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。     

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.     

Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome

OBJECTIVE: In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Academic reproductive endocrinology clinic. PATIENT(S): Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC. INTERVENTION(S): Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months. MAIN OUTCOME MEASURE(S): The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens. RESULT(S): Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change. CONCLUSIONS: Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.     

Insulin-lowering drugs in polycystic ovary syndrome

The discovery that insulin resistance has a key role in the pathophysiology of PCOS has led to a novel and promising form of therapy in the form of the insulin-sensitizing drugs. Although no extremely large trials using these drugs for this indication have been performed, more than 18 trials have specifically examined the effects of these drugs on ovulation, hyperandrogenemia, and dysmetabolic features in PCOS. Table 1 summarizes the results of previous trials using each of the insulin-sensitizing drugs discussed herein. Among the various agents (i.e., thiazolidinediones, [table: see text] metformin, and D-chiro-inositol), metformin is the most widely tested. Metformin may have the added benefit of improving at least some features of syndrome X, such as hypertension and obesity. All of the evidence to date suggests that metformin is a safe drug to administer to women who may become pregnant. In contrast, the two thiazolidinediones currently available, rosiglitazone and pioglitazone, are category C drugs that have been demonstrated to retard fetal development in animal studies. Overall, insulin-sensitizing therapy presents a promising and unique therapeutic intervention for the treatment of PCOS, offering metabolic and gynecologic benefits for women who sustain this syndrome.     

Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling

AIM: To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). METHODS: Forty-two infertile women with PCOS were selected in this randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were randomly divided into group 1 (n = 21) and group 2 (n = 21). Group 1 patients were treated with laparoscopic ovarian drilling (LOD). Group 2 patients underwent laparoscopic ovarian drilling (LOD) and received 1700 mg per day of metformin for 6 months. LOD was performed in women with PCOS using a unipolar electrode. Serum progesterone (P) level > 5 ng/mL was considered as a confirmation of ovulation. Ovulation and pregnancy rates were determined after six cycles. RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD (34.6 +/- 25.4 ng/mL, 8.4 +/- 1.1 mm) than in those treated with LOD alone (26.2 +/- 24.7 ng/mL, 7.9 +/- 2.8 mm) (P < 0.05). The ovulation (56 of 65 cycles, 86.1% vs 29 of 65 cycles, 44.6%) and pregnancy rates (nine of 21 women, 47.6% vs four of 21 women, 19.1%) were significantly higher in group 2 than in group I. CONCLUSIONS: Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.     

Treatment with flutamide improves hyperinsulinemia in women with idiopathic hirsutism.

OBJECTIVE: To investigate insulin metabolism and its modifications induced by the administration of flutamide, a specific antiandrogen compound, in women with idiopathic hirsutism (IH) and in nonobese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Caligari, Caligari, Italy. PATIENT(S): Thirty-two women with normal body mass index participated in the study: 11 with clinical and hormonal features of PCOS and 21 age- and weight-matched normally cycling women with IH (n = 11) and without IH (n = 10, controls). INTERVENTION(S): Each subject with PCOS or IH was assigned randomly to receive either flutamide tablets (250 mg twice a day) or placebo for > or =5 months. Twelve subjects (6 with PCOS, 6 with IH) received flutamide and 10 (5 with PCOS, 5 with IH) received placebo. All subjects ingested 75 g of glucose and then underwent an oral glucose tolerance test (OGTT), 3-7 days after spontaneous or medroxyprogesterone acetate (5 mg daily for 5 days)-induced menses. In women with PCOS or IH, the OGTT was repeated at the fourth month of treatment. MAIN OUTCOME MEASURE(S): Fasting and OGTT-stimulated levels of glucose, insulin, and C peptide. RESULT(S): Both fasting and OGTT-stimulated levels of insulin and C peptide were significantly higher in women with PCOS and in those with IH than in controls. Placebo did not modify parameters of glucose metabolism. Flutamide was capable of significantly blunting fasting and OGTT-stimulated secretion of insulin only in women with IH. CONCLUSION(S): Hyperinsulinemia exists in women with IH as well as in nonobese women with PCOS. Treatment with flutamide can completely reverse hyperinsulinemia only in women with IH, which suggests that the efficacy of the drug is dependent on peripheral androgen hyperactivity.     

Adiponectin levels in women with polycystic ovary syndrome and severe insulin resistance

