Silfen Miriam E, Denburg Michelle R, Manibo Alexandra M, Lobo Rogerio A, Jaffe Richard, Ferin Michel, Levine Lenore S, Oberfield Sharon E
Department of Pediatrics, Division of Pediatric Endocrinology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
J Clin Endocrinol Metab. 2003 Oct;88(10):4682-8. doi: 10.1210/jc.2003-030617.
Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.
大约一半的多囊卵巢综合征（PCOS）女性超重或肥胖，并且研究报告了PCOS的瘦型和肥胖型女性之间存在内分泌和代谢差异。PCOS在青少年人群中尚未得到广泛研究。我们研究的目的是进一步描述PCOS青少年早期的内分泌和代谢改变，并确定PCOS的非肥胖和肥胖女性之间的差异在病程早期是否存在。我们研究了48名青少年组成的种族异质群体：11名非肥胖PCOS患者[年龄，16.1±1.9岁；体重指数（BMI），22.5±1.5kg/m²]，22名肥胖PCOS患者（年龄，15.5±1.4岁；BMI，35.9±6.2kg/m²），以及15名肥胖对照者（年龄，14.4±1.5岁；BMI，35.8±7.1kg/m²）。测量了空腹血糖、胰岛素、胰岛素原、糖化血红蛋白A1c、睾酮、性激素结合球蛋白（SHBG）、δ4-雄烯二酮（δ4-A）、硫酸脱氢表雄酮（DHEAS）、促黄体生成素（LH）、促卵泡生成素（FSH）、胰岛素样生长因子-I（IGF-I）、IGF结合蛋白-1、游离IGF-I和血脂水平。11名非肥胖PCOS受试者中的6名、22名肥胖PCOS受试者中的11名以及15名对照者中的6名接受了标准口服葡萄糖耐量试验。通过曲线下胰岛素面积（I(AUC120)）测量口服葡萄糖耐量试验的胰岛素反应。胰岛素敏感性指标计算为空腹血糖与胰岛素比值、定量胰岛素敏感性检查指数和综合胰岛素敏感性指数。与肥胖PCOS组相比，非肥胖PCOS青少年的LH、SHBG、δ4-A、DHEAS、双氢睾酮、游离IGF-I水平更高，低密度脂蛋白水平更低。与非肥胖PCOS受试者相比，肥胖者的空腹胰岛素和胰岛素原水平、I(AUC120)以及log I(AUC120)更高，空腹血糖与胰岛素比值、定量胰岛素敏感性检查指数和综合胰岛素敏感性指数更低。与肥胖对照组相比，肥胖PCOS组的LH和雄激素水平更高，包括总睾酮和游离睾酮、δ4-A和DHEAS，而SHBG水平更低。PCOS青少年表现出与成年女性相似的临床、代谢和内分泌特征，并且PCOS的非肥胖和肥胖女性之间的差异在青春期即可检测到。我们的研究结果表明，非肥胖PCOS青少年的下丘脑-垂体-肾上腺轴改变更为明显，而肥胖的PCOS青少年胰岛素水平调节更为显著且胰岛素敏感性受损。我们的数据还提示非肥胖和肥胖PCOS青少年在IGF系统方面存在差异。
