Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy.

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.     

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。     

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.     

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.     

多囊卵巢综合征患者血循环中瘦素水平及其相关因素的临床研究

目的 :探讨多囊卵巢综合征 (PCOS)患者血循环中瘦素水平与其它内分泌、代谢指标之间的关系 ,进一步研究瘦素的作用规律。方法 :PCOS患者 82例 ,行葡萄糖耐量试验 (OGTT)、胰岛素释放试验 ,测定 5个时点的血糖、胰岛素以及C 肽 (C P)浓度 ;测定空腹血瘦素、性激素及促性腺激素浓度 ;同时测定患者的体重指数 (BMI)、腰臀比例(WHR) ,观察胰岛素增敏剂治疗对瘦素的影响。瘦素和胰岛素用放免法测定 ,C 肽和性激素用发光免疫法测定。结果 :肥胖组瘦素水平显著高于消瘦组 (P =0 .0 0 0 1 ) ,瘦素水平与体重指数呈高度正相关 (P =0 .0 0 0 1 ) ;与腰臀比例、空腹、60min、1 2 0min胰岛素浓度呈显著正相关 (P分别为 0 .0 1 96、0 .0 3 0 8、0 .0 0 0 6、0 .0 0 1 4) ;与OGTT各时点的血糖、C 肽浓度以及血糖、胰岛素、C 肽曲线下面积之间无显著相关性 (P >0 .0 5 )。二甲双胍、文迪雅对瘦素水平无显著影响。结论 :PCOS患者的瘦素浓度与体内脂肪含量及分布密切相关。PCOS患者可能同时存在瘦素抵抗和胰岛素抵抗。用改善胰岛素敏感性药物治疗对瘦素水平无显著影响。     

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.     

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 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.     

Metformin treatment of patients with polycystic ovary syndrome undergoing in vitro fertilization improves outcomes and is associated with modulation of the insulin-like growth factors

OBJECTIVE: To determine if metformin therapy improves in vitro fertilization (IVF) outcomes in patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). DESIGN: Retrospective data analysis of selective groups of patients. SETTING: A private IVF unit. PATIENT(S): Forty-six women with clomiphene citrate-resistant PCOS underwent 60 cycles of IVF embryo transfer with intracytoplasmic sperm injection. INTERVENTION(S): In half of the cycles, patients received metformin (1000 to 1500 mg) daily, starting the cycle prior to gonadotropin treatment. MAIN OUTCOME MEASURE(S): Total number of follicles; serum estradiol (E2) on the day of hCG administration and the cycle's E2 maximum; total number of oocytes, mature oocytes, embryos, fertilization, and pregnancy rates; and follicular fluid levels of insulin-like growth factors (IGF-I, IGF-II) and IGF-binding proteins (IGFBP-1, IGFBP-3). RESULT(S): In patients treated with metformin, the total number of follicles on the day of hCG treatment was decreased (23 +/- 1.2 vs. 33 +/- 2.6) with no change in follicles > or = 14 mm in diameter (21 +/- 1.2 vs. 25 +/- 1.7). Metformin treatment did not affect the mean number of oocytes retrieved (22 +/- 1.9 vs. 20.3 +/- 1.5). However, the mean number of mature oocytes (18.4 +/- 1.5 vs. 13 +/- 1.5) and embryos cleaved (12.5 +/- 1.5 vs. 5.9 +/- 0.9) were increased after metformin treatment. Fertilization rates (64% vs. 43%) and clinical pregnancy rates (70% vs.30%) were also increased. Metformin led to modulation of preovulatory of follicular fluid IGF levels with increases of IGF-I (140 +/- 8 vs. 109 +/- 7ng/mL) and decreased of IGFBP-1 (133 +/- 8 vs.153 +/- 9ng/mL). CONCLUSION(S): Metformin use appears to improve IVF outcomes in patients with clomiphene citrate-resistant PCOS.     

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.     

Predictive value of glucose–insulin ratio in PCOS and profile of women who will benefit from metformin therapy: Obese,lean, hyper or normoinsulinemic?

OBJECTIVE: The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. METHOD: In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. RESULT(S): We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). CONCLUSIONS: Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.     

