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Testosterone pp 97–107Cite as

Utility and Limitations in Measuring Testosterone

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Abstract

In men, testosterone, the principal circulating androgen, has essential reproductive functions in establishing and maintaining the male phenotype. It also plays important anabolic roles in somatic tissues, such as muscle and bone. Organic hypogonadism resulting from structural hypothalamic-pituitary testicular (HPT) axis dysfunction is an important diagnosis not to be missed. It is an important differential to consider not only in the man presenting with low libido or infertility, but also with non-reproductive features such as otherwise unexplained weakness, anemia or osteoporosis. Hypogonadism is primarily a clinical diagnosis. Men who present with features suggestive of androgen deficiency should undergo a thorough history and physical examination to determine the degree of clinically significant androgen deficiency. Verification of the clinical impression by confirming low testosterone levels is an essential component of the diagnosis. Accordingly, the Endocrine Society recommends making a diagnosis of androgen deficiency only in men with consistent symptoms and signs as well as unequivocally and repeatedly low serum testosterone levels [1]. While the diagnosis is relatively straightforward in young otherwise healthy men, it considered more difficult in older, obese men with comorbidities. Even low libido, the most specific sexual symptoms can be caused by many other conditions such as vascular disease or depression, and the physical examination can be nonspecific. In the European Male Ageing Study, where the prevalence of sexual symptoms ranged from 27.5 % to 39.9 % in community-dwelling men, yet only 2.1 % met the definition of late onset hypogonadism, i.e. the syndromic combination of symptoms with low testosterone [2]. Given this non-specificity of clinical features in the absence of a biological gold standard of male hypogonadism akin to cessation of menses in females, accurate biochemical confirmation is important. This can be fraught with difficulties and pitfalls, and will be discussed in this chapter. This chapter will focus on testosterone measurements in adult men. Measurements of other reproductive steroids and further work-up of low testosterone is beyond the scope of this contribution.

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References

  1. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59.

    Article  CAS  PubMed  Google Scholar 

  2. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123–35.

    Article  CAS  PubMed  Google Scholar 

  3. Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clin Endocrinol (Oxf). 2015;83:344.

    Article  CAS  PubMed  Google Scholar 

  4. Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Veldhuis JD, King JC, Urban RJ, Rogol AD, Evans WS, Kolp LA, Johnson ML. Operating characteristics of the male hypothalamo-pituitary-gonadal axis: pulsatile release of testosterone and follicle-stimulating hormone and their temporal coupling with luteinizing hormone. J Clin Endocrinol Metab. 1987;65:929–41.

    Article  CAS  PubMed  Google Scholar 

  6. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983;56:1278–81.

    Article  CAS  PubMed  Google Scholar 

  7. Brambilla DJ, Matsumoto AM, Araujo AB, McKinlay JB. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94:907–13.

    Article  CAS  PubMed  Google Scholar 

  8. Caronia LM, Dwyer AA, Hayden D, Amati F, Pitteloud N, Hayes FJ. Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism. Clin Endocrinol (Oxf). 2013;78:291–6.

    Article  CAS  PubMed  Google Scholar 

  9. Sartorius G, Spasevska S, Idan A, Turner L, Forbes E, Zamojska A, Allan CA, Ly LP, Conway AJ, McLachlan RI, Handelsman DJ. Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study. Clin Endocrinol (Oxf). 2012;77:755–63.

    Article  CAS  PubMed  Google Scholar 

  10. Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf). 2007;67:853–62.

    Article  CAS  PubMed  Google Scholar 

  11. Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, Macisaac RJ, Clarke S, Zajac JD, Jerums G. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab. 2008;93:1834–40.

    Article  CAS  PubMed  Google Scholar 

  12. Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab. 2000;85:4500–10.

    CAS  PubMed  Google Scholar 

  13. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005;90:678–88.

    Article  CAS  PubMed  Google Scholar 

  14. Kelleher S, Conway AJ, Handelsman DJ. Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metab. 2004;89:3813–7.

    Article  CAS  PubMed  Google Scholar 

  15. Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab. 2004;6:208–15.

    Article  CAS  PubMed  Google Scholar 

  16. Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab. 2011;96:2341–53.

    Article  CAS  PubMed  Google Scholar 

  17. Travison TG, Araujo AB, Kupelian V, O’Donnell AB, McKinlay JB. The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab. 2007;92:549–55.

    Article  CAS  PubMed  Google Scholar 

  18. Grossmann M, Anawalt BD, Wu FC. Clinical practice patterns in the assessment and management of low testosterone in men: an international survey of endocrinologists. Clin Endocrinol (Oxf). 2015;82:234–41.

    Article  CAS  PubMed  Google Scholar 

  19. Rosner W. Sex steroids and the free hormone hypothesis. Cell. 2006;124:455–6. author reply 456-457.

    Article  CAS  PubMed  Google Scholar 

  20. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295:1288–99.