OBJECTIVE: Adiponectin is an adipokine that is decreased in obesity and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are obese and are at risk for type 2 diabetes. The objective of the current study was to investigate the relationship of adiponectin to obesity and insulin resistance in women with PCOS and severe insulin resistance. METHODS: Thirty women with PCOS and acanthosis nigricans indicating severe insulin resistance were included in the study. Eleven body mass index (BMI)-matched women with normal ovulatory cycles served as controls. Fasting glucose, insulin, and adiponectin levels were measured, and a standard oral glucose tolerance test (OGTT) with insulin levels was performed. To further investigate the role of insulin sensitivity on adiponectin levels, 10 women with PCOS were treated with 4 mg rosiglitazone daily for 6 months and adiponectin levels were measured before and after treatment. RESULTS: Fasting insulin levels (33.5 +/- 3.8 microU/mL; P <.001) and insulin area under the curve (AUC) during OGTT (536.2 +/- 70.5 microU/mL; P <.01) were higher in women with PCOS, while glucose levels were similar to controls. Adiponectin levels were lower (P <.01) in women with PCOS (5.6 +/- 2.6 microg/mL) compared with controls (8.5 +/- 3.9 microg/mL). There was a significant negative correlation between adiponectin levels and fasting insulin levels (r = -0.40, P = .02), insulin AUC during OGTT (r = -0.47, P = .008), fasting glucose levels (r = -0.45, P = .01), and glucose AUC during OGTT (r = -0.51, P = .003). There was no correlation between BMI and serum adiponectin (r = -0.12, P = .508) in women with PCOS, while there was a negative correlation (r = -0.746, P = .013) in controls. There was a significant (P <.01) increase in adiponectin levels when treated with rosiglitazone, despite unchanged BMI. CONCLUSION: These results indicate that in women with PCOS and severe insulin resistance, insulin sensitivity appears to be the major determinant of adiponectin levels rather than adiposity. Low adiponectin levels may predict women with PCOS who are at high risk for developing type 2 diabetes.     

Metformin versus flutamide in the treatment of metabolic consequences of non-obese young women with polycystic ovary syndrome: a randomized prospective study.

In addition to the reproductive consequences, polycystic ovary syndrome (PCOS) is characterized by a metabolic disorder in which hyperinsulinemia and insulin resistance are central features. The effects and possible benefits from insulin-sensitizing drugs are not well known, especially in non-obese women with PCOS. This study was designed to evaluate the effects of metformin and flutamide on metabolic parameters and insulin resistance in non-obese women with PCOS. Thirty non-obese women newly diagnosed with PCOS and 15 age- and weight-matched healthy volunteers as controls were included in the study. Patients were assigned randomly to receive flutamide 250 mg daily or metformin 850 mg three times daily. Glucose, insulin, insulin resistance, androgen levels and glucose and insulin responses to an oral glucose tolerance tests (OGTT) were assessed before and after a 4-week therapy period. A positive correlation was found between body mass index and insulin level in patients with PCOS and controls. Follicle stimulating hormone, luteinizing hormone, free testosterone and dehydroepiandrosterone sulfate levels decreased significantly, but insulin resistance levels were not changed after flutamide therapy. Body weight, free testosterone, insulin and insulin resistance levels decreased significantly after metformin therapy. In conclusion, metformin treatment improved insulin sensitivity and decreased androgen levels, and flutamide decreased androgen levels but failed to improve insulin sensitivity in the non-obese women with PCOS.     

罗格列酮联合二甲双胍治疗多囊卵巢综合征的临床疗效观察

目的 :探讨罗格列酮联合二甲双胍治疗多囊卵巢综合征 (PCOS)的临床疗效。方法 :10 0例临床上有PCOS表现的肥胖不育患者通过口服葡萄糖耐量试验 (OGTT)、胰岛素及C肽释放试验 ,检出胰岛素抵抗 (IR)患者 80例 ,随机分为A、B、C 3组 ,分别给予促排卵药 ,促排卵药加二甲双胍 ,促排卵药加二甲双胍加罗格列酮 ,共治疗 2个月经周期 ,比较 3组用药前后及 3组间体重指数 (BMI)、胰岛素抵抗指数 (HomaIR)、游离脂肪酸(FFA)、肿瘤坏死因子α(TNFα)、纤溶酶原激活抑制物 1(PAI 1)和排卵率的变化。结果 :C组患者治疗后的BMI、HomaIR、FFA、TNFα、PAI 1较治疗前明显下降 (P <0 .0 5 )。C组的排卵率明显优于A组 (P <0 .0 1)和B组 (P <0 .0 5 )。结论 :罗格列酮联合二甲双胍治疗PCOS效果显著。     

A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study

OBJECTIVE: To obtain data from a pilot randomized trial on the effect of metformin therapy and lifestyle modification on ovulation and androgen concentrations in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, placebo-controlled pilot trial. SETTING: Academic medical center. PATIENT(S): Thirty-eight overweight or obese women with PCOS. INTERVENTION(S): All subjects were randomized to one of four 48-week interventions: metformin 850 mg two times per day, lifestyle modification plus metformin 850 mg two times per day, lifestyle modification plus placebo, or placebo alone. MAIN OUTCOME MEASURE(S): Recruitment, dropout, and compliance with a long-term lifestyle intervention in PCOS; preliminary estimates of treatment effect on ovulation, as measured by weekly urinary pregnanediol glucuronide, and on total T and free androgen index. RESULT(S): It was necessary to screen seven women to have one subject randomized. The dropout rate was 39%, with the majority of dropouts occurring within the first 24 weeks. Mean body mass index was >39 mg/kg(2). Modest weight reduction was found in all treatment groups, with the most significant reduction occurring with the combination of metformin and lifestyle intervention. Significant androgen reduction occurred in the combination group only. Ovulation rates did not differ significantly between groups. However, when data were analyzed by presence or absence of weight reduction in subjects, independent of treatment group, the estimated odds ratio for weight loss was 9.0 (95% confidence interval 1.2-64.7) with respect to regular ovulation. If weight loss occurred during metformin therapy, the odds ratio for regular ovulation was 16.2 (95% confidence interval 4.4-60.2). CONCLUSION(S): Key methodologic issues for a large-scale, randomized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity. Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS.     

Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin

OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Gynecology of Federal University of S?o Paulo, S?o Paulo, Brazil. PATIENT(S): Twenty-nine patients with PCOS. INTERVENTION(S): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months. MAIN OUTCOME MEASURE(S): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment. RESULT(S): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2). CONCLUSION(S): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen.     

Metformin therapy in the management of polycystic ovary syndrome: endocrine,metabolic and reproductive effects

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. Impairment in insulin metabolism is a prominent feature of the syndrome and appears to play a key pathogenetic role precipitating the cascade of other disorders associated with PCOS. Recent studies report that insulin-sensitizing agents ,such as metformin ,reduce hyperinsulinemia ,reverse the endocrinopathy of PCOS and normalize endocrine ,metabolic and reproductive functions ,leading to the resumption of menstrual cyclicity and ovulation. In this review ,we report the most recent evidence regarding metformin usage in women with PCOS.     

Insulin resistance in nonobese Japanese women with polycystic ovary syndrome is associated with poorer glucose tolerance,delayed insulin secretion,and enhanced insulin response

PurposeTo determine the prevalence of insulin resistance (IR) and impaired glucose tolerance (IGT) in PCOS patients, the optimal screening method, and to compare our findings between nonobese and obese Japanese women with PCOS.MethodsNinety‐eight PCOS patients were included in this research from 2006 to 2013. Glucose tolerance test (OGTT) was performed. Serum glucose and insulin concentration were assayed before and 30, 60, and 120 min after taking 75 g of glucose.ResultsAll examined metabolic parameters were significantly favorable in the nonobese subjects, below 25 kg/m². HOMA‐IR, fasting insulin, glucose₁₂₀, and insulin₁₂₀ showed strong correlations with BMI. A total of 1.4 % of nonobese women had IR based on fasting insulin or HOMA‐IR. However, 15.5 % (11/71) of nonobese women had IR as determined by a continuous increase of serum insulin level in OGTT. In comparison, the prevalence of IR among the obese women ranged from 41 to 59 %. AUC_glucose, glucose₆₀, glucose₁₂₀, and insulin₁₂₀ in nonobese women with a continuous insulin increase were higher than those without such a continuous increase.ConclusionsAll examined metabolic parameters were significantly correlated with BMI. As the presence of a continuous increase of insulin level reflects to some degree poorer glucose tolerance, delayed insulin secretion, and enhanced insulin response compared with non‐continuous insulin increase, OGTT might not been excluded to determine IR and IGT for nonobese women with PCOS.     

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 therapy in the management of polycystic ovary syndrome: endocrine, metabolic and reproductive effects.

Polycystic ovary syndrome (PCOS) is a convergence of multisystem endocrine derangements. Impairment in insulin metabolism is a prominent feature of the syndrome and appears to play a key pathogenetic role precipitating the cascade of other disorders associated with PCOS. Recent studies report that insulin-sensitizing agents, such as metformin, reduce hyperinsulinemia, reverse the endocrinopathy of PCOS and normalize endocrine, metabolic and reproductive functions, leading to the resumption of menstrual cyclicity and ovulation. In this review, we report the most recent evidence regarding metformin usage in women with PCOS.     

Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome

OBJECTIVE: Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in the infertility of the polycystic ovary syndrome. Numerous studies indicate that insulin-sensitizing drugs can be used to enhance spontaneous ovulation and the induction of ovulation in the syndrome. The aim of this review is to summarize the studies in which insulin-sensitizing drugs were used to increase ovulation rate or improve fertility in women with the PCOS and to translate the information into practical guidelines for the use of these drugs by reproductive endocrinologists. DESIGN: Review and critique of studies in which an insulin-sensitizing drug was used to increase ovulation rate or improve infertility in women with the polycystic ovary syndrome. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate. RESULT(S): Studies have demonstrated that insulin-sensitizing drugs can increase spontaneous ovulation, enhance the induction of ovulation with clomiphene citrate, and increase clinical pregnancy rates. CONCLUSION(S): An algorithmic approach is provided for the use of insulin-sensitizing drugs to treat the anovulation and infertility of women with the polycystic ovary syndrome.     

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     

Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome

OBJECTIVE: To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective study. SETTING: Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. PATIENT(S): Twenty-four insulin-resistant women with PCOS. INTERVENTION(S): Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. MAIN OUTCOME MEASURE(S): Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. RESULT(S): A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. CONCLUSION(S): Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.     

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS

Abstract

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n?=?138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as – rosiglitazone (R), rosiglitazone with spironolactone (R?+?S), and rosiglitazone with metformin (R?+?M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2?h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R?+?S in improving hyperandrogenism whereas R?+?M was most effective in decreasing body weight and plasma insulin levels compared to R and R?+?S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.     

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.