Metformin therapy increases insulin-like growth factor binding protein-1 in hyperinsulinemic women with polycystic ovary syndrome

OBJECTIVES: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance, compensatory hyperinsulinemia, and increased levels of free insulin-like growth factor-I (IGF-I), presumably due to a decline in IGF binding protein 1 (IGFBP-1). This study was designed to evaluate effects of metformin therapy on serum levels of IGFBP-1 and IGF-I. STUDY DESIGN: Twenty-seven obese, hyperandrogenic PCOS women with elevated fasting insulin were treated for 12 weeks with metformin (500 mg p.o., t.i.d.). Serum levels of insulin, testosterone, sex hormone binding globulin (SHBG), IGF-I, and IGFBP-1 were measured before and after treatment. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed at baseline and at the end of therapy. RESULTS: Metformin therapy significantly increased IGFBP-1 concentration by 38% (P = 0.05) but had no demonstrable effect on the total IGF-I levels. Fasting insulin levels declined by 38% (P = 0.0001) while the glucose/insulin ratio increased by 72% (P = 0.0001) and quantitative insulin sensitivity check index (QUICKI) increased by 8% (P = 0.0001). Metformin treatment also significantly decreased testosterone (by 37%, P = 0.0001) and increased SHBG concentration (by 16%, P = 0.04). Multiple linear regression analysis revealed that baseline IGFBP-1 levels correlated inversely and independently with two baseline parameters: WHR (P = 0.003) and free testosterone index (P = 0.04). CONCLUSIONS: The present study shows that metformin therapy not only restores normal levels of insulin and testosterone, but also decreases the pool of free-bioactive IGF-I by increasing the levels of circulating IGFBP-1. We provide further arguments in favor of metformin therapy in hyperinsulinemic women with PCOS.     

Effects of metformin on clinical and biochemical parameters in polycystic ovary syndrome

OBJECTIVE: To assess the effects of 6 months of metformin therapy on clinical and biochemical parameters in polycystic ovary syndrome (PCOS) and to evaluate those parameters in responders and nonresponders to identify the subjects who respond to an insulin sensitizer in PCOS. STUDY DESIGN: Sixty-six diagnosed PCOS patients were recruited. Baseline characteristics (menstrual history, hirsutism scoring, acne grading, body mass index [BMI], serum luteinizing hormone and follicule-stimulating hormone [LH/FSH] ratio, testosterone,fasting insulin and glucose/insulin index) were assessed initially and 6 months after metformin therapy. Three groups were constructed on the basis of menstrual symptoms: oligomenorrhea (group I), amenorrhea (group II) and hypomenorrhea (group III). Responders were those who had improvements in menstrual pattern or conceived. Response was compared in 3 groups, and biochemical parameters were compared in responders and nonresponders. RESULTS: There were 44 (66.6%) oligomenorrheic, 17 (25.7%) amenorrheic and 5 (7.5%) hypomenorrheic cases and 31 (46.5%) infertile women. In total, 85.7% responded to treatment; the rest (14.3%) were nonresponders. Among responders, 62.29% achieved regular periods, 22.95% experienced improvements in their menstrual abnormalities, and 13% conceived. Overall, a significant reduction occurred in BMI (P =.04), mean testosterone (P = .03) and mean fasting insulin levels (P = .01), but no significant improvement was observed in hirsutism, acne, LH/FSH ratio or glucose/insulin index. A total of 9.75%, 18.75% and 30% did not respond in the oligomenorrheic, amenorrheic and hypomenorrheic groups, respectively (P = .04). Testosterone and insulin were reduced significantly in responders (P = .05 and .01, respectively) but not in nonresponders (P = .26 and .73). An initial high LH/FSH ratio and lower testosterone levels were associated with a better response. CONCLUSION: Six months of metformin therapy improved menstrual cyclicity and fertility in women with PCOS. It resulted in a decline in testosterone and insulin levels. Oligomenorrheic patients with an increased LH/FSH ratio and lower testosterone levels responded better.     

Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome

Objective: To evaluate the effects of 12 weeks of metformin therapy on hormonal and clinical indices in polycystic ovary syndrome (PCOS).

Design: Prospective study.

Setting: University hospital.

Patient(s): Thirty-nine women with PCOS and fasting hyperinsulinemia.

Intervention(s): Twelve weeks of therapy with oral metformin (500 mg three times per day).

Main Outcome Measure(s): Levels of insulin, T, DHEAS, insulin-like growth factor-I (IGF-I), gonadotropins, and sex hormone-binding globulin (SHBG); and clinical symptoms including acne, hirsutism, and length of the menstrual cycle were assessed before and after treatment with metformin.

