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中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (06) : 739 -746. doi: 10.3877/cma.j.issn.1673-5250.2015.06.013

所属专题： 文献；

论著

不同胰岛素增敏剂对多囊卵巢综合征的临床疗效研究
丛新茹1, 郭雪桃1,*,*(), 成贇1, 杨嘉琦1, 周梦1   
  1. 1. 030001　太原，山西医科大学第一医院妇产科
  • 收稿日期:2015-10-08 修回日期:2015-11-15 出版日期:2015-12-01
  • 通信作者: 郭雪桃

Comparison of clinical effects of different insulin sensitizing agents treatment on polycystic ovary syndrome

Xinru Cong1, Xuetao Guo1(), Yun Cheng1, Jiaqi Yang1, Meng Zhou1   

  1. 1. Department of Gynaecology and Obstetrics, First Affiliated Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
  • Received:2015-10-08 Revised:2015-11-15 Published:2015-12-01
  • Corresponding author: Xuetao Guo
  • About author:
    Corresponding author: Guo Xuetao, Email :
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引用本文：

丛新茹, 郭雪桃, 成贇, 杨嘉琦, 周梦. 不同胰岛素增敏剂对多囊卵巢综合征的临床疗效研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2015, 11(06): 739-746.

Xinru Cong, Xuetao Guo, Yun Cheng, Jiaqi Yang, Meng Zhou. Comparison of clinical effects of different insulin sensitizing agents treatment on polycystic ovary syndrome[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(06): 739-746.

目的

探讨胰岛素增敏剂二甲双胍、吡格列酮及二者联合治疗多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)的临床疗效。

方法

选择2012年1月至2014年10月于山西医科大学第一医院妇产科内分泌门诊确诊为PCOS合并IR的90例患者为研究对象。采用随机数字表法将其分为二甲双胍组(n＝30)、吡格列酮组(n＝30)和联合组(n＝30)。本研究遵循的程序符合病例纳入医院人体试验委员会所制定的伦理学标准，得到该委员会批准，分组征得受试对象本人的知情同意，并与之签署临床研究知情同意书。3组PCOS合并IR患者在长期接受生活方式干预(饮食控制及有氧锻炼)基础上，分别进行药物治疗。观察3组患者治疗前、后一般临床资料，体格测量指标，内分泌激素指标，IR评价指标和生化指标变化。计算3组患者2个月经周期基础体温(BBT)双相率或妊娠率。

结果

3组PCOS合并IR患者治疗前一般临床资料、体格测量指标、内分泌激素指标和生化指标比较，差异均无均无统计学意义(P>0.05)。3组PCOS合并IR患者治疗后，胰岛素释放曲线下面积(AUCINS)、腰围、血清睾酮水平均显著低于治疗前，且差异均有统计学意义(P<0.05)。治疗后二甲双胍组和联合组患者的体质指数(BMI)，吡格列酮组和联合组患者的腰臀比(WHR)和高密度脂蛋白(HDL)，联合组患者的胰岛素抵抗指数稳态模型评估指数(HOMA-IR)，均较治疗前显著改善，各组治疗前、后上述指标分别比较，差异均有统计学意义(P<0.05)。治疗后，联合组患者BMI降低程度高于吡格列酮组[(－1.62±1.61) kg/m2 vs (0.08±1.97) kg/m2]，两组比较，差异有统计学意义(H＝0.730，P<0.05)；吡格列酮组和联合组患者WHR降低程度，均显著高于二甲双胍组[(－0.03±0.03)和(－0.04±0.06)分别与(－0.01±0.02)比较]，并且差异也均有统计学意义(H＝6.911，9.813；P<0.05)。3组PCOS合并IR患者治疗后2个月经周期的BBT双相率分别为53.3%，40.0%和33.3%，妊娠率分别为6.7%，20.0%和16.7%，3组比较，差异均无统计学意义(P>0.05)。

结论

胰岛素增敏剂治疗可有效改善PCOS患者的IR状态，同时可降低血清睾酮水平，降低患者BMI。二甲双胍和吡格列酮联合用药改善IR的疗效优于二者单独使用。二甲双胍对降低患者BMI更具优势，吡格列酮对升高HDL和降低WHR效果更明显。

关键词: 多囊卵巢综合征, 胰岛素抗药性, 二甲双胍, 吡格列酮, 女性
Objective

To study the clinical effects of treatment by metformin, pioglitazone, and combination of metformin and pioglitazone on polycystic ovary syndrome(PCOS) patients complicated with insulin resistance (IR).

