二甲双胍对多囊卵巢综合征患者胰岛素样生长因子-1的影响

目的探讨二甲双胍对多囊卵巢综合征（PCOS）患者血清胰岛素样生长因子-1（IGF-1）及胰岛素样生长因子结合蛋白-1（IGFBP-1）水平的影响及其作用机制，明确二甲双胍治疗的临床效果。方法2002年1—11月对山西医科大学第二医院24例PCOS患者给予二甲双胍500mg，一日3次，8～24周治疗，比较治疗前后血清IGF-1、IGFBP-1、空腹胰岛素及睾酮水平，并对月经恢复、排卵、妊娠情况进行分析。结果二甲双胍可降低血清空腹胰岛素及睾酮水平，能显著升高IGFBP-1水平，治疗前后血清IGF—1水平差异无显著性。单纯二甲双胍治疗后月经恢复率为41．67％（10／24）；自然排卵率为25．00％（6／24），自然妊娠率为12．50％（3／24）。二甲双胍加促排卵治疗共18个周期，排卵周期率66．67％（12／18），妊娠周期率为11．11％（2／18）。结论二甲双胍可以降低血清空腹胰岛素及睾酮水平，增高IGFBP-1水平，可以改善卵泡微环境，有助于月经恢复，提高促排卵和妊娠率．是治疗PCOS的重要手段。     

二甲双胍在多囊卵巢综合征促排卵治疗中的作用

目的　评估二甲双胍在多囊卵巢综合征 (PCOS)患者促排卵治疗中的作用。方法　以40例PCOS患者 (PCOS组 )为研究对象 ,其中 2 0例口服二甲双胍治疗 12周 ,治疗后 17例未孕者加用高纯度促卵泡激素 (FSH HP)治疗 1个周期 (A组 ) ,另 2 0例单用FSH HP治疗 1个周期 (B组 ) ;同时 ,以体重和月经周期均正常的 2 0例门诊患者为对照组。观察各组及A组患者口服二甲双胍前后血清FSH、黄体生成激素 (LH)、睾酮、瘦素、空腹血糖及空腹胰岛素水平 ;比较A、B两组促排卵治疗结果。结果　空腹胰岛素和瘦素水平 ,PCOS组显著高于对照组 (P <0 .0 5) ,PCOS肥胖者高于PCOS非肥胖者(P <0 .0 5) ,但PCOS非肥胖者与对照组相比 ,差异无显著性 (P >0 .0 5)。二甲双胍治疗后 ,LH、空腹胰岛素、睾酮及瘦素水平明显下降 (P <0 .0 5～ 0 .0 1)。PCOS组患者中有 3例服二甲双胍治疗期间妊娠 ,另外 3 7例行FSH HP促排卵治疗后有 7例妊娠 (A组 4例 ,B组 3例 ) ,总妊娠率为 19% ( 7 3 7) ;A组的排卵率 ( 88% ,15 17)和妊娠率 ( 2 4% ,4 17)虽高于B组 ( 70 % ,14 2 0 ;15% ,3 2 0 ) ,但差异无显著性 (P >0 .0 5)。结论　二甲双胍能降低胰岛素和瘦素水平 ,逆转PCOS患者性激素异常 ,使部分患者恢复排卵和妊娠 ,可增强PCOS患者对促性腺素的敏感     

二甲双胍在多囊卵巢综合征的应用

胰岛素抵抗是多囊卵巢综合征(PCOS)的重要病理生理改变,应用二甲双胍治疗PCOS患者可以改善月经状况,恢复排卵,并且增加不孕PCOS患者的妊娠率,对提高IVF的成功率和减少反复流产的发生也非常有益。本文对二甲双胍作用机制,二甲双胍对PCOS及不孕的PCOS患者的治疗作用进行了综述。     

二甲双胍治疗多囊卵巢综合征新进展

多囊卵巢综合征(PCOS)是生育年龄妇女常见的生殖内分泌疾病.由于胰岛素抵抗在其发病中起重要作用,胰岛素增敏剂二甲双胍被用于PCOS的治疗.随着临床的广泛应用,对其作用机理和临床效果有了更深入的认识.二甲双胍可以恢复规律月经,改善多毛,降低体质量,促进排卵,改善妊娠结局,改善子宫内膜的胰岛素抵抗,避免远期并发症,特别是对青春期PCOS患者有较好的疗效.不同剂量的二甲双胍具有不同的治疗作用.对二甲双胍在治疗PCOS中的新进展做.     

