Leeds Teaching Hospitals, NHS Trust, Leeds, United Kingdom.
Eur J Obstet Gynecol Reprod Biol. 2011 May;156(1):67-71. doi: 10.1016/j.ejogrb.2010.12.041. Epub 2011 Feb 1.
The benefit of metformin on polycystic ovary syndrome (PCOS) has been debated. Varying results have been observed in different studies which could be due to differences in the study cohorts and the heterogeneity of the syndrome. We hypothesized that the dose of metformin generally used may not be adequate for women with higher BMI and observed the effect of dose escalation on PCOS in women with differing BMI and baseline insulin resistance.
Forty women were recruited to the study. Patients were started on 1g/day and increased every 8 weeks by 1-3g at the end of 16 weeks. The study was carried out for 24 weeks. Analysis was carried out based on BMI and baseline insulin sensitivity. There were four groups based on BMI with 10 patients in each group (groups A: 18-24.9 kg/m(2), B: 25-29.9 kg/m(2), C: 30-34.9 kg/m(2) and D: 35-40 kg/m(2)). There were three tertiles based on insulin sensitivity. In order of insulin resistance, tertile 1 (n=13) - high insulin resistance (IR), tertile 2 (n=13) - mid IR, tertile 3 (n=14) - low IR. The outcome measures were clinical features, insulin sensitivity and androgens.
A trend towards reduction of fasting insulin concentration was observed which reached statistical significance (p<0.05) in group D. At the highest dose of 3g, groups B and C also showed a decrease in insulin concentrations but statistical significance was not achieved. On examination of changes in insulin resistance over time, groups B, C and D showed a trend towards improvement in sensitivity but QUICKI remained below 0.333. No definite benefit from higher doses was seen. When analyzed based on the three tertiles, there was significant drop in fasting insulin concentration in the first tertile (-16.73 ± 9.8 nmol/L). Measurement of QUICKI also revealed a significant improvement in the first tertile (p=0.001).
There is no benefit from increased doses of metformin in PCOS but reduction of insulin resistance is more significant in those patients with a lower insulin sensitivity at baseline.
二甲双胍对多囊卵巢综合征（PCOS）的益处一直存在争议。不同的研究结果有所不同，这可能是由于研究队列的差异和综合征的异质性所致。我们假设，一般使用的二甲双胍剂量可能对 BMI 较高的女性不够，因此观察了不同 BMI 和基线胰岛素抵抗的女性中剂量递增对 PCOS 的影响。
招募了 40 名女性参加研究。患者每天服用 1g，16 周结束时每 8 周增加 1-3g。该研究进行了 24 周。根据 BMI 和基线胰岛素敏感性进行分析。根据 BMI 有 4 组，每组 10 名患者（A 组：18-24.9kg/m2；B 组：25-29.9kg/m2；C 组：30-34.9kg/m2；D 组：35-40kg/m2）。根据胰岛素敏感性分为 3 个三分位数。按胰岛素抵抗程度，第 1 三分位数（n=13）为高胰岛素抵抗（IR），第 2 三分位数（n=13）为中 IR，第 3 三分位数（n=14）为低 IR。观察指标为临床特征、胰岛素敏感性和雄激素。
观察到空腹胰岛素浓度呈下降趋势，D 组达到统计学意义（p<0.05）。在最高剂量 3g 时，B 组和 C 组的胰岛素浓度也有所下降，但未达到统计学意义。检查随时间推移胰岛素抵抗的变化，B、C 和 D 组的敏感性呈改善趋势，但 QUICKI 仍低于 0.333。没有看到更高剂量的明确益处。根据三个三分位数进行分析时，第一三分位数的空腹胰岛素浓度显著下降（-16.73±9.8nmol/L）。QUICKI 的测量也显示第一三分位数有显著改善（p=0.001）。
PCOS 中增加二甲双胍剂量没有益处，但在基线胰岛素敏感性较低的患者中，胰岛素抵抗的降低更为明显。
