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The Biological Variation of Testosterone and Sex Hormone-Binding Globulin (SHBG) in Polycystic Ovarian Syndrome: Implications for SHBG as a Surrogate Marker of Insulin Resistance

Department of Medicine, University of Hull (V.J., P.E.J., D.A.H., S.L.A.), Department of Clinical Biochemistry and Immunology, Hull Royal Infirmary (E.S.K.), and York District General Hospital (P.E.J.), Hull, United Kingdom HU3 2RW

Address all correspondence and requests for reprints to: Dr. V. Jayagopal, University of Hull, Michael White Centre for Diabetes and Endocrinology, Hull Royal Infirmary, Anlaby Road, Hull, United Kingdom HU3 2RW. E-mail: v.jayagopal{at}hull.ac.uk.

This study was designed to assess the biological variability of total testosterone and SHBG in polycystic ovarian syndrome (PCOS) and to determine the use of SHBG as a surrogate marker of insulin resistance in PCOS. Fasting blood samples were collected at 4-d intervals on 10 consecutive occasions from 12 PCOS patients and 11 age- and weight-matched controls. Duplicate samples were analyzed for SHBG, testosterone, and insulin in a single batch, and insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR).

The PCOS group had higher testosterone (mean ± SD, 3.9 ± 0.8 vs. 3.2 ± 1.3 nmol/liter; P = 0.001), lower SHBG (28.6 ± 17.1 vs. 57.6 ± 30.2 nmol/liter; P = 0.001), and greater HOMA-IR (5.85 ± 5.3 vs. 1.67 ± 0.63 U; P = 0.001) than the controls. In contrast to HOMA-IR (1.09 vs. 0.48 U; P = 0.001), the intraindividual variation in SHBG was lower in the PCOS group (mean, 3.4 vs. 6.3 nmol/liter; P = 0.041). The index of individuality for SHBG and testosterone in PCOS was 0.49 and 0.69, respectively.

This study shows that for patients with PCOS, SHBG is an integrated marker of insulin resistance that may be of use to identify insulin-resistant individuals for targeted treatment with insulin-sensitizing agents. However, SHBG and testosterone concentrations measured in isolation are inherently unsuitable for use as tests to detect hyperandrogenemia.

Abbreviations: FAI, Free androgen index; HOMA, homeostasis model assessment method; HOMA-IR, insulin resistance calculated by the homeostasis model assessment method; IoI, index of individuality; PCOS, polycystic ovarian syndrome.

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