Vrbíková J, Hill M, Stárka L, Cibula D, Bendlová B, Vondra K, Sulcová J, Snajderová M
Institute of Endocrinology, Prague, Czech Republic.
Eur J Endocrinol. 2001 Jun;144(6):619-28. doi: 10.1530/eje.0.1440619.
To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS).
Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used.
In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01).
Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.
评估多囊卵巢综合征（PCOS）女性长期服用二甲双胍治疗前后肾上腺和卵巢的类固醇生成情况。
对24名PCOS女性在使用二甲双胍（1000毫克/天）治疗前及治疗后（27±4周）进行评估，采用促肾上腺皮质激素（ACTH）、促性腺激素释放激素（GnRH）类似物及口服葡萄糖耐量（oGTT）试验。统计学评估采用方差分析和威尔科克森检验。
58%的女性月经周期有显著改善。基础类固醇水平无显著变化。ACTH刺激后，观察到C21类固醇中3β-羟类固醇脱氢酶活性显著降低（P<0.05），17β-羟类固醇脱氢酶活性显著降低（P<0.01），同时△4途径中C17,20-裂解酶活性增加（P<0.01）。检测到脱氢表雄酮（DHEA）/硫酸脱氢表雄酮比值显著升高（P<0.05）。关于卵巢类固醇生成，检测到刺激后的睾酮水平显著降低（P<0.05）、游离睾酮指数显著降低（P<0.01）、促黄体生成素（LH）显著降低（P<0.05）及雌二醇显著降低（P<0.01），同时17-羟孕烯醇酮水平升高（P<0.05）。在卵巢酶活性指标方面，观察到C21类固醇中3β-羟类固醇脱氢酶显著降低（P<0.01）、△5途径中C17,20-裂解酶显著降低（P<0.01）、17β-羟类固醇脱氢酶显著降低（P<0.05）及芳香化酶显著降低。在糖代谢方面，检测到稳态模型评估（HOMA）-R（胰岛素抵抗）和HOMA-F（β细胞功能）有降低趋势。此外，oGTT期间C肽水平升高（P<0.01）。
长期二甲双胍治疗可降低卵巢和肾上腺中多种类固醇酶活性，基础类固醇水平和胰岛素敏感性无明显变化。
