Unlühizarci K, Keleştimur F, Sahin Y, Bayram F
Department of Endocrinology, Erciyes University School of Medicine, Kayseri, Turkey.
Eur J Endocrinol. 1999 Jan;140(1):56-61. doi: 10.1530/eje.0.1400056.
To determine whether metformin. when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17alpha enzyme in patients with PCOS.
We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily, for 12 weeks).
The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women.
Women with PCOS were hyperinsulinemic (102.0+/-13.0 (S.E.M.) VS 46.2+/-4.4 pmol/l) and hyperandrogenemic (free testosterone 15.3+/-1.7 vs 7.9+/-0.6 nmol/l; androstenedione 11.8+/-0.8 vs 8.2+/-0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7+/-1.6 vs 3.0+/-0.3) than healthy women. In addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin.
PCOS is characterized by hyperactivity of the adrenal P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.
确定二甲双胍用于患有多囊卵巢综合征（PCOS）的非糖尿病女性时，在维持体重的同时是否能降低胰岛素抵抗和高胰岛素血症。我们还旨在观察胰岛素水平的降低是否会减弱PCOS患者肾上腺P450c17α酶的活性。
我们在二甲双胍治疗前后（500毫克，口服，每日两次，共12周），研究了促肾上腺皮质激素（ACTH）刺激后的17-羟孕酮（17-OHP）和雄烯二酮反应、口服葡萄糖耐量试验（OGTT）中的胰岛素反应以及胰岛素耐量试验中的葡萄糖处置率。
通过OGTT证实15名PCOS女性存在高胰岛素血症，并将结果与10名健康女性的结果进行比较。胰岛素敏感性通过静脉推注胰岛素后内源性葡萄糖处置率来测量。在所有PCOS女性和正常女性中测量ACTH刺激后的17-OHP和雄烯二酮反应。
PCOS女性存在高胰岛素血症（102.0±13.0（标准误）对46.2±4.4皮摩尔/升）和高雄激素血症（游离睾酮15.3±1.7对7.9±0.6纳摩尔/升；雄烯二酮11.8±0.8对8.2±0.6纳摩尔/升），且比健康女性多毛（改良的费里曼-盖尔韦评分，17.7±1.6对3.0±0.3）。此外，与健康女性相比，PCOS女性对ACTH的17-OHP和雄烯二酮反应更高。二甲双胍治疗使胰岛素敏感性有所改善，并降低了基础和葡萄糖负荷后胰岛素水平。但二甲双胍治疗后，ACTH刺激后的17-OHP和雄烯二酮反应未改变。
PCOS的特征是肾上腺P450c17α酶活性过高和胰岛素抵抗。胰岛素抵抗与肾上腺P450c17α酶失调之间似乎没有直接关系。
