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Clinical Manifestation and Diagnosis of Androgen Deficiency

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Book cover Endocrinology of the Testis and Male Reproduction

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

Male hypogonadism is defined as a clinical syndrome resulting from failure of the testes to produce physiological levels of testosterone and normal number of spermatozoa, due to disruption of one or more levels of the hypothalamic-pituitary-testicular axis.

The clinical and biochemical features of male hypogonadism vary according to the period of life when the gonadal failure begins and the level at which the disruption of hypothalamic-pituitary-testicular axis occurs. Whereas the fetal and prepubertal onset of androgen deficiency typically do not pose diagnostic difficulties, the identification of so-called adult- or late onset hypogonadism remains challenging. Low specificity of symptoms that are further confounded by comorbidities and aging, as well as relative inaccuracy of the assays deployed to measure testosterone level are the major factors hampering the precise diagnosis in ageing male without classical hypothalamic-pituitary-gonadal axis pathology.

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References

  • Antonio L, Wu FCW, O’Neill TW, Pye SR, Ahern TB, Laurent MR, …, Vanderschueren D. Low free testosterone is associated with hypogonadal signs and symptoms in men with normal total testosterone. J Clin Endocrinol Metab. 2007. doi:10.1210/jc.2015-4106.

    Google Scholar 

  • Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, …, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92(11):4241–7. doi:10.1210/jc.2007-1245.

    Google Scholar 

  • Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(10):3007–19. doi:10.1210/jc.2011-1137.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(6):2536–59. doi:10.1210/jc.2009-2354.

    Article  CAS  PubMed  Google Scholar 

  • Bhasin S, Pencina M, Jasuja GK, Travison TG, Coviello A, Orwoll E, …, 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(8):2430–9. doi:10.1210/jc.2010-3012.

    Google Scholar 

  • 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. 2007;67(6):853–62. doi:10.1111/j.1365-2265.2007.02976.x.

    Article  CAS  Google Scholar 

  • 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(3):907–13. doi:10.1210/jc.2008-1902.

    Article  CAS  PubMed  Google Scholar 

  • Braunstein GD. Clinical practice. Gynecomastia. N Engl J Med. 2007;357(12):1229–37. doi:10.1056/NEJMcp070677.

    Article  CAS  PubMed  Google Scholar 

  • 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. 2013;78(2):291–6. doi:10.1111/j.1365-2265.2012.04486.x.

    Article  CAS  Google Scholar 

  • Citron JT, Ettinger B, Rubinoff H, Ettinger VM, Minkoff J, Hom F, …, Alloo R. Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism. J Urol. 1996;155(2):529–33. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8558653

  • Clifton S, Macdowall W, Copas A, Tanton C, Keevil B, Lee D, …, Wu F. Salivary testosterone levels and health status in c gen eral population: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). J Clin Endocrinol Metab. 2016. doi:10.1210/jc.2016-1669.

    Google Scholar 

  • 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(11):1288–99. doi:10.1001/jama.295.11.1288.

    Article  CAS  PubMed  Google Scholar 

  • Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol. 2003;58(6):710–7.

    Article  CAS  Google Scholar 

  • Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania smell identification test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984;32:489–502.

    Article  CAS  PubMed  Google Scholar 

  • Doty RL, Marcus A, Lee WW. The development of the 12-item Cross-Cultural Smell Identification Test (CC-SIT ), based upon items from the University of Pennsylvania Smell Identification Test ( UPSIT ), is described. In, 1996;106(3):353–6.

    Google Scholar 

  • Fiers T, Delanghe J, T’Sjoen G, Van Caenegem E, Wierckx K, Kaufman J-M. A critical evaluation of salivary testosterone as a method for the assessment of serum testosterone. Steroids. 2014;86:5–9. doi:10.1016/j.steroids.2014.04.013.

    Article  CAS  PubMed  Google Scholar 

  • Goncharov N, Katsya G, Dobracheva A, Nizhnik A, Kolesnikova G, Herbst V, Westermann J. Diagnostic significance of free salivary testosterone measurement using a direct luminescence immunoassay in healthy men and in patients with disorders of androgenic status. Aging Male. 2009. Retrieved from http://www.tandfonline.com/doi/abs/10.1080/13685530600713060?journalCode=itam20

  • Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, McKinlay JB. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab. 2008;93(10):3870–7. doi:10.1210/jc.2008-0021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, …, Willnow TE. Role of endocytosis in cellular uptake of sex steroids. Cell. 2005;122(5):751–62. doi:10.1016/j.cell.2005.06.032.

