罗格列酮和二甲双胍治疗胰岛素抵抗多囊卵巢综合征的临床研究

目的　探讨罗格列酮 (rosiglitazone)和二甲双胍 (metformin)分别对有胰岛素抵抗的多囊卵巢综合征(polycysticovarysyndrome,PCOS)患者促排卵治疗的疗效对比。 方法　选择 2 0 0 2年 2月至 2 0 0 3年 6月存在胰岛素抵抗的PCOS患者 94例 ,将其随机分为A、B、C 3组。A组 36例口服罗格列酮联合克罗米芬治疗 ;B组 30例口服二甲双胍联合克罗米芬 (clomiphenecitrate ,CC)治疗 ;C组 2 8例口服克罗米芬治疗。 3组用药时间均为 3个月经周期。比较 3组用药后的胰岛素抵抗指数 (homainsulin resistance ,HomaIR)变化和排卵的发生情况。结果　A组用药 2个月后HomaIR开始由 1 12± 0 4 9下降为 0 86± 0 4 2 ,用药 3个月HomaIR由 1 12± 0 4 9降为0 6 1± 0 36 ,两者比较差异有显著性意义 (P <0 0 5 ) ;B组用药 2个月后HomaIR无明显下降 ,用药 3个月HomaIR由 1 15± 0 5 2降为 0 83± 0 32 ,两者比较差异有显著性意义 (P <0 0 5 )。C组用药前后HomaIR无变化。治疗后 3个月排卵率A组为 76 9% ,明显优于B组的 6 6 8%和C组的 5 8 8% ,差异有显著性意义 (P <0 0 5 )。结论　罗格列酮比二甲双胍能更快更好地改善PCOS的胰岛素抵抗 ,提高促排卵成功率。     

罗格列酮用于多囊卵巢综合征患者促排卵周期的疗效观察

目的：探讨罗格列酮对多囊卵巢综合征有胰岛素抵抗(IR)患者促排卵治疗的效果。方法：将2001年6月至2002年6月81例患者随机分为A、B、C三组，分别给予促排卵药、罗格列酮、罗格列酮与促排卵药合用，比较三组用药前后胰岛素抵抗指数(Homa IR)、游离脂肪酸(FFA)、肿瘤坏死因子(TNFα)和排卵率的变化。结果：罗格列酮治疗前后患者Homa IR指数、血清FFA和TNFα明显下降(P＜0．05)。C组排印卑明显化于A组(P＜0．05)和B组(P＜0．005)。结论：罗格列酮能有效地改善胰岛素抵抗，提高排卵率。     

二甲双胍/CC/HMG序贯用药治疗胰岛素抵抗PCOS患者的临床研究

目的 :探讨二甲双胍对胰岛素抵抗多囊卵巢综合征 (PCOS)患者的治疗效果及作用机理。方法 :随机将 69例胰岛素抵抗PCOS患者分为A、B两组。A组 34例用Diane 35治疗 3个周期后用CC +HMG促排卵 ;B组 35例用二甲双胍治疗 3个月后用CC +HMG促排卵。观察两组患者治疗前后的BMI、T、FINS、TNF α及排卵率。结果 :两组患者治疗后BMI及T差异无显著性(P >0 .0 5) ;FINS、TNF α及排卵率差异有显著性 (P <0 .0 5)。结论 :胰岛素抵抗PCOS患者治疗的关键是应用胰岛素增敏剂降低FINS ,二甲双胍对于PCOS合并不孕的治疗效果优于Diane 35。     

达英-35与胰岛素增敏剂治疗多囊卵巢综合征后促排卵药物的效果观察

目的:探讨比较单独应用达英-35以及达英-35分别与二甲双胍、罗格列酮联合治疗多囊卵巢综合征(PCOS)伴有胰岛素抵抗(IR)不孕患者效果及促排卵结局的差异.方法:97例PCOS伴有IR不孕患者随机分成3组.A组(单独应用达英-35)35例,B组(达英-35和二甲双胍)32例,C组(达英-35和罗格列酮)30例,3组患者治疗3个周期后均促排卵.比较用药后对体重、WHR、BMI、糖代谢、性激素及促排卵结局的影响.结果:3组患者治疗后血清睾酮较治疗前明显降低,B组、c组患者空腹胰岛素,胰岛素抵抗指数等显著下降;治疗后B组、C组妊娠率较A组增高,周期取消率、OHSS发生率较A组降低,差异均有统计学意义.结论:PCOS伴有IR不孕患者应用达英-35联合胰岛素增敏剂(二甲双胍及罗格列酮),可以明显改善内分泌、代谢紊乱,在此基础上促排卵,可以明显提高妊娠率.但因罗格列酮的用药安全性问题及价格较贵,所以此类患者应首选二甲双胍治疗.     

