In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values
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Dinamarie Garcia-Banigan
,
Andre Guay
Abstract
Background: Calculated free testosterone (cFT) is determined from the values of total testosterone (TT), sex hormone binding globulin (SHBG), and albumin (Alb) using mathematical formulae. We evaluated any potential cFT variance when determined with fixed Alb (4.3 g/dL) compared to measured Alb, and the point at which low SHBG and Alb combinations produced significant cFT variance.
Materials: We analyzed 2050 data points in 1222 women. cFT values with fixed vs. the actual measured Alb values were evaluated and contrasted. cFT levels were determined theoretically for all possible combinations of TT, SHBG, and Alb.
Methods: Agreement between the two measures was assessed with Lin’s concordance coefficient. Statistical analyses were performed using R software version 2.12.1.
Results: Mean Alb was 4.05±0.30 g/dL. Mean SHBG 73.0±53.3 nmol/L. A fixed Alb of 4.3 g/dL produced no significant variance for most evaluations of cFT. The accuracy decreased with Alb ≤3.5 g/dL in combination with SHBG ≤30 nmol/L and exists in 1.0% of the samples.
Conclusions: A fixed Alb of 4.3 g/dL is acceptable for most clinical evaluations. If Alb is ≤3.5 g/dL, along with SHBG ≤30 nmol/L, the variance increases and a free testosterone (FT) measurement by equilibrium dialysis is warranted for better accuracy.
Acknowledgments
This research was conducted without industry support, but rather with a generous grant from the Ellithorpe family.
References
1. Loeser A. Subcutaneous implantation of female and male hormone in tablet form in women. Br Med J 1940;1:479–82.10.1136/bmj.1.4133.479Suche in Google Scholar
2. Carter AC, Cohen CJ, Shorr E. The use of androgens in women. Vitam Horm 1947;5:317–91.10.1016/S0083-6729(08)60814-6Suche in Google Scholar
3. Greenblatt RB. Testosterone propionate pellet implantation in genetic disorders. J Am Med Assoc 1943;121:17–24.10.1001/jama.1943.02840010019004Suche in Google Scholar
4. Traish AM, Feeley RJ, Guay AT. Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938–2008. J Sex Med 2009;6:334–51.10.1111/j.1743-6109.2008.01121.xSuche in Google Scholar
5. Braunstein G, Burger H, Davis S, Dennerstein L, Goldstein I, Guay A, Leiblum S, Lobo R, Notelovitz M, Rosen R, Sarrel P, Sherwin B, Simon J, Simpson E, Spark R, Traish A. Female androgen deficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril 2002;77:660–5.10.1016/S0015-0282(02)02969-2Suche in Google Scholar
6. Traish AM, Goldstein I, Munarriz R, Guay A. Role of androgens in women’s sexual function & dysfunction: what have we learned in six decades. Curr Wom Health Rev 2006;2:75–86.10.2174/157340406775486337Suche in Google Scholar
7. Traish AM, Guay A, Feeley R, Saad F. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl 2009;30:10–22.10.2164/jandrol.108.005215Suche in Google Scholar PubMed
8. Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 2009;30:23–32.10.2164/jandrol.108.005751Suche in Google Scholar PubMed
9. Traish AM, Saad F, Feeley RJ, Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl 2009;30:477–94.10.2164/jandrol.108.007245Suche in Google Scholar PubMed
10. Travison TG, Nguyen AH, Naganathan V, Stanaway F, Blyth F, Cummings R, Le Couteur D, Sambrook P, Handelsman D. Changes in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: The Concord Health and Ageing in Men Project. J Clin Endocr 2011;96:2464–74.10.1210/jc.2011-0143Suche in Google Scholar PubMed
11. Wehr E, Pilz S, Boehm BO, Grammer T, Obermayer-Pietsch B. Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography. Eur J Heart Fail 2011;13:482–8.10.1093/eurjhf/hfr007Suche in Google Scholar
12. Lepage R. Measurement of testosterone and its sub-fractions in Canada. Clin Biochem 2006;39:97–108.10.1016/j.clinbiochem.2005.10.014Suche in Google Scholar
13. Mazer NA. A novel spreadsheet method for calculating the free serum concentrations of testosterone, dihydrotestosterone, estradiol, estrone and cortisol: with illustrative examples from male and female populations. Steroids 2009;74:512–19.10.1016/j.steroids.2009.01.008Suche in Google Scholar