Result(s): Metformin therapy resulted in a significant decrease in fasting insulin and total T and an increase in SHBG, leading to a decrease in the free T index. In addition, there was a significant decline in mean body mass index, waist-hip ratio, hirsutism, and acne, as well as an improvement in the menstrual cycle. No changes in LH and LH-FSH ratio were observed. Multiple regression analysis demonstrated that the greatest decline of T and free T index in response to metformin was observed among patients with the most pronounced hyperandrogenemia. Subjects with elevated DHEAS differed from those with normal DHEAS in their responses to metformin treatment. Women with high DHEAS exhibited less improvement of menstrual cycle regularity, no change in hirsutism, and an increase in levels of IGF-I after treatment.

Conclusion(s): Metformin treatment of women with PCOS results in a decline of insulin as well as total and bioavailable T, leading to significant improvement of clinical manifestations of hyperandrogenism. Responses to metformin are related to the severity of hyperandrogenemia and to adrenal function.     

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.     

Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases in women. This syndrome is characterized by hyperandrogenism, chronic anovulation, infertility and obesity. The association between PCOS-related hyperandrogenemia and insulin resistance is well documented in the literature. Insulin resistance and the resulting raised plasma levels of insulin are reported to be responsible for the high androgen concentration observed in patients with PCOS. In this prospective study, blood samples for levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, prolactin and fasting blood sugar (FBS) before starting metformin administration were obtained randomly from 40 women who were apparently obese, had PCOS and had been referred to a university hospital. Metformin was then given at a dose of 500 mg three times a day for 8 weeks, after which time the pretreatment study was repeated. Clinical symptoms of PCOS, including acne and hirsutism score and body mass index (BMI), were assessed before and after the treatment cycle. Metformin therapy resulted in a significant decrease in total testosterone levels and FBS. There was also a significant decline in BMI, length of the menstrual cycle, acne and hirsutism score. There were no significant changes in the levels of DHEAS, prolactin, FSH or LH, or in LH/FSH. The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels. In the latter group there were only significant improvements in the length of the menstrual cycle, BMI and testosterone and DHEAS levels. It is concluded that metformin therapy in subjects with PCOS results in a decrease in fasting blood sugar and testosterone levels, and leads to a significant improvement in the clinical manifestation of hyperandrogenism. These responses also related to the level of adrenal function.     

Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome.

Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice. We evaluated the effects of 6 months' administration of metformin on clinical and endocrine indices in PCOS patients. Forty-two hyperinsulinemic women with PCOS were continuously treated with metformin for 6 months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR)) were studied before and after metformin treatment. All women experienced a normalization of menstrual cycle length (reduction rate, 36.9%), a significant decrease in luteinizing hormone, insulin and androgen levels and an increase in SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR. Significant changes were observed in the lipid profile. According to baseline androgen levels, patients were divided into two groups: 20 normoandrogenic and 17 hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman-Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity was independent of BMI. Significant changes in lipid profile were observed in both groups after metformin treatment. These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This leads to an improvement of clinical manifestations of PCOS and, in particular, of hyperandrogenism.     

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。     

Clinical and endocrinological effects of 6 months of metformin treatment in young hyperinsulinemic patients affected by polycystic ovary syndrome

Most patients with polycystic ovary syndrome (PCOS) have hyperinsulinemia; thus it has been postulated that insulin-lowering drugs, such as metformin, might be a useful long-term choice. We evaluated the effects of 6 months' administration of metformin on clinical and endocrine indices in PCOS patients. Forty-two hyperinsulinemic women with PCOS were countinuously treated with metformin for 6 months. Gonadotropins, androgens (testosterone and androstenedione), insulin, sex hormone binding globulin (SHBG), lipid profile and clinical indices (menstrual length, body mass index (BMI), Ferriman-Gallwey score and waist/hip ratio (WHR)) were studied before and after metformin treatment. All women experienced a normalization of menstrual cycle length (reduction rate, 36.9%), a significant decrease in luteinizing hormone, insulin and androgen levels and an increase in SHBG plasma concentrations, with a concomitant decrease in cycle length and WHR. Significant changes were observed in the lipid profile. According to baseline androgen levels, patients were divided into two groups: 20 normoandrogenic and 17 hyperandrogenic women. The greatest decline of androgens, BMI and Ferriman-Gallwey score was observed in hyperandrogenic patients. Lowering of androgenicity was independent of BMI. Significant changes in lipid profile were observed in both groups after metformin treatment. These results suggest that metformin is effective in decreasing hyperandrogenism, mainly by reducing insulin levels. This leads to an improvement of clinical manifestations of PCOS and, in particular, of hyperandrogenism.     

