Metformin reduces abortion in pregnant women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are considered to be at increased risk of miscarriage. Since metformin has beneficial effects on the risk factors contributing to first-trimester abortion in PCOS patients, we hypothesized that metformin - owing to its metabolic, endocrine, vascular and anti-inflammatory effects - may reduce the incidence of first-trimester abortion in PCOS women. MATERIALS AND METHODS: A prospective cohort study was set up to determine the beneficial effects of metformin on PCOS patients during pregnancy. Two hundred non-diabetic PCOS patients were evaluated while undergoing assisted reproduction. One hundred and twenty patients became pregnant while taking metformin, and continued taking metformin at a dose of 1000-2000 mg daily throughout pregnancy. Eighty women who discontinued metformin use at the time of conception or during pregnancy comprised the control group. RESULTS: Both groups were similar with respect to all background characteristics (age, body mass index, waist/hip ratio, follicle-stimulating hormone, luteinizing hormone, estradiol and dehydroepiandrosterone sulfate levels). Rates of early pregnancy loss in the metformin group were 11.6% compared with 36.3% in the control group (p < 0.0001; odds ratio = 0.23, 95% confidence interval 0.11-0.42). CONCLUSIONS: Administration of metformin throughout pregnancy to women with PCOS was associated with a marked and significant reduction in the rate of early pregnancy loss.     

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 therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome

OBJECTIVE: To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome (PCOS). DESIGN: Prospective and retrospective study. SETTING: Outpatient clinical research center. PATIENT(S): The prospective study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births; of these, 28 were taking metformin through delivery. The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy. INTERVENTION(S): Metformin, 2.55 g/d, throughout pregnancy in women with PCOS. MAIN OUTCOME MEASURE(S): Development of gestational diabetes in women with PCOS. RESULT(S): Before metformin therapy, after covariance adjustment for age, the two cohorts did not differ in height, weight, basal metabolic index, insulin, insulin resistance, or insulin secretion. Both cohorts had high fasting insulin, were insulin resistant, and had high insulin secretion. Among the 33 women who received metformin, gestational diabetes developed in 1 of 33 (3%) pregnancies versus 8 of 12 (67%) of their previous pregnancies without metformin. Among the 39 women who did not take metformin, gestational diabetes developed in 14 of 60 (23%) pregnancies. When all live births were combined, gestational diabetes occurred in 22 of 72 pregnancies (31%) in women who did not take metformin versus 1 of 33 pregnancies (3%) in those who took metformin. With gestational diabetes as the response variable and age at delivery and treatment group (metformin or no metformin) as explanatory variables, the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 (95% CI: 0.011 to 0.795). With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group (metformin no metformin) as explanatory variables, the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 (95% CI: 0.014 to 0.938). CONCLUSION(S): In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31% to 3%). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic beta-cells by insulin resistance and pregnancy.     

Metformin versus lifestyle changes in treating women with polycystic ovary syndrome

Objective: To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS).Design: Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student’s t-test.Results: Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by ~67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8?±?3.9 and 95.1?±?3.6, at baseline and at 6 months of treatment, respectively; p?<?0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI.Conclusions: Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI.     

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

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

Preptin in women with polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) patients, frequently develop metabolic complications, such as insulin resistance (IR), impaired carbohydrate metabolism, dyslipidemia, obesity. Among the new markers responsible for metabolic disorders, preptin seems to be of great significance.

Material: One hundred and thirty-four women aged 17–45 were enrolled. PCOS was diagnosed in 73 women on the basis of ESHRE-ASRM criteria. Non-PCOS group consisted of 61 women with regular menstruation matched for nutritional status.

Methods: All women underwent anamnesis, physical examination, anthropometric measurements, the abdominal ultrasound examination, and dual energy X-ray absorptiometry (DXA). Serum adropin levels were determined by ELISA. Biochemical and hormonal (testosterone, androstenedione, LH, FSH, estradiol) measurements were also performed. Insulin resistance indices (HOMA, QUICKI, Matsuda) and free androgen index (FAI) were calculated with the test results according to the standard formula. For all comparisons, statistical significance was defined by p?≤?.05.

Results: Serum preptin levels were significantly higher in the PCOS group. No significant correlations between preptin level and metabolic and hormonal markers were observed. The logistic regression analysis demonstrated that serum preptin level was an independent factor differentiating the two groups.

Conclusions: Serum preptin levels were significantly higher in women with PCOS compared with controls. This peptide might be an independent predictor of PCOS in the future.     

Serological markers of autoimmunity in pregnant women with polycystic ovary syndrome: a pilot study

Background.?Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes.

Aim.?To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by auto-antibodies.

Methods.?Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22–28, a 2-h, 75?g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies.