Combined use of metformin and ethinyl estradiol-cyproterone acetate in polycystic ovary syndrome

OBJECTIVE: The aim of our study was to compare the effect of metformin applied independently to the effect of metformin used in combination with oral contraceptive containing ethinyl estradiol (EE) and cyproterone acetate (CA). STUDY DESIGN: This prospective, open clinical study lasted 6 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 in which Diane35 was added to the same treatment only during the first 2 months of the investigation. 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, on the third and sixth month. Free androgen index (FAI) and 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: Much better and faster decrease in the level of testosterone and free androgen index in group with combined use of metformin and Diane35 was established, without deterioration of the anthropometric and biochemical indices and insulin sensitivity. CONCLUSION: The combination of metformin with intermittent application of Diane35 is an appropriate alternative for the pathogenic influence and clinical improvement of the symptoms of androgen excess in cases with PCOS.     

Effects of metformin on serum insulin and anti-mullerian hormone levels and on hyperandrogenism in patients with polycystic ovary syndrome

Objective: To evaluate the relationship between serum anti-mullerian hormone levels (AMH) and insulin resistance (IR) before and after meformin treatment and to compare AMH levels of polycystic ovary syndrome (PCOS) women in the early follicular phase. Methods: Twenty PCOS women with IR, taking metformin 1500?mg/day for 8 weeks, and 16 non-PCOS controls were enrolled in this longitudinal study. Serum levels of AMH, insulin, glucose, testosterone, and quantitative insulin check index (QUICKI), were assessed before and after treatment in PCOS group. Results: AMH levels were higher in untreated PCOS (p < 0.0001), as were luteinizing hormone (LH) (p = 0.0004), testosterone (p = 0.0017) as well as 17-hydroxyprogesterone (p = 0.03). PCOS women show positive correlation between AMH and testosterone (R = 0.83; p < 0.0001) only prior to treatment. Metformin treatment, lead to a significant decrease in serum insulin (p = 0.0132) and testosterone (p = 0.0017) levels. However, no alteration in AMH levels was observed after treatment. Conclusion: Despite the improvement of metabolic parameters and the reduction of androgen levels, AMH levels did not change after metformin treatment. Maybe, the dose, and possibly the time of use, of metformin are factors associated with the reduction of AMH levels.     

Effects of metformin and ethinyl estradiol-cyproterone acetate on clinical,endocrine and metabolic factors in women with polycystic ovary syndrome

Background. Polycystic ovary syndrome (PCOS) is a major endocrine abnormality that affects women of reproductive age. Oral contraceptive pills are usually the first choice of treatment for PCOS when fertility is not desired. Metformin, an insulin-sensitizing drug, has been shown to improve such metabolic abnormality.

Aim. To compare the effects of a contraceptive pill in combination with metformin on the clinical, endocrine and metabolic parameters in obese and non-obese patients with PCOS.

Methods. Sixty PCOS patients (25 obese, 35 non-obese) were enrolled in this prospective clinical study. PCOS was defined according to the Rotterdam criteria. Patients were randomized to oral treatment with Diane35® (35 μg ethinyl estradiol plus 2 mg cyproterone acetate), metformin or a combination of Diane35/metformin for 3 months. Body mass index (BMI), waist-to-hip ratio (WHR), Ferriman–Gallwey (FG) score, leuteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, fasting insulin and glucose/insulin ratio were measured at baseline and at the end of treatment.

Results. Diane35 resulted in a higher reduction of FG score in both obese and non-obese PCOS patients compared with metformin. Menstrual regularity was restored in all PCOS patients treated with Diane35 compared with only 28% of those receiving metformin. Metformin significantly decreased BMI and WHR in obese patients (p < 0.05). Testosterone levels decreased in all three groups. LH levels and LH/FSH ratio decreased with Diane35 and Diane35/metformin in both obese and non-obese patients. Metformin significantly decreased fasting insulin concentrations (p < 0.05 and p < 0.01) and increased the insulin sensitivity (p < 0.05) in both obese and non-obese PCOS patients, while no significant changes were observed in the Diane35 group. In addition, insulin levels also decreased (p < 0.05) in the Diane35/metformin group.

