Diagnostic value of calculated testosterone indices in the assessment of polycystic ovary syndrome
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Susanne Hahn
Abstract
Background: One of the main criteria to establish a diagnosis of polycystic ovary syndrome (PCOS) is hyperandrogenemia. Recent observations suggest that total testosterone may not be a sensitive marker for the detection of androgen excess. The aim of the present study was to compare the value of different androgen determinations for diagnosis of PCOS.
Methods: Untreated PCOS patients (n=133; mean age 28 years) and healthy control women (n=54; mean age 28 years) were included in the study. Measurements of total testosterone and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstendione, dehydroepiandrosterone sulfate (DHEAS) and albumin were performed. In addition, the free androgen index (FAI), free and bioavailable testosterone were calculated. Clinical signs of hyperandrogenism were evaluated by physical examination. The area under the receiver operating characteristic curve (AUC-ROC) was used to compare the sensitivity and specificity of different androgen determinations to detect PCOS, defined as clinical hyperandrogenism and irregular cycles compatible with the National Institutes of Health criteria of chronic anovulation and clinical or biochemical hyperandrogenism.
Results: All biochemical parameters of hyperandrogenism were significantly higher in PCOS patients than in controls (all p<0.0001). The highest AUC-ROC was found for bioavailable testosterone (0.852) followed by FAI (0.847) and free testosterone (0.837). Lower AUC-ROC was found for SHBG, total testosterone and androstendione (0.765, 0.799 and 0.706, respectively). When FAI=4.97 was taken as a cutoff value, sensitivity was 71.4% and specificity was 85.2%. A cutoff of 0.78 nmol/L for bioavailable testosterone had even higher sensitivity of 75.9%, but slightly lower specificity of 83.3%. FAI and bioavailable testosterone correlated significantly (all p<0.05) with total testosterone, androstendione, LH/FSH ratio and DHEAS. In addition, free testosterone, bioavailable testosterone and FAI correlated significantly with hirsutism scores, and ovarian volume and follicle count.
Conclusions: ROC analysis provided evidence that calculated testosterone indices (bioavailable testosterone, FAI, free testosterone) are useful parameters for the discrimination of PCOS patients and healthy controls.
Clin Chem Lab Med 2007;45:202–7.
References
1. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab2000;85:2434–8.10.1210/jc.85.7.2434Suche in Google Scholar
2. Carmina E. Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM guidelines. Minerva Ginecol2004;56:1–6.Suche in Google Scholar
3. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev1997;18:774–800.10.1210/edrv.18.6.0318Suche in Google Scholar
4. ESHRE/ASRM. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19–25.10.1016/j.fertnstert.2003.10.004Suche in Google Scholar
5. Goodenough DJ, Rossmann K, Lusted LB. Radiographic applications of receiver operating characteristic (ROC) curves. Radiology1974;110:89–95.10.1148/110.1.89Suche in Google Scholar
6. Lusted LB. Signal detectability and medical decision-making. Science1971;171:1217–9.10.1126/science.171.3977.1217Suche in Google Scholar
7. Lusted LB. General problems in medical decision making with comments on ROC analysis. Semin Nucl Med1978;8:299–306.10.1016/S0001-2998(78)80015-4Suche in Google Scholar
8. Turhan NO, Toppare MF, Seckin NC, Dilmen G. The predictive power of endocrine tests for the diagnosis of polycystic ovaries in women with oligoamenorrhea. Gynecol Obstet Invest1999;48:183–6.10.1159/000010170Suche in Google Scholar
9. Koskinen P, Penttila TA, Anttila L, Erkkola R, Irjala K. Optimal use of hormone determinations in the biochemical diagnosis of the polycystic ovary syndrome. Fertil Steril1996;65:517–22.10.1016/S0015-0282(16)58146-1Suche in Google Scholar
10. Escobar-Morreale HF, Asuncion M, Calvo RM, Sancho J, San Millan JL. Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies. Eur J Endocrinol2001;145:619–24.10.1530/eje.0.1450619Suche in Google Scholar PubMed
11. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab2004;89:2745–9.10.1210/jc.2003-032046Suche in Google Scholar PubMed
12. Cumming DC, Wall SR. Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism. J Clin Endocrinol Metab1985;61:873–6.10.1210/jcem-61-5-873Suche in Google Scholar
13. Mueller A, Dittrich R, Cupisti S, Beckmann MW, Binder H. Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone. Exp Clin Endocrinol Diabetes2006;114:182–7.10.1055/s-2006-924062Suche in Google Scholar
14. Ludwig E. Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex. Br J Dermatol1977;97:247–54.10.1111/j.1365-2133.1977.tb15179.xSuche in Google Scholar
15. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia1985;28:412–9.10.1007/BF00280883Suche in Google Scholar
16. Babson AL, Olson DR, Palmieri T, Ross AF, Becker DM, Mulqueen PJ. The IMMULITE assay tube: a new approach to heterogeneous ligand assay. Clin Chem1991;37:1521–2.10.1093/clinchem/37.9.1521Suche in Google Scholar
17. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab1999;84:3666–72.10.1210/jcem.84.10.6079Suche in Google Scholar
18. Bender R, Lange S, Ziegler A. Wichtige Signifikanztests. Dtsch Med Wochenschr2002;127:T1–3.10.1055/s-2002-32820Suche in Google Scholar
19. Hahn S, Tan S, Elsenbruch S, Quadbeck B, Herrmann BL, Mann K, et al. Clinical and biochemical characterization of women with polycystic ovary syndrome in North Rhine-Westphalia. Horm Metab Res2005;37:438–44.10.1055/s-2005-870236Suche in Google Scholar
20. Vermeulen A, Stoica T, Verdonck L. The apparent free testosterone concentration, an index of androgenicity. J Clin Endocrinol Metab1971;33:759–67.10.1210/jcem-33-5-759Suche in Google Scholar
21. O'Connor S, Baker HW, Dulmanis A, Hudson B. The measurement of sex steroid binding globulin by differential ammonium sulphate precipitation. J Steroid Biochem1973;4:331–9.10.1016/0022-4731(73)90002-2Suche in Google Scholar
22. Herold DA, Fitzgerald RL. Immunoassays for testosterone in women: better than a guess? Clin Chem2003;49:1250–1.10.1373/49.8.1250Suche in Google Scholar
23. Rosner W. An extraordinary inaccurate assay for free testosterone is still with us. J Clin Endocrinol Metab2001;86:2903.10.1210/jcem.86.6.7643Suche in Google Scholar
24. Ross HA, Meuleman EJ, Sweep FC. A simple method for estimating equilibrium constants for serum testosterone binding resulting in an optimal free testosterone index for use in elderly men. Clin Chem Lab Med2005;43:613–6.10.1515/CCLM.2005.106Suche in Google Scholar
25. Hahn S, Haselhorst U, Quadbeck B, Tan S, Kimmig R, Mann K, et al. Decreased soluble leptin receptor levels in women with polycystic ovary syndrome. Eur J Endocrinol2006;154:287–94.10.1530/eje.1.02078Suche in Google Scholar
26. Bernasconi D, Del Monte P, Meozzi M, Randazzo M, Marugo A, Badaracco B, et al. The impact of obesity on hormonal parameters in hirsute and nonhirsute women. Metabolism1996;45:72–5.10.1016/S0026-0495(96)90202-4Suche in Google Scholar
27. Peiris AN, Sothmann MS, Aiman EJ, Kissebah AH. The relationship of insulin to sex hormone-binding globulin: role of adiposity. Fertil Steril1989;52:69–72.10.1016/S0015-0282(16)60791-4Suche in Google Scholar
28. Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab1991;72:83–9.10.1210/jcem-72-1-83Suche in Google Scholar PubMed
29. Hahn S, Tan S, Sack S, Kimmig R, Quadbeck B, Mann K, et al. Prevalence of the metabolic syndrome in German women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes2006;114:1–7.10.1055/s-2006-932980Suche in Google Scholar
30. 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 Metab2004;89:534–43.10.1210/jc.2003-031287Suche in Google Scholar PubMed
31. Miller KK, Rosner W, Lee H, Hier J, Sesmilo G, Schoenfeld D, et al. Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. J Clin Endocrinol Metab2004;89:525–33.10.1210/jc.2003-030680Suche in Google Scholar PubMed
©2007 by Walter de Gruyter Berlin New York
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