Methods

From January 2012 to October 2014, a total of 90 women who were diagnosed as PCOS complicated with IR in the First affiliated Hospital of Shanxi Medical University were recruited in the study. They were randomly divided into metformin group(n=30), pioglitazone group (n=30) and combination group(n=30) by random digital table method.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of the First Affiliated Hospital of Shanxi Medical University.Informed consent was obtained from each participant. Lifestyle intervention and different drug treatment were given among three groups. General clinical data, physical measurement indexes, endocrine hormone indexes, IR evaluation indexes and biochemical indicators were observed among three groups. The duplex rates of basal body temperature(BBT) and pregnancy rates in three groups were statistical analysis.

Results

There were no significant differences among three groups in general clinical data physical measurement indexes, endocrine hormone indexes, IR evaluation indexes and biochemical indicators before treatment(P>0.05). Compared with before treatment, area under the curve of insulin release(AUCINS), waist circumference, levels of serum testosterone in three groups were remarkably lower than those in the same groups after treatment, and there were significant differences (P<0.05). Body mass index(BMI)in metformin group and combination group, waist to hip ratio(WHR), levels of high density lipoprotein(HDL) in pioglitazone group and combination group, homeostasis model of assessment for insulin resistence index(HOMA-IR) in combination group were much higher than those in the same groups after treatment, respectively(P<0.05). After treatment, the decrease of BMI in combination group were remarkably lower than those of metformin group [(-1.62±1.61) kg/m2 vs (0.08±1.97) kg/m2], meanwhile the decrease of WHR in pioglitazone group and combination group were remarkably lower than those of metformin group [(-0.03±0.03) and (-0.01±0.02) vs (-0.04±0.06)], all the differences above were significant (H=0.730, 6.911, 9.813; P<0.05). After treatment, the duplex rates of BBT in three groups were 53.3%, 40.0%, 33.3%, and the pregnancy rates were 6.7%, 20.0% and 16.7%, respectively.There were no significant differences among three groups in both rates above(P>0.05).

Conclusions

Most PCOS patients complication with IR. Insulin-sensiting agants can effectively improve their symptoms of IR, and can significantly improve hyperandrogenemia and reduce accumulation of abdominal visceral fat.Treatment by metformin combination of pioglitazone is more effective than single use of each of them for ameliorating IR.Metformin could have more advantages in losing weight of PCOS patients than that of pioglitazone , and pioglitazone can significantly raise HDL and reduce WHR of PCOS patients than that of metformin.