Results.?A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCOS women.

Conclusion.?A highly prevalence of anti-GAD65 was observed in women with GDM which is in agreement with previous studies. Nevertheless, the frequency of these auto-antibodies was very low in NP and PPCOS women.     

Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome

Objective

To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling.

Methods

A total of 110 eligible participants were randomly allocated to diagnostic laparoscopy plus metformin therapy (group 1, n = 55) or laparoscopic ovarian drilling (group 2, n = 55). The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment. The χ² test was used for comparisons of ovulation, pregnancy, and abortion rates.

Results

Groups 1 and 2 showed a significant decline in testosterone, insulin-like growth factor-1 (P < 0.001 vs P < 0.001), and luteinizing hormone (P < 0.05 vs P < 0.001), while the glucose to insulin ratio was significantly increased (P < 0.001 vs P < 0.05) compared with baseline. Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1: 76.4% [42/55] vs 58.2% [32/55], P < 0.04; 50.8% [131/258] vs 33.5% [94/281], P < 0.001; and 38.2% [21/55] vs 20.0% [11/55], P < 0.03, respectively. The difference in the early abortion rate between the groups was not statistically significant.

Conclusion

Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.     

Lower serum apelin levels in women with polycystic ovary syndrome

We tested differences in serum apelin levels between women with polycystic ovary syndrome (PCOS) and those with a healthy regular menstrual cycle, finding that apelin levels were higher in normal women and that apelin was positively correlated with apolipoprotein A levels.     

盐酸吡咯列酮治疗多囊卵巢综合征临床疗效分析

目的探讨盐酸吡咯列酮对多囊卵巢综合征（PCOS）患者血清睾酮、血脂、空腹胰岛素、血糖的影响，为其临床应用提供依据。方法应用自身对照研究，对30例PCOS患者给予盐酸毗咯列酮每日30mg口服，3个月。进行服药前后的血清睾酮、血脂、空腹胰岛素、血糖及服糖后2h胰岛素和血糖的测定，同时于服药后记录月经周期、体重变化，服药后不适感及B超监测排卵。结果服药前后体重无明显变化（P〉0．05）。服药后空腹胰岛素、服糖后2h胰岛素和血糖、HOMA指数均有下降（P〈0.05）。服药后血清睾酮明显下降，特别是肥胖组下降明显（P〈0.05），而非肥胖组无变化（P〉0.05）。服药后高密度脂蛋白（HDL）升高，甘油三脂（TG）降低（P〈0.05）。23例无排卵患者服药后观察69个周期，21个周期有排卵，排卵率为30．43％。26例月经异常者中20例得到改善，改善率为76．92％。不良反应中，乳房胀痛1例，胃痛1例，疲劳感1例，其余患者无不适主诉，未发现肝、肾功能异常。结论吡咯列酮可以改善PCOS患者胰岛素抵抗，降低血清睾酮水平，调节脂代谢、诱发排卵，短期应用未出现严重的不良反应。     

A pilot trial of metformin for insulin resistance and mood disturbances in adolescent and adult women with polycystic ovary syndrome

We examine the effects of metformin on insulin resistance (IR) and mood including in adolescent and adult women with polycystic ovary syndrome (PCOS). This trial was conducted in 19 adolescents (age ≤18 years) and 25 adult (age >18 years) women with PCOS. Anthropometric and measurements including, serum glucose, endocrine panel, and lipid profile were performed at baseline. IR was measured by Homeostasis Model Assessment IR (HOMA-IR). Anxiety and depression were measured by Beck’s Anxiety (BAI) and Depression Inventories (BDI-II). All tests were repeated after a 90-day treatment with metformin (1,500?mg/day). The severity of depression and anxiety decreased after 90-day treatment with metformin in women diagnosed with PCOS. The BAI scores were higher in adolescent group while BDI-II scores were higher in the adult group (p?=?.016). After 90-day metformin treatment, both BDI-II and BAI scores were decreased by 3.3 and 3.4, respectively (p?<?.001). Indicators of IR and obesity were improved with this therapy. Although the adolescents weighed lower than the adults, baseline HOMA-IR 5.5?±?1.7 was higher in this group than 4.4?±?1.2 in the adult women (p?=.022). The findings suggest that metformin decrease IR and improve mood both in adolescent and adult women with PCOS.     

Incidence of polycystic ovaries and polycystic ovary syndrome amongst women in Melbourne, Australia

BACKGROUND: The incidence of polycystic ovaries (PCO) in the Australian population is unknown. AIMS: To determine the incidence of PCO in a random population of Melbourne women. METHODS: A retrospective survey of the transvaginal ultrasound of female partners of sterile males was undertaken. RESULTS: Twenty-three percent of subjects had polycystic ovaries on ultrasound criteria, 17% bilateral and 6% unilateral. CONCLUSIONS: The incidence of PCO in Australian women is similar to that of other Caucasian populations.     