二甲双胍治疗多囊卵巢综合征有效性相关因素的探讨

目的:探讨二甲双胍在治疗多囊卵巢综合征(PCOS)中的作用,总结其治疗PCOS有效性的可能影响因素,为PCOS合理的临床治疗方案提供理论依据。方法:40例PCOS患者,应用二甲双胍500 mg/次,3次/d,连续3个月。比较治疗前后临床症状、内分泌和生化指标的改变。并根据临床症状是否改善分为有反应组和无反应组,比较两组治疗前后上述指标的不同。结果:38例完成了二甲双胍的治疗,有反应者24例(63.16%),无反应者14例(36.84%)。总体上治疗后,体重指数(BMI)、腰臀比(WHR)、LH、LH/FSH、T、空腹胰岛素(FINS)、胰岛素曲线下面积(IAUC),胰岛素敏感指数(ISI)有明显的提高,差异均有显著性或非常显著性(P<0.05,<0.01)。LH、LH/FSH比值、TF、INSI、AUCI、SI的明显改变只发生在有反应组。两组治疗前比较,有反应组月经失调的时间较短、程度较轻、体重指数较小I、SI较高、T水平明显低于无反应组(P<0.05)。结论:二甲双胍可改善临床症状,降低LH/FSH比值、LH、T水平,提高胰岛素的敏感性。月经失调时间越短、月经失调中月经稀发者、体重指数较小、T水平较低I、SI较高者对二甲双胍的反应性较好。     

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective

To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters.

Study design

We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS.

Results

From all patients, 30 (56.6%) were responders and 23 (43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015).

Conclusion

In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects.     

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.     

Management of polycystic ovarian syndrome with Diane-35 or Diane-35 plus metformin

In this study, we assessed the efficacy and safe usage of the oral contraceptive, Diane-35, in the treatment of polycystic ovary syndrome (PCOS) when combined with the drug metformin. Eighty-two patients with PCOS were randomly divided into two equal groups: Diane-35 treatment group and Diane-35 plus metformin group. Three treatment cycles were administered. Patients’ biomedical data such as height, weight, waist circumference, hip circumference, body fat percentage, acne score, hirsutism score and serum hormone levels were selected, which were tested between the second and the fifth day of the menstrual cycle and follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), blood glucose, blood lipids and insulin levels(IR) were analyzed. Significant reduction in body mass index (BMI), acne score, LH and T levels were observed in both groups after three months of treatment; on the other hand, high-density lipoprotein cholesterol (HDL) concentration elevated (p?p?相似文献   

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.     

Lack of insulin-like growth factor binding protein-3 variation after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization.

OBJECTIVE: To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Naples. PATIENT(S): Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF. INTERVENTION(S): The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay. RESULT(S): The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation. CONCLUSION(S): The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.     

Metformin administration is more effective when non-obese patients with polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that is frequently observed to be related to increased insulin resistance independent of body weight. The use of insulin-sensitizer compounds, such as metformin, permits great improvement of such metabolic abnormality, restoring ovarian function and gonadal steroid synthesis and reducing insulin resistance. AIM: On this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients before and after 6 months of metformin administration (500 mg orally twice daily) to better understand upon which basis of clinical and endocrine parameters metformin administration might be chosen as a putative therapeutic tool. METHOD: A group of non-obese PCOS patients (n = 42) was enrolled after informed consent. They underwent an oral glucose tolerance test for insulin, glucose and C-peptide levels and provided blood samples for determination of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol, androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone levels on two occasions: before and on day 7 of the first menstrual cycle occurring after the 5th month of treatment. RESULTS: Plasma LH, estradiol, insulin and C-peptide were decreased significantly by metformin treatment in the entire group of PCOS patients. When subdividing PCOS patients according to insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate of positive endocrine changes was observed in hyperinsulinemic patients and the highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual cyclicity was recovered in all patients under treatment. CONCLUSIONS: Our data show that metformin modulates ovarian function and greatly affects LH secretion through reduction of the hyperandrogenic condition. The highest rate of endocrine changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS patients. Our study demonstrates that metformin administration is more appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.     

Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome.

A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20 +/- 5.02 years and treated with metformin (1500 mg/day)for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33 +/- 0.03 to 0.35 +/- 0.04 (p < 0.005), and serum total cholesterol and low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.     

Polycystic ovary syndrome: evolution of a concept.