罗格列酮和二甲双胍治疗多囊卵巢综合征患者的临床疗效比较

目的:比较罗格列酮和二甲双胍治疗多囊卵巢综合征的临床疗效。方法:80例氯米芬抵抗的多囊卵巢综合征患者,随机分为罗格列酮组40例和二甲双胍组40例,疗程为6个月,比较两组用药前、后体重指数、月经周期、生殖激素水平、排卵率、妊娠率、血糖和胰岛素水平的变化。结果:①罗格列酮和二甲双胍均可降低血LH/FSH比值和雄激素水平(P<0.05),恢复卵巢排卵功能;②罗格列酮可降低HomaIR指数和Homaβ指数(P<0.05),二甲双胍降低BMI评分(P<0.05)。结论:罗格列酮和二甲双胍均可改善氯米芬抵抗的多囊卵巢综合征患者生育功能;但罗格列酮改善胰岛素抵抗优于二甲双胍,而降低体重作用二甲双胍优于罗格列酮。     

生活方式调整及药物治疗多囊卵巢综合征的临床研究

目的探讨生活方式调整、二甲双胍及罗格列酮治疗多囊卵巢综合征（PCOS）的临床疗效。方法将106例PCOS患者随机分为单纯生活方式调整（锻炼及饮食控制）、生活方式调整＋二甲双胍与生活方式调整＋罗格列酮治疗3组,分别为43、36、27例,共有60例（分别为22、21、17例）患者完成治疗,观察3组患者治疗前、后排卵情况,比较体重指数（BMI）、腰围、腰围与臀围比值（WHR）、血清睾酮、空腹真胰岛素水平、血脂、稳态模型法测定的胰岛素抵抗指数（HOMA-IR）、空腹血糖与胰岛素比值（GIR）、定量胰岛素敏感检测指数（QUICKI）的变化。结果治疗前3组患者年龄、BMI、腰围、WHR、睾酮水平、空腹真胰岛素水平、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白．胆固醇（HDL-C）、低密度脂蛋白-胆固醇（LDL-C）比较,差异均无统计学意义（P〉0．05）。单纯生活方式调整组的43例患者中22例完成治疗,23％（5／22）恢复排卵;生活方式调整＋二甲双胍组的36例患者中21例完成治疗,43％（9／21）恢复排卵;生活方式调整＋罗格列酮组的27例患者中17例完成治疗,59％（10／17）恢复排卵。3组患者的恢复排卵率比较,差异无统计学意义（P〉0．05）;但生活方式调整＋罗格列酮组较单纯生活方式调整组恢复排卵率高,且差异有统计学意义（P〈0．05）。治疗后3组患者的BMI、腰围、WHR、睾酮、TC、TG、LDL-C、HDL-C比较,差异均无统计学意义（P〉0．05）。结论生活方式调整、二甲双胍、罗格列酮对PCOS患者均有恢复排卵作用。     

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     

不同胰岛素增敏剂对多囊卵巢综合征代谢异常的疗效比较

目的:比较二甲双胍与罗格列酮治疗多囊卵巢综合征(PCOS)内分泌、代谢异常的疗效。方法:将89例PCOS患者分成A、B两组,A组予二甲双胍,B组予罗格列酮,均连用6个月。观察患者用药前后的体重、生殖激素、血糖和胰岛素水平的变化。结果:用药6月A组患者体重下降,B组体重上升,两组LH、LH/FSH、T均下降,治疗前后比较差异有显著性(P<0.05);B组T的下降幅度比A组明显(P<0.05)。A、B组空腹胰岛素(FINS)、餐后2小时胰岛素、胰岛素抵抗指数(Homa IR)均下降,治疗前后比较差异有显著性(P<0.05)。FINS、2小时INS以及Homa IR下降程度均表现为:罗格列酮>二甲双胍(P<0.05)。结论:罗格列酮比二甲双胍更能改善PCOS患者的胰岛素抵抗,而且无胃肠副反应,但价格较贵、起效较慢和引起体重增加,而二甲双胍有减轻体重的作用。     