Key words: Polycystic ovary syndrome, Insulin resistance, Metformin, Pioglitazone, Female
表1 治疗前3组PCOS合并IR患者基线水平的比较[M(P25～P75)]
组别 例数 一般情况 体格测量指标 内分泌激素指标 IR评价指标 生化指标
年龄(±s，岁) 初潮年龄(±s，岁) 收缩压(±s，mmHg) 舒张压(±s，mmHg) BMI(kg/m2) 腰围(cm) WHR 睾酮(ng/mL) LH/FSH FINS(mIU/L) HOMA-IR AUCINS(mIU/L) TC(mmol/L) TG(mmol/L) HDL(mmol/L) LDL(mmol/L)
二甲双胍组 30 23.9±3.5 13.0±1.0 110.0±26.0 80.0± 8.5 26.37(23.12～30.88) 81.00(76.12～94.12) 0.85(0.79～0.89) 1.00(0.63～1.53) 2.34(1.72～3.07) 20.12(13.37～35.07) 4.50(1.52～7.52) 400.12(312.55～535.90) 4.43(4.11～5.15) 1.54(1.23～1.96) 1.16(1.06～1.29) 2.50(2.06～3.18)
吡格列酮组 30 26.5±3.7 13.0±1.0 110.0± 8.5 71.0±10.0 26.13(24.28～29.33) 85.00(80.10～93.40) 0.88(0.83～0.96) 0.99(0.72～1.50) 2.39(2.07～3.05) 19.67(11.37～31.19) 5.04(3.91～6.50) 358.17(273.55～496.63) 4.54(4.23～4.92) 1.02(0.60～1.70) 1.30(1.20～1.56) 2.64(2.31～3.35)
联合组 30 24.4±4.4 13.0±1.0 120.0±17.0 79.0± 8.5 30.13(29.20～36.90) 87.50(78.13～98.88) 0.88(0.86～1.03) 1.28(0.91～1.73) 2.58(2.13～3.30) 24.33(14.82～38.53) 6.081(1.83～9.85) 449.89(371.19～560.41) 4.87(4.49～5.39) 1.59(1.25～2.14) 1.44(1.32～2.09) 3.01(2.42～3.85)
F值/H值 ? 2.749 0.878 1.144 5.265 4.770 3.085 2.668 3.481 0.919 2.191 3.625 1.163 2.119 4.577 0.715 0.810
P值 ? 0.070 0.645 0.564 0.072 0.092 0.214 0.075 0.175 0.403 0.334 0.163 0.317 0.127 0.101 0.492 0.448
表2 二甲双胍组PCOS合并IR患者治疗前、后观察指标的比较[M(P25～P75)]
组别 例数 BMI(kg/m2) 腰围(cm) WHR 睾酮(ng/mL) LH/FSH FINS(mIU/L) HOMA-IR AUCINS(mIU/L) TC(mmol/L) TG(mmol/L) HDL(mmol/L) LDL(mmol/L)
治疗前 30 26.37(23.12～30.88) 87.00(76.12～94.12) 0.85(0.79～0.89) 1.05(0.71～1.22) 2.34(1.72～3.07) 20.12(13.37～35.07) 4.50(1.52～7.52) 400.12(312.55～535.90) 4.43(4.11～5.15) 1.54(1.23～1.96) 1.16(1.06～1.29) 2.50(2.06～3.18)
治疗后 30 24.88(22.53～25.11) 83.56(79.86～86.85) 0.84(0.82～0.86) 0.73(0.54～1.14) 2.06(1.55～2.81) 17.28(13.79～25.61) 4.09(3.27～5.62) 237.88(112.34～349.96) 4.22(4.02～4.79) 1.17(0.82～1.66) 1.17(1.04～1.34) 2.29(2.03～2.83)
Z值 ? －3.820 －4.024 －1.206 －2.745 －2.068 －0.813 －0.902 －2.632 1.495 －1.587 －0.065 －0.081
P值 ? <0.001 <0.001 0.228 0.006 0.039 0.416 0.368 0.009 0.135 0.113 0.948 0.936
表3 吡格列酮组PCOS合并IR患者治疗前、后观察指标比较[M(P25～P75)]
组别 例数 BMI(kg/m2) 腰围(cm) WHR 睾酮(ng/mL) LH/FSH FINS(mIU/L) HOMA-IR AUCINS(mIU/L) TC(mmol/L) TG(mmol/L) HDL(mmol/L) LDL(mmol/L)