14. Giton F, Urien S, Born C, Tichet J, Guechot J, Callebert J, Bronsard F, Raynaud J, Fiet J. Determination of bioavailable testosterone [non sex hormone binding globulin (SHBG)-bound testosterone] in a population of healthy French men: influence of androstenediol on testosterone binding to SHBG. Clin Chem 2007;53:160–8.10.1373/clinchem.2007.087312Suche in Google Scholar
15. Emadi-Konjin P, Bain J, Bromberg IL. Evaluation of an algorithm for calculation of serum “bioavailable” testosterone (BAT). Clin Biochem 2003;36:591–6.10.1016/S0009-9120(03)00076-6Suche in Google Scholar
16. Hackbarth J, Hoyne J, Grebe S, Singh R. Accuracy of calculated free testosterone differs between equations and depends on gender and SHBG concentration. Steroids 2011;76:48–55.10.1016/j.steroids.2010.08.008Suche in Google Scholar PubMed
17. Sinha-Hikim I, Arver S, Beall G, Shen R, Guerrero M, Sattler F, Shikuma C, Nelson J, Lardgren B, Mazer N, Bhasin S. The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women. J Clin Endo and Metab 1998;83:1312–18.10.1210/jc.83.4.1312Suche in Google Scholar
18. Wheeler MJ, Barnes SC. Measurement of testosterone in the diagnosis of hypogonadism in the ageing male. Clin Endo 2008;69:515–25.10.1111/j.1365-2265.2008.03325.xSuche in Google Scholar PubMed
19. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocr Metab 1999;84:3666–72.10.1210/jcem.84.10.6079Suche in Google Scholar PubMed
20. Miller KK, Rosner W, Lee H, Hier J, Sesmilo G, Schoenfeld D, Neubauer G, Kilbanski A. Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. J Clin Endocr Metab 2004;89:525–33.10.1210/jc.2003-030680Suche in Google Scholar PubMed
21. Moreno-Perez O, Escoin C, Serna-Candel C. Portilla J, Boix V, Alfayate R, Gonzalez-Sanchez, V, Mauri M, Sanchez-Payer J, Pico A. The determination of TT and free testosterone (RIA) is not applicable to the evaluation of gonadal function in HIV-infected males. J Sex Med 2010;7:2873–83.10.1111/j.1743-6109.2010.01886.xSuche in Google Scholar
22. Hayashi T, Yamada T. Association of bioavailable estradiol and testosterone levels with serum albumin levels in elderly men. Aging Male 2008;11:63–70.10.1080/13685530701779234Suche in Google Scholar
23. Xita N, Tsatsoulis A. Genetic variants of sex hormone-binding globulin and their biological consequences. Molec Cell Endocr 2010;316:60–5.10.1016/j.mce.2009.08.025Suche in Google Scholar
24. Ring HZ, Lessov CN, Reed T, Marcus R, Holloway L, Swan G, Carmelli D. Heritability of plasma sex hormones and hormone binding globulin in adult male twins. J Clin Endocr Metab 2005;90:3653–8.10.1210/jc.2004-1025Suche in Google Scholar
25. Stone J, Folkerd E, Doody D, Schroen C, Treloar S, Giles G, Pike M, English D, Southey M, Hooper J, Dowsett M. Familial correlations in postmenopausal serum concentrations of sex steroid hormones and other mitogens: a twins and sisters study. J Clin Endocr Metab 2009;94:4793–800.10.1210/jc.2009-0713Suche in Google Scholar
26. Vanbillemont G, Bogaert V, De Bacquer D, Lupauw B, Golmaere S, Toye K, Van Steen K, Taen Y, Kaufman J. Polymorphisms of the SHBG gene contribute to the individual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clin Endocr 2009;70:303–10.10.1111/j.1365-2265.2008.03365.xSuche in Google Scholar
27. Ahn J, Schumacher FR, Berndt SI, Pfeiffer R, Albanes D, Andriole GL, Ardanaz E, Boeing H, Bueno-de-Mesquita B, Chanock SJ, Clavel-Chapelon F, Diver WR, Feigelson HS, Gaziano JM, Giovannucci E, Haiman CA, Henderson BE, Hoover RN, Kolonel LN, Kraft P, Ma J, Le Marchand L, Overvad K, Palli D, Stattin P, Stampfer M, Stram DO, Thomas G, Thun MJ, Travis RC, Trichopoulos D, Virtamo J, Weinstein SJ, Yeager M, Kaaks R, Hunter DJ, Hayes RB. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). Hum Molec Gen 2009;18:3749–57.10.1093/hmg/ddp302Suche in Google Scholar
28. Eriksson AL, Lorentzon M, Mellström D, Vandenpat L, Swan C, Anderson N, Hammond G, Jakobsson J, Rane A, Orwoll E, Ljuggren O, Johnell O, Labrie F, Windahl S, Ohlsson C. SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. J Clin Endocr Metab 2006;91:5029–37.10.1210/jc.2006-0679Suche in Google Scholar
29. Ukkola O, Rankinen T, Gagnon J, Leon A, Skinner J, Wilmore J, Rao D, Bouchard C. A genome-wide linkage scan for steroids and SHBG levels in black and white families: the HERITAGE Family Study. J Clin Endocr Metab 2002;87:3708–20.10.1210/jcem.87.8.8725Suche in Google Scholar
