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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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E. Diamanti-Kandarakis, A. Mitrakou, S. Raptis, G. Tolis, and A. J. Duleba The Effect of a Pure Antiandrogen Receptor Blocker, Flutamide, on the Lipid Profile in the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2699 - 2705. [Abstract] [Full Text]
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J. E. Nestler, D. J. Jakubowicz, W. S. Evans, and R. Pasquali Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome N. Engl. J. Med., June 25, 1998; 338(26): 1876 - 1880. [Abstract] [Full Text] [PDF]
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J. E. Nestler and D. J. Jakubowicz Lean Women with Polycystic Ovary Syndrome Respond to Insulin Reduction with Decreases in Ovarian P450c17{alpha} Activity and Serum Androgens J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 4075 - 4079. [Abstract] [Full Text] [PDF]
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D. J. Jakubowicz and J. E. Nestler 17{alpha}-Hydroxyprogesterone Responses to Leuprolide and Serum Androgens in Obese Women with and without Polycystic Ovary Syndrome after Dietary Weight Loss J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 556 - 560. [Abstract] [Full Text] [PDF]
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B. Andersson, L.-A. Mattsson, L. Hahn, L. Lapidus, G. Holm, B.-A. Bengtsson, and P. Bjorntorp Estrogen Replacement Therapy Decreases Hyperandrogenicity and Improves Glucose Homeostasis and Plasma Lipids in Postmenopausal Women With Noninsulin-Dependent Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 638 - 643. [Abstract] [Full Text] [PDF]
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J. E. Nestler and D. J. Jakubowicz Decreases in Ovarian Cytochrome P450c17{alpha} Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome N. Engl. J. Med., August 29, 1996; 335(9): 617 - 623. [Abstract] [Full Text] [PDF]
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R. D. Utiger Insulin and the Polycystic Ovary Syndrome N. Engl. J. Med., August 29, 1996; 335(9): 657 - 658. [Full Text]
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E. Diamanti-Kandarakis, G. Tolis, and A. J. Duleba Androgens and Therapeutic Aspects of Antiandrogens in Women Reproductive Sciences, July 1, 1995; 2(4): 577 - 592. [Abstract] [PDF]
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