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Endocrinology and Metabolism |
a Address correspondence to this author at: Department of Medicine, University of Pittsburgh Medical Center, Montefiore-N919, 200 Lothrop Street, Pittsburgh, PA 15213. Fax 412-692-4019; e-mail Winters{at}med1.dept-med.pitt.edu.
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.
The following articles in journals at HighWire Press have cited this article:
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  R. S. Swerdloff and C. Wang Free Testosterone Measurement by the Analog Displacement Direct Assay: Old Concerns and New Evidence Clin. Chem., March 1, 2008; 54(3): 458 - 460. [Full Text] [PDF]
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K. S. Fritz, A. J.S. McKean, J. C. Nelson, and R. B. Wilcox Analog-Based Free Testosterone Test Results Linked to Total Testosterone Concentrations, Not Free Testosterone Concentrations Clin. Chem., March 1, 2008; 54(3): 512 - 516. [Abstract] [Full Text] [PDF]
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 L. Katznelson, M. W Robinson, C. L Coyle, H. Lee, and C. E Farrell Effects of modest testosterone supplementation and exercise for 12 weeks on body composition and quality of life in elderly men Eur. J. Endocrinol., December 1, 2006; 155(6): 867 - 875. [Abstract] [Full Text] [PDF]
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 S. Basaria and A. S. Dobs Controversies Regarding Transdermal Androgen Therapy in Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4743 - 4752. [Abstract] [Full Text] [PDF]
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F. Giton, J. Fiet, J. Guechot, F. Ibrahim, F. Bronsard, D. Chopin, and J.-P. Raynaud Serum Bioavailable Testosterone: Assayed or Calculated? Clin. Chem., March 1, 2006; 52(3): 474 - 481. [Abstract] [Full Text] [PDF]
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S. Bhasin Female Androgen Deficiency Syndrome--An Unproven Hypothesis J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4970 - 4972. [Full Text] [PDF]
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L. P Ly and D. J Handelsman Empirical estimation of free testosterone from testosterone and sex hormone-binding globulin immunoassays Eur. J. Endocrinol., March 1, 2005; 152(3): 471 - 478. [Abstract] [Full Text] [PDF]
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S. Dhindsa, S. Prabhakar, M. Sethi, A. Bandyopadhyay, A. Chaudhuri, and P. Dandona Frequent Occurrence of Hypogonadotropic Hypogonadism in Type 2 Diabetes J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5462 - 5468. [Abstract] [Full Text] [PDF]
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K. Van Uytfanghe, D. Stockl, J. M. Kaufman, T. Fiers, H. A. Ross, A. P. De Leenheer, and L. M. Thienpont Evaluation of a Candidate Reference Measurement Procedure for Serum Free Testosterone Based on Ultrafiltration and Isotope Dilution-Gas Chromatography-Mass Spectrometry Clin. Chem., November 1, 2004; 50(11): 2101 - 2110. [Abstract] [Full Text] [PDF]
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 E. C. Tsai, A. M. Matsumoto, W. Y. Fujimoto, and E. J. Boyko Association of Bioavailable, Free, and Total Testosterone With Insulin Resistance: Influence of sex hormone-binding globulin and body fat Diabetes Care, April 1, 2004; 27(4): 861 - 868. [Abstract] [Full Text] [PDF]
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K. K. Miller, W. Rosner, H. Lee, J. Hier, G. Sesmilo, D. Schoenfeld, G. Neubauer, and A. Klibanski Measurement of Free Testosterone in Normal Women and Women with Androgen Deficiency: Comparison of Methods J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 525 - 533. [Abstract] [Full Text] [PDF]
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M. Muller, Y. T. van der Schouw, J. H. H. Thijssen, and D. E. Grobbee Endogenous Sex Hormones and Cardiovascular Disease in Men J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5076 - 5086. [Abstract] [Full Text] [PDF]
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 P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]
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 G. A. Brown, M. D. Vukovich, E. R. Martini, M. L. Kohut, W. D. Franke, D. A. Jackson, and D. S. King Endocrine and Lipid Responses to Chronic Androstenediol-Herbal Supplementation in 30 to 58 Year Old Men J. Am. Coll. Nutr., October 1, 2002; 20(5): 520 - 528. [Abstract] [Full Text] [PDF]
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 A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]
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R. Davies, C. Collier, M. Raymond, J. Heaton, and A. Clark Indirect Measurement of Bioavailable Testosterone with the Bayer Immuno 1 System Clin. Chem., February 1, 2002; 48(2): 388 - 390. [Full Text] [PDF]
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 G. A. Brown, E. R. Martini, B. S. Roberts, M. D. Vukovich, and D. S. King Acute hormonal response to sublingual androstenediol intake in young men J Appl Physiol, January 1, 2002; 92(1): 142 - 146. [Abstract] [Full Text] [PDF]
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S. Grinspoon, C. Corcoran, T. Stanley, A. Baaj, N. Basgoz, and A. Klibanski Effects of Hypogonadism and Testosterone Administration on Depression Indices in HIV-Infected Men J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 60 - 65. [Abstract] [Full Text]
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A. Vermeulen, L. Verdonck, and J. M. Kaufman A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3666 - 3672. [Abstract] [Full Text] [PDF]
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D. S. Ooi, J. G. Donnelly, S. J. Winters, D. E. Kelley, and B. Goodpaster More on the Analog Free-Testosterone Assay • The authors of the article cited above respond: Clin. Chem., May 1, 1999; 45(5): 714 - 716. [Full Text] [PDF]
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