治疗前 30 26.13(24.28～29.33) 85.72(80.10～93.40) 0.88(0.83～0.96) 1.29(1.08～1.68) 2.39(2.07～3.05) 19.67(11.37～31.19) 5.04(3.91～6.50) 358.17(273.55～496.63) 4.54(4.23～4.92) 1.02(0.60～1.70) 1.30(1.20～1.56) 2.64(2.31～3.35)
治疗后 30 25.24(23.16～28.19) 79.50(77.05～84.87) 0.83(0.81～0.86) 0.82(0.66～1.06) 2.79(1.42～4.40) 17.76(16.15～22.43) 3.58(2.98～4.74) 252.81(161.14～311.08) 4.46(4.11～5.01) 1.01(0.51～1.81) 1.43(1.21～1.71) 2.44(2.22～3.03)
Z值 ? －1.935 －4.070 －4.156 －2.316 －0.051 －1.093 －1.298 －2.459 －1.125 －0.043 －2.441 －1.369
P值 ? 0.053 <0.001 <0.001 0.021 0.959 0.274 0.194 0.014 0.260 0.966 0.021 0.171
表4 联合组PCOS合并IR患者观察指标比较[M(P25～P75)]
组别 例数 BMI(kg/m2) 腰围(cm) WHR 睾酮(ng/mL) LH/FSH FINS(mIU/L) HOMA-IR AUCINS(mIU/L) TC(mmol/L) TG(mmol/L) HDL(mmol/L) LDL(mmol/L)
治疗前 30 30.13(29.20～36.90) 90.00(85.71～102.03) 0.91(0.86～1.03) 1.28(0.98～1.68) 2.58(2.13～3.30) 24.33(14.82～38.53) 5.08(1.83～9.85) 449.89(371.19～560.41) 4.87(4.49～5.39) 1.59(1.25～2.14) 1.26(1.11～1.69) 3.01(2.42～3.85)
治疗后 30 28.06(28.11～34.80) 85.73(82.34～94.47) 0.87(0.84～0.93) 0.67(0.51～0.93) 2.11(1.16～3.51) 17.76(9.01～28.65) 3.31(1.42～5.62) 414.55(297.26～571.31) 4.68(2.41～3.35) 1.37(1.00～2.06) 1.36(1.11～2.01) 2.63(2.32～3.13)
Z值 ? －3.939 －4.331 －3.099 －3.463 －1.223 －1.124 －2.191 －2.459 －0.833 －0.792 －2.767 －1.224
P值 ? <0.001 <0.001 0.002 0.010 0.221 0.261 0.028 0.014 0.405 0.428 0.006 0.221
表5 治疗前、后3组PCOS合并IR患者观察指标差值比较(M±QR)
组别 例数 BMI(kg/m2) 腰围(cm) WHR 睾酮(ng/mL) LH/FSH FINS (mIU/L) HOMA-IR AUCINS (mIU/L) TC (mmol/L) TG (mmol/L) HDL (mmol/L) LDL (mmol/L)
二甲双胍组 30 －1.620±1.610 －3.71±3.00 －0.01±0.02 －0.400±0.430 －1.045±2.520 －2.71±10.30 －0.40±2.06 －125.87±164.90 －0.28±0.75 －0.23±0.62 －0.03±0.05 －0.08±0.47
吡格列酮组 30 0.084±1.970 －3.40±3.75 －0.03±0.03b －0.025±1.630 －0.013±2.450 0.22±22.98 －0.06±6.22 －115.37±95.82 －0.01±0.74 0.16±0.44 0.15±0.34 0.10±0.62
联合组 30 －2.204±2.280a －8.38±6.90 －0.04±0.06b －0.500±1.050 －0.311±2.120 －2.78±8.53 －0.74±2.04 －3.62±295.43 0.06±0.95 －0.17±0.78 0.21±0.21 －0.19±0.56
H值 ? 6.148 1.992 8.459 4.045 1.923 0.013 0.670 0.286 0.163 1.076 0.449 0.195
P值 ? 0.046 0.143 <0.01 0.132 0.382 0.994 0.715 0.752 0.922 0.584 0.640 0.824
表6 3组PCOS合并IR患者治疗后2个月经周期BBT双相率和妊娠率比较[例数(%)]
组别 例数 2个月经周期BBT双相率 妊娠率
二甲双胍组 30 16(56.7) 2 (6.7)
吡格列酮组 30 12(40.0) 6(20.0)
联合组 30 10(33.3) 5(16.7)
χ2值 ? 3.529 2.577
P值 ? 0.171 0.273
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