二甲双胍联合炔雌醇环丙孕酮在多囊卵巢综合征治疗中的应用价值

目的 探讨多囊卵巢综合征患者采用二甲双胍联合炔雌醇环丙孕酮治疗的临床效果。方法 选取60例多囊卵巢综合征患者,根据信封法分为两组,每组30例。对照组给予炔雌醇环丙孕酮治疗,研究组在对照组基础上联合二甲双胍治疗。比较两组治疗前后的性激素水平、胰岛素水平、月经规律恢复及排卵恢复情况。结果 治疗后研究组睾酮(T)、卵泡刺激素(FSH)、雌二醇(E₂)、促黄体生成素(LH)水平均低于对照组(P<0.05)。治疗后研究组空腹胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR)低于对照组,胰岛素分泌指数(HOMA-β)高于对照组(P<0.05)。研究组月经规律恢复率93.33%高于对照组的73.33%,排卵恢复正常率96.67%高于对照组的80.00%(P<0.05)。结论 炔雌醇环丙孕酮联合二甲双胍能改善多囊卵巢综合征患者性激素、胰岛素水平,促进患者月经规律和排卵恢复,值得临床推广与应用。     

二甲双胍联合吡格列酮治疗多囊卵巢综合征临床观察

目的观察联合应用二甲双胍和吡格列酮对多囊卵巢综合征(PCOS)的治疗效果.方法选择具有胰岛素抵抗的PCOS患者30例,给予二甲双胍500 mg,每日2次和吡格列酮15 nag,每日1次,治疗6个月.检测患者治疗前、后和停药6个月的血清性激素水平和胰岛素释放水平.结果15例多毛、痤疮症状均明显改善.22例(78.6%)恢复规律的排卵性月经.治疗后黄体生成激素(LH)、睾酮(T)、空腹胰岛素(F-Ins)、胰岛素曲线下面积(Ins-Auc)均分别下降,与治疗前相比,差异有非常显著性,P＜0.01.但在停药6个月内,15例已恢复排卵性月经的患者又相继停经,LH、T、F-Ins、Ins-Auc又有所上升,但与治疗前相比,差异无显著性(P＞0.05).结论二甲双胍联合吡格列酮对治疗PCOS具有协同作用,是一种安全且有效的的方法,但在停药后病情有一定程度的复发.     

二甲双胍治疗高胰岛素血症所致无排卵的临床观察

目的了解高胰岛素对血睾酮水平和排卵功能的影响,二甲双胍治疗高胰岛素血症无排卵的临床效果.方法对29例高胰岛素血症患者,进行12周的二甲双胍治疗,其中19例在二甲双胍治疗前后均接受氯米芬治疗1个周期.观察治疗前后血睾酮水平和排卵功能的变化.结果二甲双胍治疗前血睾酮水平为(2.7±1.6)nmol/L,治疗4周后为(1.9±1.0)nmol/L,两者比较,差异有显著性(P＜0.05).自发排卵,二甲双胍治疗前有3例,治疗后有10例(其中8例为原无排卵者)(P＜0.05);19例在二甲双胍治疗前后均服用过氯米芬,促排卵成功在二甲双胍治疗前有8例、治疗后有15例(P＜0.05).结论高胰岛素血症可引起血睾酮水平升高,排卵功能障碍.应用二甲双胍后胰岛素水平降低,睾酮水平下降,排卵功能有改善.     

吡格列酮联合二甲双胍治疗多囊卵巢综合征伴胰岛素抵抗的疗效观察

目的观察吡格列酮联合二甲双胍治疗多囊卵巢综合征(PCOS)伴胰岛素抵抗(IR)的疗效。方法选取2012年3月~2014年9月我院收治的PCOS伴IR患者72例,将其随机分成观察组与对照组,各36例。观察组给予吡格列酮联合二甲双胍片治疗,对照组给予二甲双胍治疗。3月后,观察两组患者的疗效。结果观察组患者接受治疗后空腹胰岛素(F-INS)、黄体生成素(LH)、睾酮(T)等指标均明显低于治疗前,且均明显高于观察组,月经不规律人数减少,恢复排卵人数增加,差异有统计学意义(P0.05)。结论吡格列酮联合二甲双胍片治疗PCOS具有良好的疗效,能更好地改善机体激素水平,增加胰岛素敏感性,恢复排卵,值得临床推广。     

二甲双胍对PCOS合并高胰岛素血症患者血清胰岛素及性激素的影响

目的:探讨二甲双胍对多囊卵巢综合征(PCOS)合并高胰岛素血症患者血清胰岛素、性激素及性激素结合球蛋白(SHBG)水平的影响及其作用机制,了解二甲双胍治疗的临床效果。方法:给予2 4例PCOS合并高胰岛素血症患者二甲双胍5 0 0mg ,每日3次,8周治疗,对治疗前后血清空腹胰岛素(FINS)、胰岛素敏感性指数、性激素及性激素结合球蛋白水平进行检测。结果:二甲双胍可降低血清空腹胰岛素及睾酮水平(P <0 .0 1) ,提高胰岛素敏感性指数(P <0 .0 1) ,治疗前后血清SHBG水平差异无显著性(P >0 .0 5 )。结论:二甲双胍是治疗PCOS的重要手段。     

