A DIRECT EFFECT OF HYPERINSULINEMIA ON SERUM SEX HORMONE-BINDING GLOBULIN LEVELS IN OBESE WOMEN WITH THE POLYCYSTIC-OVARY-SYNDROME

A DIRECT EFFECT OF HYPERINSULINEMIA ON SERUM SEX HORMONE-BINDING GLOBULIN LEVELS IN OBESE WOMEN WITH THE POLYCYSTIC-OVARY-SYNDROME
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DOI:
10.1210/jcem-72-1-83
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发表时间:
1991-01-01
影响因子:
5.8
通讯作者:
BLACKARD, WG
BLACKARD, WG
中科院分区:
医学2区
文献类型:
--
作者:
NESTLER, JE;POWERS, LP;BLACKARD, WG

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为了确定高胰岛素血症是否能直接降低肥胖多囊卵巢综合征妇女的血清性激素结合球蛋白(SHBG)水平,我们对6名肥胖多囊卵巢综合征妇女进行了研究。在研究之前,每位女性在第56天、第28天和第0天服用长效GnRH激动剂leuprolide depot 7.5 mg,可抑制卵巢类固醇的产生。这导致大幅降低血清睾酮浓度(从1.72 + / - 0.29 nmol / L天-56 - 0.32 + / - 0.09 nmol / L 0)天,non-SHBG-bound睾酮(104 + / - 16 pmol / L -56 - 19天+ / - 5 0天pmol / L),雄烯二酮(从7.25 + / - 1.65 nmol / L天-56 - 2.78 + / - 0.94 nmol / L天0),雌激素酮(371 + / - 71 pmol / L -56到156天+ / - 29天pmol / L 0),雌二醇(235 + / - 26 pmol / L -56到90天+ / - 24天pmol / L 0),黄体酮(从-56天的0.28 +/- 0.12 nmol/L到第0天的0.08 +/- 0.02 nmol/L)。然而,血清SHBG水平没有变化(第56天为18.8 +/- 2.8 nmol/L,第0天为17.8 +/- 2.6 nmol/L)。在继续使用leuprolide治疗的同时,妇女服用口服二氮氧化物(300毫克/天)10天以抑制血清胰岛素水平。在100 g口服葡萄糖耐量试验中,二氮氧化合物抑制胰岛素释放(胰岛素曲线下面积,262 +/- 55 nmol/min)。L在第0天vs. 102 +/- 33 nmol/min。L第10天;P < 0.05)和糖耐量下降。血清睾酮、雄烯二酮、雌酮、雌二醇和黄体酮水平在二氮氧化合物和leuprolide联合治疗期间没有变化。相比之下,血清SHBG水平从第0天的17.8 +/- 2.6 nmol/L上升到第10天的23.5 +/- 2.0 nmol/L,上升了32% (P < 0.003)。主要由于血清SHBG水平升高,血清非SHBG结合睾酮水平从第0天的19 +/- 5 pmol/L下降到第10天的11 +/- 4 pmol/L,下降了43% (P = 0.05)。这些观察结果表明,高胰岛素血症可以直接降低多囊卵巢综合征肥胖妇女的血清SHBG水平,而不依赖于对血清性类固醇的任何影响。
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.