    Article  CAS  PubMed  Google Scholar 

  21. Vos MJ, Mijnhout GS, Rondeel JM, Baron W, Groeneveld PH. Sex hormone binding globulin deficiency due to a homozygous missense mutation. J Clin Endocrinol Metab. 2014;99:E1798–802.

    Article  CAS  PubMed  Google Scholar 

  22. Wierman ME, Auchus RJ, Haisenleder DJ, Hall JE, Handelsman D, Hankinson S, Rosner W, Singh RJ, Sluss PM, Stanczyk FZ. Editorial: the new instructions to authors for the reporting of steroid hormone measurements. J Clin Endocrinol Metab. 2014;99:4375.

    Article  CAS  PubMed  Google Scholar 

  23. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92:405–13.

    Article  CAS  PubMed  Google Scholar 

  24. Ketha H, Kaur S, Grebe SK, Singh RJ. Clinical applications of LC-MS sex steroid assays: evolution of methodologies in the 21st century. Curr Opin Endocrinol Diabetes Obes. 2014;21:217–26.

    Article  CAS  PubMed  Google Scholar 

  25. Vesper HW, Botelho JC, Wang Y. Challenges and improvements in testosterone and estradiol testing. Asian J Androl. 2014;16:178–84.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Middle JG. Dehydroepiandrostenedione sulphate interferes in many direct immunoassays for testosterone. Ann Clin Biochem. 2007;44:173–7.

    Article  CAS  PubMed  Google Scholar 

  27. Taylor AE, Keevil B, Huhtaniemi I. Mass spectrometry and immunoassay; how to measure steroid hormones today and tomorrow. Eur J Endocrinol. 2015;173:D1.

    Article  CAS  PubMed  Google Scholar 

  28. Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N, Lacroix I, Somma-Delpero C, Boudou P. Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography-mass spectrometry in sera from 116 men, women, and children. Clin Chem. 2003;49:1381–95.

    Article  CAS  PubMed  Google Scholar 

  29. Wang C, Catlin DH, Demers LM, Starcevic B, Swerdloff RS. Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab. 2004;89:534–43.

    Article  CAS  PubMed  Google Scholar 

  30. Sikaris K, McLachlan RI, Kazlauskas R, de Kretser D, Holden CA, Handelsman DJ. Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. J Clin Endocrinol Metab. 2005;90:5928–36.

    Article  CAS  PubMed  Google Scholar 

  31. Huhtaniemi IT, Tajar A, Lee DM, O’Neill TW, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Forti G, Wu FC. Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men. Eur J Endocrinol. 2012;166:983–91.

    Article  CAS  PubMed  Google Scholar 

  32. Vesper HW, Bhasin S, Wang C, Tai SS, Dodge LA, Singh RJ, Nelson J, Ohorodnik S, Clarke NJ, Salameh WA, Parker Jr CR, Razdan R, Monsell EA, Myers GL. Interlaboratory comparison study of serum total testosterone [corrected] measurements performed by mass spectrometry methods. Steroids. 2009;74:498–503.

    Article  CAS  PubMed  Google Scholar 

  33. Sodergard R, Backstrom T, Shanbhag V, Carstensen H. Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem. 1982;16:801–10.

    Article  CAS  PubMed  Google Scholar 

  34. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84:3666–72.

    Article  CAS  PubMed  Google Scholar 

  35. Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, Handelsman DJ. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf). 2010;73:382–8.

    Article  CAS  PubMed  Google Scholar 

  36. Raivio T, Palvimo JJ, Dunkel L, Wickman S, Janne OA. Novel assay for determination of androgen bioactivity in human serum. J Clin Endocrinol Metab. 2001;86:1539–44.

    CAS  PubMed  Google Scholar 

  37. Jarow JP, Troiani J, McNellis D, Wiederhorn R, Fang G, Handelsman H. Use of biomarkers to assess tissue specific androgen adequacy: defining male hypogonadism. J Urol. 2013;189:633–7.

    Article  CAS  PubMed  Google Scholar 

  38. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30:1–9.

    Article  PubMed  Google Scholar 

  39. Bhasin S, Pencina M, Jasuja GK, Travison TG, Coviello A, Orwoll E, Wang PY, Nielson C, Wu F, Tajar A, Labrie F, Vesper H, Zhang A, Ulloor J, Singh R, D’Agostino R, Vasan RS. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. J Clin Endocrinol Metab. 2011;96:2430–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, Hankey GJ, Norman PE, Flicker L. Reference ranges and determinants of testosterone, dihydrotestosterone, and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. J Clin Endocrinol Metab. 2012;97:4030–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine Austin Health, University of Melbourne, 145 Studley Road, Heidelberg, VIC, 3052, Australia

    Mathis Grossmann

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  1. Brazilian Society of Endocrinology and Metabolism (SBEM), Humaitá, Rio de Janeiro, Brazil

    Alexandre Hohl

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Grossmann, M. (2017). Utility and Limitations in Measuring Testosterone. In: Hohl, A. (eds) Testosterone. Springer, Cham. https://doi.org/10.1007/978-3-319-46086-4_4

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  • DOI: https://doi.org/10.1007/978-3-319-46086-4_4

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