炔雌醇环丙孕酮联合二甲双胍治疗多囊卵巢综合征的临床效果观察

目的 观察炔雌醇环丙孕酮联合二甲双胍治疗多囊卵巢综合征（PCOS）的临床效果。方法 选取90例PCOS患者,按照随机数字表法分为研究组（采用炔雌醇环丙孕酮联合二甲双胍治疗）与对照组（采用炔雌醇环丙孕酮治疗）,每组45例。比较两组治疗前后激素水平、排卵率及妊娠率。结果 治疗前,两组卵泡刺激素（FSH）、促黄体生成素（LH）、睾酮（T）、胰岛素水平对比,差异均无统计学意义（P>0.05）;治疗后,两组LH、T及胰岛素水平均有所降低,FSH水平升高,其中研究组变化幅度大于对照组,差异有统计学意义（P<0.05）。研究组排卵率、妊娠率分别为84.44%、37.78%,均明显高于对照组的53.33%、17.78%,差异有统计学意义（P<0.05）。结论 炔雌醇环丙孕酮联合二甲双胍治疗POCS疗效更佳,可有效纠正患者内分泌紊乱,降低LH、T和胰岛素水平,提高FSH水平,促进卵泡发育,从而提高患者排卵率、妊娠率。     

二甲双胍治疗耐克罗米芬的多囊卵巢综合征40例分析

目的：观察二甲双胍单用或联合高纯度卵泡刺激素（metrodin-HP即FSH－HP）治疗耐克罗米芬（CC)多囊卵巢综合征（PCOS）患者的疗效。方法：选择耐CC的PCOS患者40例，随机分成A组和B组。A组：20例患者从卵泡早期开始服二甲双胍，每天1500mg共12周，若未孕则加FSH－HP促排卵1个周期，B组；20例患者单独用FSH－HP促排卵1个周期。测定所有患者的性激素、空腹血糖（FG）及空腹胰岛素（FINS）。结果：服二甲双胍后，LH、T及FINS的水平明显下降（P＜0．05），A组有7例患者排卵且3例妊娠，妊娠率为15．0％，17例未孕者继续服二甲双胍联合FSH－HP促排卵，15例排卵和4例妊娠，妊娠率23．5％，B组单用FSH－HP促排卵，有14例排卵且3例妊娠，妊娠率15．0％，两者的妊娠率差异无显著性意义（P＞0．05）。A组的FSH－HP用量少于B组，差异有显著性意义（P＜0．05），中度以上OHSS发生率分别为0和10％，前者的发生率低于后者（P＜0．05）。结论：单用二甲双胍能使部分患者恢复排卵和妊娠。FSH－HP联合二甲双胍能减少FSH－HP的用量和OHSS的发生。二甲双胍单用或联合FSH－HP促排卵为耐CC的PCOS患者找到一种有效的治疗方法。     

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC?+?MET, or LE and LE?+?MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.     

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。     

Metformin improves ovulation and pregnancy rates in patients with polycystic ovary syndrome

We evaluated the fertility promoting effect of metformin in infertile patients with polycystic ovary syndrome. Twenty-nine infertile patients with polycystic ovary syndrome (PCOS) are included in our prospectively designed study and 15 normal menstruating women served as controls for reproductive hormones and ovarian volumes. All PCOS patients received a total of 78 cycles of clomiphene citrate (CC) in the beginning, then patients who could not get pregnant were switched to metformin plus clomiphene citrate. PCOS patients served as their own controls for the ovulation and pregnancy rates. At the end of the CC cycles 4.2% of patients got pregnant and 65.2% of the remaining group got pregnant with metformin plus CC cycles (p=0.0001). We have not observed any serious side effects of metformin. The high pregnancy rate of our study population is consistent with the hypothesis that insulin resistance plays an important role in the pathogenesis of anovulation in patients with PCOS.     

