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A Direct Effect of Hyperinsulinemia on Serum Sex Hormone-Binding Globulin Levels in Obese Women with the Polycystic Ovary Syndrome^*

Departments of Medicine (J.E.N., L.P.P., J.N.C., W.G.B.) and Obstetrics and Gynecology (D.W.M., K.A.S.), Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298
the Department of Clinical Investigation (S.R.P.), Madigan Army Medical Center Tacoma, Washington 98431
the Division of Endocrinology, Halifax Infirmary (R.S.R.) Halifax, Nova Scotia, Canada

Address all correspondence and requests for reprints to: John E. Nestler, M.D., Division of Endocrinology and Metabolism, Medical College of Virginia, MCV Station, Box 111, Richmond, Virginia 23298–0111.

To determine whether hyperinsulinemia can directly reduce serum sex hormone-binding globulin (SHBG) levels in obese women with the polycystic ovary syndrome, six obese women with this disorder were studied. Before study, ovarian steroid production was suppressed in each woman by the administration of 7.5 mg of a long-acting GnRH agonist, leuprolide depot, im, on days –56, –28, and 0. This resulted in substantial reductions in serum concentrations of testosterone (from 1.72 ± 0.29 nmol/L on day –56 to 0.32 ± 0.09 nmol/L on day 0), non-SHBG-bound testosterone (from 104 ± 16 pmol/L on day –56 to 19 ± 5 pmol/L on day 0), androstenedione (from 7.25 ± 1.65 nmol/L on day –56 to 2.78 ± 0.94 nmol/L on day 0), estrone (from 371 ± 71 pmol/L on day –56 to 156 ± 29 pmol/L on day 0), estradiol (from 235 ± 26 pmol/L on day –56 to 90 ± 24 pmol/L on day 0), and progesterone (from 0.28 ± 0.12 nmol/L on day –56 to 0.08 ± 0.02 nmol/L on day 0). Serum SHBG levels, however, did not change (18.8 ± 2.8 nmol/L on day –56 vs. 17.8 ± 2.6 nmol/L on day 0).

While continuing leuprolide treatment, the women were administered oral diazoxide (300 mg/day) for 10 days to suppress serum insulin levels. Diazoxide treatment resulted in suppressed insulin release during a 100-g oral glucose tolerance test (insulin area under the curve, 262 ± 55 nmol/min·L on day 0 vs. 102 ± 33 nmol/min·L on day 10; P < 0.05) and deterioration of glucose tolerance. Serum testosterone, androstenedione, estrone, estradiol, and progesterone levels did not change during combined diazoxide and leuprolide treatment. In contrast, serum SHBG levels rose by 32% from 17.8 ± 2.6 nmol/L on day 0 to 23.5 ± 2.0 nmol/L on day 10 (P < 0.003). Due primarily to the rise in serum SHBG levels, serum non-SHBG-bound testosterone levels fell by 43% from 19 ± 5 pmol/L on day 0 to 11 ± 4 pmol/L on day 10 (P = 0.05). These observations suggest that hyperinsulinemia directly reduces serum SHBG levels in obese women with the polycystic ovary syndrome independently of any effect on serum sex steroids.

^* This work was supported in part by NIH Grants RR-00065 and DK-18904, a Research Award from the Virginia Affiliate of the American Diabetes Association, and the Thomas F. and Kate Miller Jeffress Memorial Trust.

Received June 13, 1990.

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