Conclusions. Our data show that a combination of metformin and contraceptive pill may be more effective in suppressing the hyperandrogenemia of obese and non-obese PCOS patients than metformin alone and may reduce insulin levels more than contraceptive pill alone. Hence, combined treatment may become a more effective therapeutic option for PCOS.     

二甲双胍与复方醋酸环丙孕酮联合应用对多囊卵巢综合征患者内分泌及代谢的影响

目的　观察二甲双胍与复方醋酸环丙孕酮 (复方环丙孕酮 )联合应用 ,对多囊卵巢综合征 (PCOS)患者内分泌及代谢的影响。方法　对 4 5例患者进行前瞻性研究 ,为观察组 ;2 0例非PCOS不孕妇女为对照组。测定体重指数 (BMI)、腰臀围比值 (WHR)、多毛评分 (F G评分 )及生殖内分泌激素、糖、脂代谢指标等。观察组根据随机应用不同药物又分为复方环丙孕酮组、二甲双胍组及二甲双胍与复方环丙孕酮联合用药组 (联合用药组 ) ,每组各 15例。经 12周治疗后 ,比较上述各项指标的变化。结果　观察组治疗前BMI、WHR、F G评分、黄体生成激素 (LH)、睾酮 (T)、空腹胰岛素 (FI)、胰岛素抵抗 (IR)及甘油三酯等均较对照组增高 ;高密度脂蛋白胆固醇 (HDL C)较对照组降低 (P <0 0 1)。观察组 3组治疗前各项指标差异均无显著性 (P >0 0 5 )。治疗 12周后 ,联合用药组及二甲双胍组LH分别从 (13 9± 5 9)IU/L降低为 (5 8± 2 2 )IU/L ,从 (13 8± 7 6 )IU/L降低为 (11 8±6 5 )IU/L ;T分别从 (2 1± 0 8)nmol/L降低为 (1 2± 0 4 )nmol/L ,从 (2 2± 1 1)nmol/L降低为(1 8± 0 8)nmol/L ;游离睾酮 (FT)分别从 (2 8± 2 3)nmol/L降低为 (0 8± 0 5 )nmol/L ,从 (2 5±1 9)nmol/L降低为 (1     

Metformin and Polycystic Ovary Syndrome: A Literature Review

Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects women of reproductive age. Anovulation, menstrual irregularities, hirsutism, and infertility are common clinical presentations. Long-term health concerns such as type II diabetes mellitus and, possibly, cardiovascular disease, have been linked to PCOS. Metformin, an oral hypoglycemic agent, has been recently advocated as treatment for some women with PCOS due to the association of PCOS with hyperinsulinemia. Metformin is utilized as sole therapy for ovulation induction as well as in combination with traditional ovulation-induction therapies. This review identified 23 prospective studies addressing the effects of metformin on PCOS. Because of the heterogeneity of the published reports, only a qualitative assessment of the data was possible. Review of this literature confirms a beneficial role of metformin in reducing insulin resistance in some women with PCOS. Other favourable biochemical effects include reduced free testosterone levels and increased sex hormone-binding globulin (SHBG). Metformin may improve menstrual regularity, leading to spontaneous ovulation, and improve ovarian response to conventional ovulation-induction therapies. There is, however, little evidence supporting the use of metformin to facilitate weight reduction, or improve serum lipids or hirsutism. Further evaluation is required to define the long-term effectiveness of metformin, who will benefit from metformin treatment, and the optimal duration of metformin therapy.     

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.     

The effect of intrauterine and oral levonorgestrel administration on serum concentrations of sex hormone-binding globulin, insulin and insulin-like growth factor binding protein-1.