Metformin versus laparoscopic unilateral ovarian drilling in clomiphene resistant women with polycystic ovary syndrome

ObjectivesTo compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin and women undergoing unilateral ovarian drilling in clomiphene citrate(CC) resistant patients with polycystic ovary syndrome (PCOS)DesignNon randomized controlled trial.SettingObstetrics and Gynecology department, Faculty of medicine, Zagazig University, Egypt.MethodsA total of 120 patients were divided into group 1(n=58) who received metformin therapy and group 2 (n=62) who underwent unilateral ovarian drilling. Hormonal-metabolic profiles changes after treatment were reported and reproductive outcomes were compared between both groups.Main outcomeFSH and LH were reduced significantly in unilateral drilling group (P=<0.001and 0.001), while there was significant improvement in testosterone level , fasting insulin, fasting glucose to insulin ratio and homeostasis model assessment index in metformin therapy group. Pregnancy and ovulation rates were higher after unilateral drilling with significant difference (P=0.048 and 0.004). No significant difference in early miscarriage rate between both groups (P=0.51).ConclusionUnilateral LOD was associated with greater ovulation and pregnancy rates than metformin in women with PCOS who did not conceive with CC.     

Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Infertility clinic of a tertiary referral center. PATIENT(S): Fifty-six women with clomiphene citrate-resistant PCOS. INTERVENTION(S): Two cycles of oral metformin therapy (850 mg, twice daily) in group I and placebo therapy (twice daily) in group II. Clomiphene citrate (100 mg/day) on cycle days 3-7 of the second cycle in both groups. MAIN OUTCOME MEASURE(S): Insulin, T, DHEAS, FSH, LH, body mass index (BMI), waist-to-hip ratio, endometrial thickness, cervical score, ovulation, and pregnancy rates in clomiphene-induced cycles after metformin therapy. Result(s): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI. No difference in waist-to-hip ratio, DHEAS level, and fasting insulin level was observed. Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group. There was higher cumulative pregnancy rate in the metformin group; however, there was no significant difference in the pregnancy rate between the two groups. CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS.     

Effects of low-dose metformin in Japanese women with clomiphene-resistant polycystic ovary syndrome

Background and Aims  The aim of the present prospective observational study was to evaluate the effects of low-dose, short-term metformin, in combination with domiphene (CC), in CC-resistant infertile Japanese women with polycystic ovary syndrome (PCOS). Methods  Metformin therapy was administered orally (one 250 mg tablet, twice daily) to 15 CC-resistant infertile patients with PCOS, beginning on the third day of progestin-induced withdrawal bleeding, and was continued for 14 days in the first cycle. In the event of anovulation, 100 mg/day of CC was given during subsequent cycles on days 5–9, in addition to the aforementioned dose of metformin. Hormonal and metabolic parameters were measured on the second or third days of the first cycle and also the fourth cycle, following an overnight fast. Results  None of the 15 women successfully ovulated during the first cycle with metformin treatment alone. After two subsequent cycles with the combination of CC and metformin, ovulation was confirmed in 17 of 29 cycles (61%) and in 13 of 15 patients (87%). Two women became pregnant within 2 months of therapy (13%). There were no cases of ovarian hyperstimulation syndrome. Following three cycles of metformin therapy, a slight reduction in serum levels of luteinizing hormone (LH), free testosterone, androstenedione, dehydroepiandrosterone sulfate, hemoglobin Alc and total cholesterol was seen, while serum LH/follide-stimulating hormone ratio and serum level of low-density lipoprotein cholesterol were significantly decreased. Although there were no significant differences between the responder (n = 11) and non-responder (n = 2) groups at baseline, the levels of plasma fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the non-responder group compared with the responder group after three cycles. Conclusion  Low-dose, short-term metformin, combined with CC, can improve ovulation rates in CC-resistant infertile Japanese women with PCOS.     

Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone

OBJECTIVE: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.     

The role of metformin in ovulation induction: Current status

To define the exact role of metformin in ovulation induction, it is crucial to distinguish three different indications: naïve PCOS, CC-resistant PCOS and ART. In naïve PCOS: metformin as compared to placebo has been shown to improve ovulation rates, but metformin did not exert significant advantage over CC with respect to cumulative ovulation, pregnancy or live-birth rates. The combined approach of metformin plus CC is not better than CC or metformin monotherapy in naïve PCOS. In CC-resistant patients: metformin has no benefit over placebo in ovulation, pregnancy, and live-birth rates as a single agent, but the combination of metformin and CC significantly improved ovulation and pregnancy rates when compared with CC alone. However, combined therapy did not improve the odds of live birth. Metformin pretreatment improves the efficacy of CC in PCOS patients with CC resistance. In PCOS patients scheduled for ART: metformin addition to gonadotropins reduces the duration of gonadotropins administration and the doses of gonadotropins required, and increases the rate of monoovulations, reducing the risk of cancelled cycles. Metformin co-administration to IVF treatment does not improve pregnancy or live-birth rates but reduces the risk of OHSS.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.