Despite improved diagnostic facilities and advanced in vitro studies, the primary causes of the polycystic ovary syndrome (PCOS) have not been resolved. In addition to certain enzyme deficiencies causing a PCOS-like state, current evidence indicates altered functions of 5 alpha-reductase and cytochrome P450c17 alpha in PCOS patients as a group. However, it is not obvious if these are primary or secondary to the abnormal hormonal milieu. The relation of insulin-like growth factors (IGFs) to PCOS is of particular interest in view of the occurrence of IGF-II mRNA in the granulosa cells and the ability of IGF-I to regulate the granulosa cell and thecal-interstitial cell functions. In obese PCOS patients, the levels of sex hormone binding globulin and IGF-binding protein-1 are subnormal in serum, and fasting increases them. Fasting also suppresses high insulin and IGF-I concentrations in the same women. Growth hormone, regulated by insulin and probably by IGF-I, appears to be decreased in PCOS patients. Follicular growth, characteristically arrested in PCOS, is regulated by growth hormone to some extent, and growth hormone treatment has been found to improve the ovarian response to gonadotropins in some but not all anovulatory patients. In addition to the administration of growth hormone itself, therapeutic measures modulating the growth hormone-ovarian axis are being studied. High serum luteinizing hormone levels are typical of PCOS. These are often associated with infertility and early pregnancy loss. Lowering of the luteinizing hormone levels by a gonadotropin-releasing hormone analogue in combination with gonadotropins improves the outcome of pregnancies as compared with those achieved by clomiphene citrate. The use of the former regimen in PCOS patients may result in ovarian hyperstimulation. Ovarian electrocautery has proved to be effective in restoring cyclicity of ovarian function with a concomitant fall in luteinizing hormone and androgen levels. Interestingly, an increase in serum insulin secretion has been noted. It remains to be elucidated if this therapy, followed by decreased luteinizing hormone, is effective in reducing the elevated risk of miscarriages in women with PCOS.     

罗格列酮对多囊卵巢综合征胰岛素抵抗及高雄激素血症的治疗研究

目的　探讨胰岛素增敏剂罗格列酮对多囊卵巢综合征 (PCOS)的胰岛素抵抗及高雄激素血症的治疗效果。方法　对 30例PCOS患者给予每天早餐前口服 4mg罗格列酮 ,共 1 2周 ,比较治疗前后体重指数、胰岛素、血糖和血脂、瘦素和神经肽Y以及生殖激素水平与排卵率的变化。结果治疗 1 2周后 ,基础胰岛素水平从 (1 8± 8)mIU/L降至 (1 2± 7)mIU/L(P <0 0 1 ) ,胰岛素抵抗指数从4 3± 1 2降至 2 6± 0 7(P <0 0 1 )。黄体生成素从 (1 5 4± 4 4)U/L降至 (7 9± 2 1 )U/L ,游离睾酮从(1 2 5± 1 9)pmol/L降至 (8 9± 1 4)pmol/L ,雄烯二酮从 (9 8± 1 7)nmol/L降至 (7 4± 1 2 )nmol/L ,差异均有极显著性 (P均 <0 0 1 ) ;硫酸脱氢表雄酮从 (8 7± 3 5) μmol/L降至 (6 9± 2 1 ) μmol/L(P<0 0 5) ;性激素结合球蛋白从 (39± 3)nmol/L升至 (58± 5)nmol/L(P <0 0 1 )。血浆瘦素水平从 (1 8±4) μg/L降至 (1 3± 3) μg/L(P <0 0 1 )。 30例月经稀发的患者 ,2 5例恢复排卵 ,排卵率 50 %。 结论　罗格列酮可降低PCOS患者血浆瘦素水平 ,改善胰岛素敏感性 ,进而改善高雄激素血症等内分泌紊乱 ,恢复有排卵月经     

Effect of metformin on the clinical and metabolic assessment of women with polycystic ovary syndrome

A longitudinal prospective study was conducted in 21 women with polycistic ovary syndrome (PCOS), aged 27.20?±?5.02 years and treated with metformin (1500?mg/day) for 8 weeks. The patients were assessed for spontaneous menstruation, weight, body mass index (BMI), waist circumference, waist/hip ratio (WHR), glucose and insulin concentrations under fasting conditions and after a 75-g glucose tolerance test, lipid profile, testosterone, androstenedione, dehydroepiandrosterone sulfate, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF)-I. Spontaneous menstruation was observed in 81% of the women treated with metformin, with no changes in weight or BMI. Waist measurement and the WHR were reduced. The quantitative insulin sensitivity check index (QUICKI) improved from 0.33?±?0.03 to 0.35?±?0.04 (p?<?0.005), and serum total cholesterol and low-density lipoprotein-cholesterol were reduced, while high-density lipoprotein-cholesterol was increased. Serum testosterone concentrations were also reduced. There were no differences in serum triglycerides, SHBG or IGF-I. The occurrence of spontaneous menstruation and changes in the pattern of body fat distribution, the reduction in serum testosterone concentrations, the improvement in lipid profile and the reduction of insulinemia with the use of metformin permit us to conclude that treatment with this drug is of benefit to women with PCOS.     

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.