    Google Scholar 

  • Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86(2):724–31. doi:10.1210/jcem.86.2.7219.

    Article  CAS  PubMed  Google Scholar 

  • Hirsch D, Benbassat C, Toledano Y, S’chigol I, Tsvetov G, Shraga-Slutzky I, …, Shimon I. Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism. Pituitary. 2015;18(4):494–9. doi:10.1007/s11102-014-0601-x.

    Google Scholar 

  • Joshi D, van Schoor NM, de Ronde W, Schaap LA, Comijs HC, Beekman ATF, Lips P. Low free testosterone levels are associated with prevalence and incidence of depressive symptoms in older men. Clin Endocrinol. 2010;72(2):232–40. doi:10.1111/j.1365-2265.2009.03641.x.

    Article  CAS  Google Scholar 

  • Keevil BG et al. Distribution of salivary testosterone in men and women in a British general population-based sample: the third national survey of sexual attitudes and lifestyles (Natsal-3). Journal of the Endocrine Society. 2017;1(1):14–25. doi:10.1210/js.2016-1029.

    Google Scholar 

  • Kim W, Rosen MA, Langer JE, Banner MP, Siegelman ES, Ramchandani P. US MR imaging correlation in pathologic conditions of the scrotum. Radiographics: Rev Publ Radiol Soc N Am, Inc. 2007;27(5):1239–53. doi:10.1148/rg.275065172.

    Article  Google Scholar 

  • Kushnir MM, Rockwood AL, Roberts WL, Yue B, Bergquist J, Meikle AW. Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories. Clin Biochem. 2011;44(1):77–88. doi:10.1016/j.clinbiochem.2010.07.008.

    Article  CAS  PubMed  Google Scholar 

  • Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75. doi:10.1210/jc.2007-1792.

    Article  CAS  PubMed  Google Scholar 

  • Licea-Perez H, Wang S, Szapacs ME, Yang E. Development of a highly sensitive and selective UPLC/MS/MS method for the simultaneous determination of testosterone and 5alpha-dihydrotestosterone in human serum to support testosterone replacement therapy for hypogonadism. Steroids. 2008;73(6):601–10. doi:10.1016/j.steroids.2008.01.018.

    Article  CAS  PubMed  Google Scholar 

  • Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, Handelsman DJ. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol. 2010;73(3):382–8. doi:10.1111/j.1365-2265.2010.03804.x.

    Article  CAS  Google Scholar 

  • Morley JE, Perry HM, Patrick P, Dollbaum CM, Kells JM. Validation of salivary testosterone as a screening test for male hypogonadism. Aging Male: Off J Int Soc Study Aging Male. 2006;9(3):165–9. doi:10.1080/13685530600907993.

    Article  CAS  Google Scholar 

  • Nanjee MN, Wheeler MJ. Plasma free testosterone – is an index sufficient? Ann Clin Biochem. 1985;22(Pt 4):387–90.

    Article  PubMed  Google Scholar 

  • Pye SR, Huhtaniemi IT, Finn JD, Lee DM, O’Neill TW, Tajar A, …, Wu FCW. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014;99(4):1357–66. doi:10.1210/jc.2013-2052.

    Google Scholar 

  • Rosner W, Vesper H. Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab. 2010;95(10):4542–8. doi:10.1210/jc.2010-1314.

    Article  CAS  PubMed  Google Scholar 

  • 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(2):405–13. doi:10.1210/jc.2006-1864.

    Article  CAS  PubMed  Google Scholar 

  • Salameh WA, Redor-Goldman MM, Clarke NJ, Reitz RE, Caulfield MP. Validation of a total testosterone assay using high-turbulence liquid chromatography tandem mass spectrometry: total and free testosterone reference ranges. Steroids. 2010;75(2):169–75. doi:10.1016/j.steroids.2009.11.004.

    Article  CAS  PubMed  Google Scholar 

  • Sartorius G, Ly LP, Sikaris K, McLachlan R, Handelsman DJ. Predictive accuracy and sources of variability in calculated free testosterone estimates. Ann Clin Biochem. 2009;46(Pt 2):137–43.

