高胰岛素血症对多囊卵巢综合征肥胖女性血清性激素结合球蛋白水平的直接影响。

A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome.

作者信息

Nestler J E, Powers L P, Matt D W, Steingold K A, Plymate S R, Rittmaster R S, Clore J N, Blackard W G

机构信息

Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.

出版信息

J Clin Endocrinol Metab. 1991 Jan;72(1):83-9. doi: 10.1210/jcem-72-1-83.

DOI:10.1210/jcem-72-1-83

PMID:1898744

Abstract

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 less than 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 less than 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.

摘要

为了确定高胰岛素血症是否能直接降低患有多囊卵巢综合征的肥胖女性的血清性激素结合球蛋白（SHBG）水平，对6名患有该疾病的肥胖女性进行了研究。在研究前，于第-56、-28和0天，通过肌肉注射7.5mg长效GnRH激动剂亮丙瑞林缓释剂，抑制每位女性的卵巢类固醇生成。这导致血清睾酮浓度大幅降低（从第-56天的1.72±0.29nmol/L降至第0天的0.32±0.09nmol/L）、非SHBG结合睾酮（从第-56天的104±16pmol/L降至第0天的19±5pmol/L）、雄烯二酮（从第-56天的7.25±1.65nmol/L降至第0天的2.78±0.94nmol/L）、雌酮（从第-56天的371±71pmol/L降至第0天的156±29pmol/L）、雌二醇（从第-56天的235±26pmol/L降至第0天的90±24pmol/L）以及孕酮（从第-56天的0.28±0.12nmol/L降至第0天的0.08±0.02nmol/L）。然而，血清SHBG水平未发生变化（第-56天为18.8±（此处原文似乎有误，推测应为“±”）2.8nmol/L，第0天为17.8±2.6nmol/L）。在持续亮丙瑞林治疗的同时，给予这些女性口服二氮嗪（300mg/天），持续10天以抑制血清胰岛素水平。二氮嗪治疗导致100g口服葡萄糖耐量试验期间胰岛素释放受到抑制（曲线下胰岛素面积，第0天为262±55nmol/min·L，第10天为102±33nmol/min·L；P<0.05）以及葡萄糖耐量恶化。在二氮嗪和亮丙瑞林联合治疗期间，血清睾酮、雄烯二酮、雌酮、雌二醇和孕酮水平未发生变化。相比之下，血清SHBG水平从第0天的17.8±2.6nmol/L上升了32%，至第10天达到23.5±2.0nmol/L（P<0.003）。主要由于血清SHBG水平的升高，血清非SHBG结合睾酮水平从第0天的19±5pmol/L下降了43%，至第10天降至11±4pmol/L（P=0.05）。这些观察结果表明，高胰岛素血症可直接降低患有多囊卵巢综合征的肥胖女性血清SHBG水平，且与对血清性类固醇的任何影响无关。