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Measuring testosterone in women and men

      Highlights

      • Despite the advances in steroid hormone assessment, T measurements vary substantially within and across laboratories.
      • Universally accepted age- and sex-matched reference intervals for testosterone are still lacking.
      • Standardization of testosterone testing among current commercial assays should aim to improve performance at lower concentrations of testosterone.

      Abstract

      Measurement of serum testosterone (T) level is of utmost importance for the evaluation of hypogonadism in men and androgen excess in women. Despite the advances in steroid hormone assessment, substantial variability exists regarding measurement of T concentrations. Several factors affect T measurement in men, including circadian rhythms, intra-individual daily variability and transient stressors, while T concentrations in women vary mainly according to the phase of the menstrual cycle. Most of the available immunoassays lack the required accuracy when dealing with T concentrations at the lower end of the normal range for men and across the entire range for females. Consequently, there is no universally accepted lower T threshold for healthy adult men and most immunoassays fail to detect states of mild androgen excess in women. Mass spectrometry is considered the gold-standard method for T measurement; however, due to its complexity and cost, it has not been widely adopted. To increase accuracy, T in men should be measured with a fasting morning sample and repeated if the level is found to be low; in women, measurement must be performed at the follicular phase of the cycle. In both cases, borderline results may be clarified by the assessment of free testosterone (fT). Since most fT assays are unreliable, calculated surrogates should be used instead. Collaborative efforts have been undertaken, with rigorous internal and external quality controls and the establishment of reference methods, to harmonise the commercial assays.