    Article  CAS  PubMed  Google Scholar 

  • Schaap LA, Pluijm SMF, Smit JH, van Schoor NM, Visser M, Gooren LJG, Lips P. The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol. 2005;63(2):152–60. doi:10.1111/j.1365-2265.2005.02315.x.

    Article  CAS  Google Scholar 

  • Shiraishi S, Lee PWN, Leung A, Goh VHH, Swerdloff RS, Wang C. Simultaneous measurement of serum testosterone and dihydrotestosterone by liquid chromatography-tandem mass spectrometry. Clin Chem. 2008;54(11):1855–63. doi:10.1373/clinchem.2008.103846.

    Article  CAS  PubMed  Google Scholar 

  • Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psychiatry. 2009;70(7):1009–16. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19653976

  • Södergård R, Bäckström 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(6):801–10.

    Article  PubMed  Google Scholar 

  • Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MDL, Adams JE, Oldham JA, Wu FCW. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95(2):639–50. doi:10.1210/jc.2009-1251.

    Article  CAS  PubMed  Google Scholar 

  • Stanczyk FZ, Clarke NJ. Advantages and challenges of mass spectrometry assays for steroid hormones. J Steroid Biochem Mol Biol. 2010;121(3–5):491–5. doi:10.1016/j.jsbmb.2010.05.001.

    Article  CAS  PubMed  Google Scholar 

  • Strong K, Wald N, Miller A, Alwan A. Current concepts in screening for noncommunicable disease: World Health Organization Consultation Group Report on methodology of noncommunicable disease screening. J Med Screen. 2005;12(1):12–9. doi:10.1258/0969141053279086.

    Article  CAS  PubMed  Google Scholar 

  • Tajar A, Forti G, O’Neill TW, Lee DM, Silman AJ, Finn JD, …, Wu FCW. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810–8. doi:10.1210/jc.2009-1796.

    Google Scholar 

  • Taylor AE, Keevil B, Huhtaniemi IT. Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow. Eur J Endocrinol. 2015;173(2):D1–12. doi:10.1530/EJE-15-0338.

    Article  CAS  PubMed  Google Scholar 

  • Thomas G. Travison, Hubert W. Vesper, Eric Orwoll, Frederick Wu, Jean Marc Kaufman, Ying Wang, Bruno Lapauw, Tom Fiers, Alvin M. Matsumoto, Shalender Bhasin; Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metab. 2017;102(4):1161–1173. doi:10.1210/jc.2016-2935.

    Google Scholar 

  • Vermeulen A, Stoïca T, Verdonck L. The apparent free testosterone concentration, an index of androgenicity. J Clin Endocrinol Metab. 1971;33(5):759–67. doi:10.1210/jcem-33-5-759.

    Article  CAS  PubMed  Google Scholar 

  • Vesper HW, Botelho JC, Wang Y. Challenges and improvements in testosterone and estradiol testing. Asian J Androl. 2014;16(2):178–84. doi:10.4103/1008-682X.122338.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vining RF, McGinley RA. The measurement of hormones in saliva: possibilities and pitfalls. J Steroid Biochem. 1987;27(1–3):81–94. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/3320544

  • Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, …, Wu FCW. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol/Eur Fed Endoc Soc. 2008;159(5):507–14. doi:10.1530/EJE-08-0601.

    Google Scholar 

  • Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(6):1802–22. doi:10.1210/jc.2011-3045.

    Article  CAS  PubMed  Google Scholar 

  • Wu FCW, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, …, Huhtaniemi IT. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35. doi:10.1056/NEJMoa0911101.

    Google Scholar 

  • Zakharov MN, Bhasin S, Travison TG, Xue R, Ulloor J, Vasan RS, …, Jasuja R. A multi-step, dynamic allosteric model of testosterone’s binding to sex hormone binding globulin. Mol Cell Endocrinol. 2015;399:190–200. doi:10.1016/j.mce.2014.09.001.

    Google Scholar 

  • Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab. 2006;91(11):4335–43. doi:10.1210/jc.2006-0401.

    Article  CAS  PubMed  Google Scholar 

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Swiecicka, A., Wu, F. (2017). Clinical Manifestation and Diagnosis of Androgen Deficiency. In: Simoni, M., Huhtaniemi, I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-29456-8_23-1

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