BACKGROUND: The concentrations of sex hormone-binding globulin (SHBG) have been shown to decrease during the use of levonorgestrel (LNG)-containing contraception. This decrease has been thought to be due to the androgenic action of LNG. In endogenously hyperandrogenic women, particularly in those with increased body weight, serum SHBG correlates with circulating insulin-like growth factor binding protein-1 (IGFBP-1) concentration, and both are inversely related to insulin. LNG-containing combined contraceptives have also been reported to increase the pancreatic insulin secretion. OBJECTIVE: To examine whether serum insulin and IGFBP-1 levels are related to SHBG during the use of intrauterine or oral levonorgestrel contraception. METHODS: Thirty-one fertile women were divided into three study groups: A copper-releasing intrauterine device (IUD) was inserted in control group (n= 10), and the LNG-releasing intrauterine contraceptive system (LNG-IUS) in group II (n= 10), and 30 mirog LNG-containing contraceptive minipills were given in group III (n=11). Twenty-nine women completed the study and one woman was excluded because of a high body mass index. Fasting concentrations of blood glucose, insulin, SHBG, IGFBP-1, testosterone and LNG before and after three-months-use of contraception were measured. RESULTS: SHBG concentrations decreased slightly during oral LNG contraception, but not during the use of the LNG-IUS. No change was found in blood glucose, serum insulin, serum IGFBP-1 and serum total testosterone concentrations in either group. In our study group, including women with normal body weight, no correlation was detected between insulin and SHBG concentrations before or after LNG contraception, whereas an inverse correlation was found between insulin and IGFBP-1 levels at the baseline as well as after LNG-IUS use (R2= 0.578; p=0.001). Multiple regression analysis showed no significant association between the levels of SHBG and IGFBP-1 as dependent factors, and glucose, insulin, LNG, age, waist-hip ratio and body mass index as dependent factors. CONCLUSIONS: Our data imply that the effect of levonorgestrel on variables associated with endogenous hyperandrogenism remains borderline in women with normal body mass index.     

高胰岛素血症在多囊卵巢综合征发病中的作用及抗胰岛素的治疗

目的探讨高胰岛素（ＩＮＳ）血症在多囊卵巢综合征（ＰＣＯＳ）发病中的作用及二甲双胍对ＰＣＯＳ的治疗效果。方法将２３例ＰＣＯＳ病人分为肥胖组（１２例）和非肥胖组（１１例）,于服二甲双胍前及服二甲双胍８～１２周后,应用放射免疫法测定基础状态下雄激素、黄体生成素（ＬＨ）、性激素结合球蛋白及促性腺激素释放激素激动剂（ＧｎＲＨａ）刺激后,血１７α羟孕酮（１７ＯＨＰ）和ＬＨ的水平、口服糖耐量试验（ＯＧＴＴ）中血ＩＮＳ水平。结果用药后肥胖组空腹血ＩＮＳ水平和非肥胖组ＯＧＴＴ时血ＩＮＳ反应曲线下面积均明显下降;两组基础状态下的血１７ＯＨＰ、雄烯二酮（Ａ）、睾酮（Ｔ）水平均显著下降、性激素结合蛋白水平显著增加;ＬＨ基值及ＧｎＲＨａ刺激后的ＯＨＰ和ＬＨ值均无明显变化。结论高ＩＮＳ血症在ＰＣＯＳ的高雄激素血症起重要作用,二甲双胍可用于ＰＣＯＳ的治疗     

The effect of obesity on ovarian function. I. Serum insulin and insulin dependent protein concentrations in obese patients with polycystic ovary syndrome

OBJECTIVES: The aim of the present study was to estimate the role of insulin in the pathogenesis of polycystic ovary syndrome. DESIGN: The study was carried out in 21 obese women with PCO, 18 obese women without menstrual disturbances and 9 normal-weight healthy women. MATERIALS AND METHODS: In all patients antropomethric parameters: weight, height, % of body fat, waist and hip girths were measured and than BMI and WHR were calculated. Oral glucose tolerance test after 75 g glucose was done after overnight fast. Plasma glucose and insulin were measured in 0 min, 60 min and 120 min of the test. The concentrations of IGF-I, IGFBP-1, SHBG, LH, FSH, testosterone, cortisol, PRL, estradiol, were estimated. RESULTS: There was statistical significant difference between plasma insulin concentrations in obese patients with PCO in comparison to obese women with normal menstrual cycle (p < 0.05) and control group (p < 0.001). The concentrations of IGFBP-1 and SHBG were similar in both groups of obese patients and differ markedly in comparison to the control group. There were significant correlation between plasma insulin and % body fat, BMI and waist girth in all studied groups. CONCLUSIONS: We conclude that in obese women with PCO insulin influence ovarian androgen production and decreases the serum SHBG and IGFBP-1 which could contribute in the augmentation of the symptoms of PCO.