二甲双胍对多囊卵巢综合征患者纤溶系统、内分泌、代谢的影响及对耐氯米芬的作用

目的：评估二甲双胍对多囊卵巢综合征（PCOS）与耐氯米芬患者的治疗作用。方法：31例PCOS患者（8例为耐氯米芬者）,用二甲双胍375mg/次、3次／d,治疗12－16周,观察服药前后血纤溶酶原激活物抑制物－1（PAI－1）及组织型纤溶酶原激活物（tPA）水平,月经、生殖内分泌激素,糖、脂代谢,卵巢体积的变化及副反应。服用二甲双胍未恢复正常月经、耐氯米芬的患者,再加用氯米芬促排卵,观察排卵情况。非耐氯米芬未恢复正常月经的患者,二甲双胍加量至500mg／次、3次／d,至少8周,观察月经情况。结果：二甲双胍治疗后,PAI－1、黄体生成素／促卵泡激素（LH／FSH）、睾酮、雄烯二酮、低密度脂蛋白胆固醇、总胆固醇、胰岛素、胰岛素曲线下面积、舒张压明显下降,下降幅度分别为3％、41％、25％、34％、28％、14％、27％、23％、7％;左侧卵巢体积缩小59％,右侧卵巢体积缩小41％;雌二醇和FSH水平分别上或42％、58％（P＜0．05－0．01）。二甲双胍375mg/次、3次／d治疗后,61％（19／31）的患者恢复正常月经,2例妊娠;12例恢复正常月经周期,其中6例伴耐氯米芬者再用氯米芬,5例（12／18周期）排卵,2例妊娠,余6例二甲双胍加量至500mg／次、3次／d,1例恢复月经并妊娠。结论：二甲双胍可改善PCOS患者的纤溶系统,生殖内分泌激素,糖、脂代谢,月经失调等,增强耐氯米芬患者对氯米芬的敏感性。

Effects of metformin on the plasminogen activator system, endocrine, metabolic profiles in patients with polycystic ovary syndrome and clomiphene resistant cases

Objective To assess the therapeutic effects of metformin in patients with polycystic ovary syndrome (PCOS) and clomiphene (CC) resistant cases Methods Thirty one patients with PCOS,including 8 CC resistant cases were studied Serum tissue type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI 1), menstrual and reproductive hormone patterns, lipid and glucose metabolic parameters, bilateral ovarian volume, side effects were determined before and after oral administration of metformin 375 mg three times daily for 12-16 weeks Metformin and CC were co administered in CC resistant cases who had not restored their menstrual cycle after the treatment with metformin alone for investigating ovulation rate In the remaining non CC resistant metformin failure cases the dosage of metformin was incrersed to 500 mg three times daily for investigating menstrual cycle Results After administration of metformin for 12-16 weeks, serum PAI 1, luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio, androstenedione, testosterone, low density liproprotein cholesterol, total cholesterol, fasting insulin concentration and response to oral glucose tolerant test (OGTT), diastolic blood pressure decreased significantly, while FSH and estradiol levels increased, bilateral ovarian volume shrunk significantly ( P <0 05-0 01) Body mass index, waist hip ratio,LH, tPA, systolic blood pressure, prolactin, fasting glucose concentration and response to OGTT,high density liproprotein cholesterol, apoliprotein A, apoliprotein B,triglycerides levels did not change significantly ( P >0 05) Nineteen out of thirty one cases (61%) had restoration of menstrual cycle, 2 became pregnant In 6 CC resistant cases who had not restoration of menstrual cycle after the treatment with metformin, CC induced ovulation in 12/18 cycles or 5/6 cases and 2 pregnancies achieved In others 6 metformin failure cases the dosage of metformin was increased to 500 mg three times daily, one restored menstrual cycle and became pregnant Conclusions Metformin may ameliorate the PAI 1, endocrine, metabolic profiles and menstrual abnormalities and improve the ovarian response to CC in CC resistant cases Metformin provides a safe and effective approach to the treatment of PCOS