30. Jaquish CE, Blangero J, Haffner SM, Stern M, MacCluer J. Quantitative genetics of serum sex hormone-binding globulin levels in participants in the San Antonio Family Heart Study. Metabolism 1997;46:988–91.10.1016/S0026-0495(97)90266-3Suche in Google Scholar
31. Guay AT, Traish AM, Hislop-Chestnut DT, Doros G, Gawoski JM. Are there variances of calculated free testosterone attributed to variations in albumin and sex hormone-binding globulin concentrations in men? Endocr Pract 2013;19:1–7.10.4158/EP12113.ORSuche in Google Scholar PubMed
32. Lin L. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989;45:255–68.10.2307/2532051Suche in Google Scholar
33. Rosner W, Vesper H, Endocrine Society, American Association for Clinical Chemistry, American Association of Clinical Endocrinologists, Androgen Excess/PCOS Society, American Society for Bone and Mineral Research, American Society for Reproductive Medicine, American Urological Association, Association of Public Health Laboratories, Endocrine Society, Laboratory Corporation of America, North American Menopause Society, Pediatric Endocrine Society. Toward excellence in testosterone testing: a consensus statement. J Clin Endocr Metab 2010;95:4542–8.10.1210/jc.2010-1314Suche in Google Scholar PubMed
34. Moreno SA, Shyam A, Morgentaler A. Comparison of free testosterone results by analog radioimmunoassay and calculated free testosterone in an ambulatory clinical population. J Sex Med 2010;7:1948–53.10.1111/j.1743-6109.2009.01473.xSuche in Google Scholar PubMed
35. Okamura K, Ando F, Shimokata H. Serum total and free testosterone level of Japanese men: a population-based study. Int J Uro 2005;12:810–4.10.1111/j.1442-2042.2005.01143.xSuche in Google Scholar PubMed
36. Davis SR, Davison SL, Donath S, Bell R. Circulating androgen levels and self-reported sexual function in women. J Am Med Assoc 2005;294:91–6.10.1001/jama.294.1.91Suche in Google Scholar PubMed
37. Guay AT, Munarriz R, Jacobson J, Talakoub L, Traish A, Quirk F, Goldstein I, Spark R. Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part A. Serum androgen levels in women aged 20–49 years with no complaints of sexual dysfunction. Int J Imp Res 2004;16;112–20.10.1038/sj.ijir.3901178Suche in Google Scholar PubMed
38. Bogaert V, Taes Y, Konings P, Van Steen K, De Baacquer D, Goemaerke S, Zmierczak H, Crabbe P, Kaufman J. Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clin Endocr 2008;69:129–35.10.1111/j.1365-2265.2008.03173.xSuche in Google Scholar PubMed
39. Wickham EP, Ewens KG, Legro RS, Duaif A, Nestler J, Strauss J. Polymorphisms in the SHBG gene influence serum SHBG levels in women with polycystic ovary syndrome. J Clin Endocr Metab 2011;96:E719–27.10.1210/jc.2010-1842Suche in Google Scholar PubMed PubMed Central
40. Ly LP, Sartorius G, Hull L, Leung A, Swerdloff R, Wang C, Handelsman D. Accuracy of calculated free testosterone formulae in men. Clin Endocr 2010;73:382–8.10.1111/j.1365-2265.2010.03804.xSuche in Google Scholar PubMed
©2014 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Letter to the Editor
-
Acute mental feelings and professional stress are controlling health. Mechanism and role of hormones and “solvated electrons”
- Review Article
- 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
- Original Articles
- The potent inhibition of human cytosolic sulfotransferase 1A1 by 17α-ethinylestradiol is due to interactions with isoleucine 89 on loop 1
- In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values
- Regulation of flavin-containing mono-oxygenase (Fmo3) gene expression by steroids in mice and humans
Artikel in diesem Heft
- Frontmatter
- Letter to the Editor
-
Acute mental feelings and professional stress are controlling health. Mechanism and role of hormones and “solvated electrons”
- Review Article
- 5α-Reductase inhibitors alter steroid metabolism and may contribute to insulin resistance, diabetes, metabolic syndrome and vascular disease: a medical hypothesis
- Original Articles
- The potent inhibition of human cytosolic sulfotransferase 1A1 by 17α-ethinylestradiol is due to interactions with isoleucine 89 on loop 1
- In women, no significant variances of calculated free testosterone (cFT) are observed when a fixed value of albumin (Alb: 4.3 g/dL) is used instead of measured albumin values
- Regulation of flavin-containing mono-oxygenase (Fmo3) gene expression by steroids in mice and humans