Serum visfatin in Asian women with polycystic ovary syndrome

Objective.?To determine serum visfatin levels in Asian polycystic ovary syndrome (PCOS) women and its correlations with various parameters.

Study design.?Case–control study.

Setting.?University hospital.

Subjects.?Eighty women were enrolled in this study. Of these, 40 women were PCOS and 40 age-matched subjects with regular menstrual cycles were controls.

Intervention.?Seventy-five gram oral glucose tolerance tests were performed in all women. Fasting venous blood samples for serum visfatin, insulin and androgen levels were obtained both from the PCOS and the control women.

Main outcome measures.?Serum concentrations of visfatin, fasting insulin (FI), fasting glucose, 2-h post-load glucose (2hPG), homeostasis model assessment insulin resistance, homeostasis model assessment beta cell function, total testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate were measured in both groups.

Results.?Women with PCOS had significantly higher serum visfatin levels than the healthy controls [100.39 ± 41.90 vs. 45.09 ± 28.24 mg/ml, p < 0.01]. PCOS women also had significantly higher concentrations of all androgens (p < 0.01). Insulin resistance seemed to be greater in the PCOS than the control groups, but did not reach a statistically significant level. In the PCOS group, serum visfatin levels were positively correlated with 2hPG, and systolic blood pressure and diastolic blood pressure. Serum visfatin levels were negatively associated with FI (r = ?0.80, p = 0.03) and positively associated with systolic and diastolic blood pressure (r = 0.77, p = 0.04, r = 0.79, p = 0.03, respectively) in the sub-group of PCOS women with abnormal glucose tolerance (AGT).

Conclusions.?Asian PCOS women had significantly higher serum visfatin levels than age-matched healthy controls. Their levels were significantly correlated with 2hPG and blood pressure in PCOS women, and with FI and blood pressure in PCOS women with AGT.     

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.     

Serum visfatin levels in women with polycystic ovary syndrome

The aim of this study is to determine the serum levels of visfatin in patients with polycystic ovary syndrome (PCOS) and to understand its correlations with other metabolic and hormonal parameters. Thirty-seven patients with PCOS and 30 women without concomitant disease were included in this study. Serum visfatin levels were similar in patients with PCOS and control group. Visfatin levels were higher in normal weight PCOS when compared with obese PCOS, but it did not reach statistical significance. Visfatin levels correlated negatively with fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL) and lipoprotein-a levels in PCOS patients. CRP levels increased both in obese PCOS and in obese controls. Plasma visfatin levels had no correlation with homeostasis model assessment-insulin resistance and fasting insulin levels, but the negative correlation between plasma visfatin levels and lipoprotein-a, fasting plasma glucose, TC and LDL levels may indicate a role for visfatin in cardiovascular disease independent of insulin resistance.     

Insulin-lowering treatment reduces aromatase activity in response to follicle-stimulating hormone in women with polycystic ovary syndrome

OBJECTIVE: To investigate the effects of reduction of insulin resistance and hyperinsulinemia associated with the polycystic ovary syndrome (PCOS) on FSH-stimulated ovarian aromatase activity. DESIGN: Prospective study. SETTING: Academic health center, Siena, Italy. PATIENT(S): Twenty women 18 to 26 years of age in whom PCOS was diagnosed on the basis of oligomenorrhea or amenorrhea and hyperandrogenemia. INTERVENTION(S): Recombinant FSH was administered. The next day, therapy with metformin (500 mg t.i.d.) was begun. After 35 to 40 days of treatment, the pretreatment protocol was repeated. MAIN OUTCOME MEASURE(S): Plasma levels of estradiol (E(2)), androstenedione (A), and testosterone (T). The ratios of basal levels and areas under the curve (AUCs) of products and substrates were compared before and after metformin administration to detect differences in aromatase activity. RESULT(S): Metformin treatment was associated with significant reduction in basal free testosterone plasma levels, insulin plasma levels, and insulin response to oral glucose tolerance testing. Administration of FSH was followed by a significantly lesser E(2) response after metformin therapy than before this therapy. The ratios of AUC(E2) to AUC(A) and to AUC(T), indicative of aromatase activity in response to FSH, were significantly lower after metformin therapy than before. CONCLUSION(S): Metformin therapy in women with PCOS is associated with a reduction in aromatase activity in response to FSH. Insulin affects production of both androgen and estrogen. Insulin therefore plays a central role in regulating the activity of thecal and granulosa cells.