复方环丙孕酮联合罗格列酮、二甲双胍治疗多囊卵巢综合征伴重度胰岛素抵抗疗效观察

目的 探讨复方环丙孕酮(CPA)联合二甲双胍与罗格列嗣,治疗多囊卵巢综合征(PCOS)伴重度胰岛素抵抗(IR)患者内分泌、代谢异常的疗效.方法 2007年1月至2008年6月在哈尔滨医科大学附属第一医院生殖科就诊的84例PCOS伴重度IR患者按不同的治疗方案进行分组,A组33例给予CPA、二甲双胍及罗格列嗣治疗;B组26例给予CPA和罗格列酮治疗;C组25例给予CPA和二甲双胍治疗,疗程为3个月.比较3组患者用药前后的临床表现、性激素、血糖和胰岛素水平的变化.结果 用药3个月A、B、C组血清雄激素水平均较治疗前明显下降,但3者之间无统计学意义(P>0.05),A、B、C 3组治疗后Homa IR、Homaβ、AUCINS均有不同程度下降,B组与C组比较无统计学意义(P>0.05),A组与B、C组比较有统计学意义(P<0.05),Homa、IR、Homa、AUCINS明显改善.结论 对于PCOS合并重度IR的患者,CPA联合二甲双胍和罗格列嗣治疗效果较好,比二甲双胍、罗格列酮分别单独与CPA联合用药有明显的优势.     

罗格列酮用于多囊卵巢综合征促排卵治疗的效果观察

目的　探讨罗格列酮 (rosiglitazone)对存在胰岛素抵抗的多囊卵巢综合征 (polycysticovarysyndrome ,PCOS)患者促排卵治疗的效果。 方法　选择存在胰岛素抵抗的PCOS患者 96例 ,将其随机分为A、B、C组。A组 (2 8例 )口服氯米芬、B组 (3 2例 )口服罗格列酮、C组 (3 6例 )口服罗格列酮联合氯米芬 ,3组用药时间均为 3个月经周期。比较 3组用药前后的胰岛素抵抗指数的变化和排卵情况。结果　B组和C组患者治疗后 ,应用稳态模型评估的胰岛素抵抗指数 (homeostasismodelassessmentinsulinresistance ,HOMAIR)分别由 1 2± 0 6、1 1± 0 5下降为 0 6± 0 2、0 6± 0 4,两组治疗前后比较 ,差异也有显著性 (P <0 0 5)。C组治疗后排卵率为 80 % ,明显高于A组的 59%和B组的 3 5% ,差异有显著性 (P <0 0 5)。结论　罗格列酮能有效地改善胰岛素抵抗 ,提高促排卵治疗的成功率     

Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity

OBJECTIVE: To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone. DESIGN: Randomized controlled double-blind trial. SETTING: A referral center in Caracas, Venezuela. PATIENT(S): One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention. INTERVENTION(S): One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo. MAIN OUTCOME MEASURE(S): Frequencies of ovulation and serum free T after 6 months. RESULT(S): Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone. CONCLUSION(S): These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.     

糖尿病家族青春期多囊卵巢综合征胰岛素抵抗的临床特征和治疗

目的:探讨糖尿病(DM)家族青春期多囊卵巢综合征(PCOS)胰岛素抵抗(IR)的程度及应用二甲双胍治疗的效果。方法:选择父亲或母亲被确诊患DM的7例青春期PCOS患者为实验组,以无DM家族史的28例青春期PCOS患者为对照组。测体重指数(BM I)、基础体温(BBT),抽血测FSH、LH、PRL、T、E2、P,行75g葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT)。计算空腹血糖胰岛素比率(FGIR)、糖负荷120m in血糖胰岛素比率(G120/I120)及稳态模型的胰岛素抵抗指数(HOMA-IR)。确诊IR患者进行包括二甲双胍在内的综合治疗,每3月重复检测1次上述指标。结果:实验组7例均超重(BM I≥25),其比率明显高于对照组(7/7vs12/28,P<0.01);实验组IR患病率亦明显高于对照组(7/7vs 9/21,P<0.01),且IR程度明显高于对照组IR患者(HOMA-IR为14.35vs 6.02,P<0.01)。两组接受二甲双胍综合治疗的IR患者治疗6月后空腹胰岛素(I0)比治疗前明显降低(32.47vs 40.36,P<0.05),胰岛素敏感性(IS)明显提高(FGIR为3.42 vs2.99,P<0.05),T降低,并有3例卵巢恢复排卵。结论:DM家族青春期PCOS患者可能存在较重IR,坚持二甲双胍综合治疗可减轻IR程度并恢复卵巢排卵功能。     

Metformin versus rosiglitazone in the treatment of polycystic ovary syndrome

OBJECTIVE: The aim of our study is to investigate and compare the clinical, biochemical and hormonal changes during application of insulin-sensitizers from two different groups. STUDY DESIGN: This prospective, open clinical study lasted 3 months and included 30 women with PCOS, divided in two groups of 15 women each. Group 1 received 850 mg metformin twice a day and group 2 was treated with rosiglitazone 4 mg a day. Serum levels of testosterone, immune reactive insulin (IRI), sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS) and lipid metabolism parameters were measured before the treatment, and on the 3rd month. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Two parameters change significantly in the 3rd month in our study--testosterone and insulin. Much better decrease in the level of testosterone and free androgen index was established in group treated with metformin, while the indices of insulin resistance were better influenced in the group treated with rosiglitazone. CONCLUSION: Application of insulin sensitizers from both groups has a favorable influence on the basic hormonal deviations in PCOS--the hyperandrogenemia and the insulin resistance. In cases with PCOS metformin treatment influences better hyperandrogenemia, while rosiglitazone affects more pronouncedly insulin resistance and hyperinsulinemia.     

