The analog free testosterone assay: are the results in men clinically useful?
Abstract
Men with low testosterone concentrations are usually hypogonadal. However, because variations in the testosterone transport protein, sex hormone-binding globulin (SHBG), directly influence the total testosterone concentration, confirmation of a low testosterone with a measurement of free testosterone or “bioavailable” testosterone (BAT) is recommended. In the present study, we examined the relationship of SHBG with free testosterone (Coat-A-Count assay, Diagnostic Products) and with BAT in men (n = 29) and women (n = 28) who participated in a study of the metabolic determinants of body composition. As expected, total testosterone was strongly positively correlated with SHBG among men (r = 0.68; P <0.01). Although the BAT was independent of SHBG in men (r = 0.02), SHBG was an important predictor of free testosterone (r = 0. 62; P <0.01). In contrast, in women serum concentrations of total testosterone (r = −0.26; P = 0.17), free testosterone (r = −0.30; P = 0.17), and BAT (r = −0.46; P = 0.013) all tended to be lower with increasing SHBG. Free testosterone was nearly perfectly positively correlated with total testosterone (r = 0.97) in men, among whom free testosterone represented a relatively constant percentage of the total testosterone (0.5–0.65%), and the percentage of free testosterone was unrelated to SHBG. Thus the Coat-A-Count free testosterone concentration in men, like the total testosterone concentration, is determined in part by plasma SHBG. Accordingly, androgen deficiency may be misclassified with this assay in men with low SHBG. Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related.
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Analog-based immunoassays do not detect nor quantify free T.
“Comparative studies of this analog-based immunoassay and ED confirmed that this technique does not detect nor quantify free T and that is should, therefore, not be used as an assay for free T [205, 207, 208].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [207]
Cites
Vermeulen, A. (1996) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.81.5.1821 · Cited by 455 · see citing works
Haffner, S. M., Shaten, J., Stem, M. P., Smith, G. D., Kuller, L., & MRFIT Research Group (1996) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a008832 · Cited by 320 · see citing works
Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension
Phillips, G. B., Jing, T.-Y., Resnick, L. M., Barbagallo, M., Laragh, J. H., & Sealey, J. E. (1993) · Journal of Hypertension · doi:10.1097/00004872-199307000-00003 · Cited by 117 · cited 2× · see citing works
“Others (14, 15) have noted that free testosterone measured by the Coat-A-Count assay is influenced by the concentration of SHBG; however, the potential importance of this relationship was not emphasized.”
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A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824 · see citing works
Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes
Dhindsa, S., Prabhakar, S., Sethi, M., Bandyopadhyay, A., Chaudhuri, A., & Dandona, P. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0804 · Cited by 631 · see citing works
Andropause: clinical implications of the decline in serum testosterone levels with aging in men
Matsumoto, A. M. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.2.m76 · Cited by 490 · see citing works
A Reappraisal of Testosterone’s Binding in Circulation: Physiological and Clinical Implications
Goldman, A. L., Bhasin, S., Wu, F. C. W., Krishna, M., Matsumoto, A. M., & Jasuja, R. (2017) · Endocrine Reviews · doi:10.1210/er.2017-00025 · Cited by 414 · see citing works
Evaluation of assays available to measure free testosterone
Morley, J. E., Patrick, P., & Perry, H. M. (2002) · Metabolism · doi:10.1053/meta.2002.31975 · Cited by 309 · see citing works
Association of Bioavailable, Free, and Total Testosterone With Insulin Resistance
Tsai, E. C., Matsumoto, A. M., Fujimoto, W. Y., & Boyko, E. J. (2004) · Diabetes Care · doi:10.2337/diacare.27.4.861 · Cited by 307 · see citing works
Miller, K. K., Rosner, W., Lee, H., Hier, J., Sesmilo, G., Schoenfeld, D., Neubauer, G., & Klibanski, A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030680 · Cited by 301 · see citing works
Predictive accuracy and sources of variability in calculated free testosterone estimates
Sartorius, G., Ly, L. P., Sikaris, K., McLachlan, R., & Handelsman, D. J. (2009) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1258/acb.2008.008171 · Cited by 175 · see citing works
Morris, P., Malkin, C., Channer, K., & Jones, T. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1510241 · Cited by 122 · see citing works
Narinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96 · see citing works
Bhasin, S., Zhang, A., Coviello, A., Jasuja, R., Ulloor, J., Singh, R., Vesper, H., & Vasan, R. S. (2008) · Steroids · doi:10.1016/j.steroids.2008.07.003 · Cited by 79 · see citing works
Juul, A. (2002) · Human Reproduction Update · doi:10.1093/humupd/8.5.423 · Cited by 80 · see citing works
Testosterone concentrations in young pubertal and post-pubertal obese males
Mogri, M., Dhindsa, S., Quattrin, T., Ghanim, H., & Dandona, P. (2013) · Clinical Endocrinology · doi:10.1111/cen.12018 · Cited by 79 · see citing works
Endogenous plasma testosterone levels and commission errors in women: a preliminary report
BJORK, J., MOELLER, F., DOUGHERTY, D., & SWANN, A. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(01)00474-7 · Cited by 38 · see citing works
- Authors
- Winters, S. J., Kelley, D. E., & Goodpaster, B.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Winters, Stephen J
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-10-01
- Volume
- 44
- Issue
- 10
- Pages
- 2178-2182
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2103054709
- Cited by
- 160
- References
- 3
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd019546-14)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-49200, R01DK049200)
- National Center for Research Resources (M01RR000056, 5 M01 RR00056)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 19546)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- free testosterone, sex hormone-binding globulin, bioavailable testosterone, hypogonadism, androgen deficiency, total testosterone, sex differences, hyperinsulinemia, hypertension, type 2 diabetes risk
- MeSH terms
- Adult, Body Composition, Female, Humans, Male, Middle Aged, Obesity, Protein Binding, Reagent Kits, Diagnostic, Sex Hormone-Binding Globulin, Testosterone
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