3–88 years, split into normative ranges determined by mean predicted values (blue line) and one (red), two (blue), three (green), and four (purple) standard deviations higher and lower than the predicted values.

    Normative ranges for the model of total testosterone from ages 3–88 years. In the average case (red line) total testosterone remains constant for age >40. However, the variance in normative ranges increases for these ages, with 1st to 99th centile ranges of 5.6–27.6 nmol/L at age 35 years and 4.1–33.1 nmol/L at age 88 years.

    Kelsey TW, Li LQ, Mitchell RT, Whelan A, Anderson RA, Wallace WH. A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years. PLoS One 2014;9(10):e109346.

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages.

    However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men.

    In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men.

    We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age.

    However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years.

    This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.
    Millard Baker likes this.
  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Montagna G, Balestra S, D'Aurizio F, et al. Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry. Clinical chemistry and laboratory medicine 2018.

    Background: The total testosterone (T) cutoffs clinically adopted to define late-onset hypogonadism (LOH) do not consider the differences that exist between different analytical platforms, nor do they consider the body mass index (BMI) or age of the patient. We aimed at providing method, age and BMI-specific normal values for total T in European healthy men.

    Methods: A total of 351 eugonadal healthy men were recruited, and total T was measured with four automated immunometric assays (IMAs): ARCHITECT i1000SR (Abbott), UniCel DxI800 (Beckman Coulter), Cobas e601 (Roche), IMMULITE 2000 (Siemens) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reference ranges (RRs) were calculated for each method.

    Results: Passing and Bablok regression analysis and Bland-Altman plot showed an acceptable agreement between Abbott and LC-MS/MS, but a poor one between LC-MS/MS and the other IMAs.

    Age-specific T concentrations in non-obese (BMI <29.9 kg/m2) men were greater than in all men. The total T normal range, in non-obese men aged 18–39 years, measured with LC-MS/MS was 9.038–41.310 nmol/L.

    RRs calculated with LC-MS/MS statistically differed from the ones calculated with all individual IMAs, except Abbott and among all IMAs. Statistically significant differences for both upper and lower reference limits between our RRs and the ones provided by the manufacturers were also noticed.

    Conclusions: We calculated normal ranges in a non-obese cohort of European men, aged 18–39 years, with four commercially available IMAs and LC-MS/MS and found statistically significant differences according to the analytical method used. Method-specific reference values can increase the accuracy of LOH diagnosis and should be standardly used.
    Millard Baker likes this.