二甲双胍和噻唑烷二酮类分别与达因-35联用治疗多囊卵巢综合征的疗效比较

目的:比较二甲双胍和噻唑烷二酮类(TZDs)分别与达因-35联用治疗多囊卵巢综合征(PCOS)的临床疗效。方法:随机将53例患者分成两组,A组予以二甲双胍治疗3个月后与达因-35共用3个月,B组予以TZDs治疗3个月后和达因-35共用3个月,总治疗期6个月,比较治疗前后内分泌激素、体重指数、血糖、排卵率等的改变。结果:两组治疗后胰岛素(INS)、胰岛素抵抗指数(HOMA-IR)、甘油三酯(TG)、低密度脂蛋白(LDL-C)、睾酮(T)及黄体生成素(LH)均明显降低(P<0.05,P<0.01)。A组降低体重优于B组,B组改善胰岛素抵抗优于A组。两组在排卵率和妊娠率方面无显著差异(P>0.05),双胍组4例自发性妊娠,TZDs组也有4例自发性妊娠。随访1年,8例婴儿发育均无异常。结论:二甲双胍和TZDs分别与达因-35联用,均能改善PCOS患者的胰岛素抵抗及内分泌紊乱,肥胖的PCOS患者推荐首选二甲双胍+达因-35,体重正常者或胰岛素抵抗严重者选用TZDs+达因-35。     

The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to assess the effects of metformin and rosiglitazone on menstrual cyclicity and hirsutism in patients with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Ninety-six patients were included in the study. Serum sex steroids, serum fasting glucose and insulin levels, and insulin response to a 75-g oral glucose tolerance test were assessed in all patients. Menstrual cyclicity, with recording of menses in the 6-month periods before the study and during treatment, was evaluated in each patient. Patients were divided into two groups: one was treated with metformin (MET group, n = 48), while the other received rosiglitazone (ROSI group, n = 48). At baseline and after 24 weeks of treatment all patients underwent hormonal and clinical assessments, including body mass index (BMI), waist and hip measurements and Ferriman - Gallwey (FG) scores. RESULTS: Of the 96 patients included in the study, 88 (91.7%) were able to complete it and yielded data for analyses. After the 24-week treatment period, fasting insulin levels and area under the curve for serum insulin decreased significantly, while the glucose/insulin ratio increased in both groups. The degree of reduction in serum free testosterone and androstenedione levels was similar in the two groups. The decreases in luteinizing hormone/follicle-stimulating hormone ratio and serum dehydroepiandrosterone sulfate levels were significantly greater in the ROSI group compared with the MET group. BMI increased in the ROSI group, while it decreased in the MET group. In patients with menstrual disturbance treated with rosiglitazone, menstrual cycles became regular in 87.8%, while improvement occurred in 79.3% of the patients treated with metformin. FG score decreased in both ROSI and MET groups, but the degree of decrease was significantly greater in the ROSI group than in the MET group. CONCLUSION: Our data show that both metformin and rosiglitazone improve ovarian function and hirsutism in patients with PCOS. Rosiglitazone appears better than metformin in the treatment of hirsutism and has better patient tolerance.     

二甲双胍治疗耐克罗米酚多囊卵巢综合征23例临床分析

目的探讨二甲双胍在多囊卵巢综合征(PCOS)治疗中的作用.方法对23例耐克罗米酚PCOS患者的临床资料进行回顾性分析,比较二甲双胍治疗前后各项内分泌代谢指标的变化及其对恢复月经、促排结局及妊娠的影响.结果二甲双胍治疗前后比较,血清睾酮、空腹胰岛素水平下降,胰岛素敏感性指数上升(P<0.01).6例(26.09%)的患者恢复月经,4例(17.39%)恢复自然排卵,2例妊娠. 二甲双胍加促排治疗共26个周期,排卵周期率为61.54%(16/26),妊娠周期率为23.08%(6/26). 结论二甲双胍可以降低雄激素水平及胰岛素水平,改善PCOS妇女对克罗米酚促排的反应.