      Keywords

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      References

        • Rosner W.
        • Auchus R.J.
        • Azziz R.
        • Sluss P.M.
        • Raff H.
        Position statement: utility, limitations, and pitfalls in measuring testosterone: an endocrine society position statement.
        J. Clin. Endocrinol. Metab. 2007; 92: 405-413https://doi.org/10.1210/jc.2006-1864
        • Labrie F.
        • Luu-The V.
        • Labrie C.
        • Bélanger A.
        • Simard J.
        • Lin S.-X.
        • Pelletier G.
        Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone.
        Endocr. Rev. 2003; 24: 152-182https://doi.org/10.1210/er.2001-0031
        • Matsumoto A.
        • Bremner W.
        • Hypogonadism Male
        Melmed S. Polonsky K. Larsen P. Kroneneberg H. Williams Textb. Endocrinol. 12th ed. Saunders, Philadelphia2011: 709-755
        • Korkidakis A.K.
        • Reid R.L.
        Testosterone in women: measurement and therapeutic use.
        J. Obstet. Gynaecol. Can. 2017; 39: 124-130https://doi.org/10.1016/j.jogc.2017.01.006
        • Wang C.
        • Nieschlag E.
        • Swerdloff R.
        • Behre H.M.
        • Hellstrom W.J.
        • Gooren L.J.
        • Kaufman J.M.
        • Legros J.J.
        • Lunenfeld B.
        • Morales A.
        • Morley J.E.
        • Schulman C.
        • Thompson I.M.
        • Weidner W.
        • Wu F.C.W.
        Investigation, treatment and monitoring of late-onset hypogonadism in males.
        Int. J. Androl. 2009; 32: 1-10https://doi.org/10.1111/j.1365-2605.2008.00924.x
        • Bhasin S.
        • Cunningham G.R.
        • Hayes F.J.
        • Matsumoto A.M.
        • Snyder P.J.
        • Swerdloff R.S.
        • Montori V.M.
        • E.S. Task Force
        Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline.
        J. Clin. Endocrinol. Metab. 2018; 103: 1-30https://doi.org/10.1210/jc.2009-2354\r10.1210/jc.2009-2354
        • Travison T.G.
        • Vesper H.W.
        • Orwoll E.
        • Wu F.
        • Kaufman J.M.
        • Wang Y.
        • Lapauw B.
        • Fiers T.
        • Matsumoto A.M.
        • Bhasin S.
        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: 1161-1173https://doi.org/10.1210/jc.2016-2935
        • Plymate S.R.
        • Tenover J.S.
        • Bremner W.J.
        Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men.
        J. Androl. 2019; 10 (n.d.): 366-371
        • Lehtihet M.
        • Arver S.
        • Bartuseviciene I.
        • Pousette A.
        S-testosterone decrease after a mixed meal in healthy men independent of SHBG and gonadotrophin levels.
        Andrologia. 2012; 44: 405-410https://doi.org/10.1111/j.1439-0272.2012.01296.x
        • Brambilla D.J.
        • O’Donnell A.B.
        • Matsumoto A.M.
        • McKinlay J.B.
        Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men.
        Clin. Endocrinol. (Oxf.). 2007; 67: 853-862https://doi.org/10.1111/j.1365-2265.2007.02976.x
        • Muehlenbein M.P.
        • Hirschtick J.L.
        • Bonner J.Z.
        • Swartz A.M.
        Toward quantifying the usage costs of human immunity: altered metabolic rates and hormone levels during acute immune activation in men.
        Am. J. Hum. Biol. 2019; 22 (n.d.): 546-556https://doi.org/10.1002/ajhb.21045
        • Chang W.Y.
        • Knochenhauer E.S.
        • Bartolucci A.A.
        • Azziz R.
        Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical characterization of the three major clinical subgroups.
        Fertil. Steril. 2005; 83: 1717-1723https://doi.org/10.1016/j.fertnstert.2005.01.096
        • Clark R.V.
        • Wald J.A.
        • Swerdloff R.S.
        • Wang C.
        • Wu F.C.W.
        • Bowers L.D.
        • Matsumoto A.M.
        Large divergence in testosterone concentrations between men and women: frame of reference for elite athletes in sex-specific competition in sports, a narrative review.
        Clin. Endocrinol. (Oxf.). 2018; : 0-3https://doi.org/10.1111/cen.13840
        • Vesper H.
        • Wang Y.
        • Botelho J.
        Challenges and improvements in testosterone and estradiol testing.
        Asian J. Androl. 2014; https://doi.org/10.4103/1008-682X.122338
        • Stanczyk F.Z.
        • Clarke N.J.
        Advantages and challenges of mass spectrometry assays for steroid hormones.
        J. Steroid Biochem. Mol. Biol. 2010; 121: 491-495https://doi.org/10.1016/j.jsbmb.2010.05.001
        • Vesper H.W.
        • Bhasin S.
        • Wang C.
        • Tai S.S.
        • Dodge L.A.
        • Singh R.J.
        • Nelson J.
        • Ohorodnik S.
        • Clarke N.J.
        • Salameh W.A.
        • Parker C.R.
        • Razdan R.
        • Monsell E.A.
        • Myers G.L.
        Interlaboratory comparison study of serum total testosterone [corrected] measurements performed by mass spectrometry methods.
        Steroids. 2009; 74: 498-503https://doi.org/10.1016/j.steroids.2009.01.004
        • Taieb J.
        • Mathian B.
        • Millot F.
        • Patricot M.-C.
        • 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: 1381-1395
        • Huhtaniemi I.T.
        • Tajar A.
        • Lee D.M.
        • O’Neill T.W.
        • Finn J.D.
        • Bartfai G.
        • Boonen S.
        • Casanueva F.F.
        • Giwercman A.
        • Han T.S.
        • Kula K.
        • Labrie F.
        • Lean M.E.J.
        • Pendleton N.
        • Punab M.
        • Silman A.J.
        • Vanderschueren D.
        • Forti G.
        • Wu F.C.W.
        • Group E.M.A.S.
        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: 983-991https://doi.org/10.1530/EJE-11-1051
        • La’ulu S.L.
        • Kalp K.J.
        • Straseski J.A.
        How low can you go? Analytical performance of five automated testosterone immunoassays.
        Clin. Biochem. 2018; 58: 64-71https://doi.org/10.1016/j.clinbiochem.2018.05.008
        • Van Uytfanghe K.
        • Stöckl D.
        • Kaufman J.M.
        • Fiers T.
        • Ross H.A.
        • De Leenheer A.P.
        • Thienpont L.M.
        Evaluation of a candidate reference measurement procedure for serum free testosterone based on ultrafiltration and isotope dilution-gas chromatography-mass spectrometry.
        Clin. Chem. 2004; 50: 2101-2110https://doi.org/10.1373/clinchem.2004.037358
        • Teede H.J.
        • Misso M.L.
        • Costello M.F.
        • Dokras A.
        • Laven J.
        • Moran L.
        • Piltonen T.
        • Norman R.J.
        • Andersen M.
        • Azziz R.
        • Balen A.
        • Baye E.
        • Boyle J.
        • Brennan L.
        • Broekmans F.
        • Dabadghao P.
        • Devoto L.
        • Dewailly D.
        • Downes L.
        • Fauser B.
        • Franks S.
        • Garad R.M.
        • Gibson-Helm M.
        • Harrison C.
        • Hart R.
        • Hawkes R.
        • Hirschberg A.
        • Hoeger K.
        • Hohmann F.
        • Hutchison S.
        • Joham A.
        • Johnson L.
        • Jordan C.
        • Kulkarni J.
        • Legro R.S.
        • Li R.
        • Lujan M.
        • Malhotra J.
        • Mansfield D.
        • Marsh K.
        • McAllister V.
        • Mocanu E.
        • Mol B.W.
        • Ng E.
        • Oberfield S.
        • Ottey S.
        • Peña A.
        • Qiao J.
        • Redman L.
        • Rodgers R.
        • Rombauts L.
        • Romualdi D.
        • Shah D.
        • Speight J.
        • Spritzer P.M.
        • Stener-Victorin E.
        • Stepto N.
        • Tapanainen J.S.
        • Tassone E.C.
        • Thangaratinam S.
        • Thondan M.
        • Tzeng C.-R.
        • van der Spuy Z.
        • Vanky E.
        • Vogiatzi M.
        • Wan A.
        • Wijeyaratne C.
        • Witchel S.
        • Woolcock J.
        • Yildiz B.O.
        Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome.
        Fertil. Steril. 2018; 110: 364-379https://doi.org/10.1016/j.fertnstert.2018.05.004
        • de Ronde W.
        • van der Schouw Y.T.
        • Pols H.A.P.
        • Gooren L.J.G.
        • Muller M.
        • Grobbee D.E.
        • de Jong F.H.
        Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms.
        Clin. Chem. 2006; 52: 1777-1784https://doi.org/10.1373/clinchem.2005.063354
        • Vermeulen A.
        Commentary: androgen replacement therapy in the aging male - a critical evaluation.
        J. Clin. Endocrinol. Metab. 2001; 86: 2380-2390https://doi.org/10.1210/jc.86.6.2380
        • Kapoor P.
        • Luttrell B.M.
        • Williams D.
        The free androgen index is not valid for adult males.
        J. Steroid Biochem. Mol. Biol. 1993; 45: 325-326
        • Rosner W.
        • Vesper H.
        Toward excellence in testosterone testing: a consensus statement.
        J. Clin. Endocrinol. Metab. 2010; 95: 4542-4548https://doi.org/10.1210/jc.2010-1314