The Effect of Metformin on Polycystic Ovary Syndrome in Overweight Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
ABSTRACT: Objective:Metformin is an important component of PCOS treatment. At present, the effect of metformin in overweight women with PCOS has not been evaluated. Therefore, we conducted a systematic review to assess the effects of metformin in overweight women with PCOS and to analyze the effects of metformin in overweight women with PCOS. Methods:We searched the PubMed, Cochrane Library, Embase, CNKI, VIP, and Wanfang databases for studies published before March 2020. Randomized controlled trials were identified to study the effects of metformin in overweight women with PCOS. Data from studies including body mass index (BMI), waist circumference (WC), follicle-stimulating hormone (FSH), homeostasis model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), fasting blood glucose (FBG), fasting insulin, testosterone, and androstenedione were pooled. Qualified trials were selected, and methodological quality was strictly assessed. Two reviewers chose the studies independently of each other. Results:Twelve trials were included. The intervention group and the control group had significant differences in the changes in body mass index (BMI) (WMD?=?-1.25, 95% CI (-1.60, -0.91), p < 0.00001) and waist circumference (WC) (WMD?=?-1.41, 95% CI (-2.46, -0.37), p=0.008) after metformin. The comprehensive results show that, in all studies, overweight women with polycystic ovary syndrome treated with metformin had significantly improved endocrine and metabolic indicators, including testosterone, follicle-stimulating hormone, luteinizing hormone, and low-density lipoprotein cholesterol. However, metformin did not regulate the secretion indexes of fasting insulin, homeostasis model assessment of insulin resistance, sex hormone-binding globulin, high-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting blood glucose, and androstenedione. Conclusions:Compared with control interventions, metformin appears to be an effective intervention for overweight women with PCOS.
Project description:OBJECTIVE:To evaluate the efficacy of insulin sensitizers on menstrual frequency, sex hormone, and metabolic parameters in overweight women with polycystic ovary syndrome (PCOS). METHODS:We searched multiple databases from inception to September 2019 for randomized controlled trials. Network meta-analysis was conducted using multivariate random effects method. RESULTS:Fourteen trials reporting on 619 women were included. Compared with metformin, metformin?+?thiazolidinediones (TZDs) was more superior in menstrual recovery (weighted mean difference [WMD] 3.68; 95% credibility interval [CrI], 1.65 to 8.20), metformin?+? glucagon-like peptide-1 (GLP-1) receptor agonists was more effective in decreasing androstenedione (WMD -2.53; 95% CrI, -3.96 to -1.09), both metformin?+?GLP-1 receptor agonists (WMD 9.22; 95% CrI, 5.46 to 12.98) and metformin?+?TZDs (WMD 4.30; 95% CrI, 0.78 to 7.82) were more effective in increasing sex hormone-binding globulin (SHBG), while TZDs were less effective in decreasing body mass index (BMI) (WMD 1.69; 95% CrI, 0.72 to 2.66). Compared with GLP-1 receptor agonists, metformin?+?GLP-1 receptor agonists was associated with higher SHBG (WMD 7.80; 95% CrI, 4.75 to 10.85), lower free testosterone (WMD -1.77; 95% CrI, -3.25 to -0.29), lower androstenedione (WMD -2.70; 95% CrI, -3.91 to -1.50) and lower fasting blood glucose (WMD -0.41; 95% CrI, -0.73 to -0.08). CONCLUSION:For overweight women with PCOS, both metformin combined with GLP-1 receptor agonists and metformin combined with TZDs appear superior to monotherapy in improving hyperandrogenemia. Metformin combined with TZDs could be particularly effective in promoting the recovery of menstruation. Metformin combined with GLP-1 receptor agonists has the additional advantage of improving fasting glucose when compared with GLP-1 receptor agonists alone. TZDs are inferior to metformin in decreasing BMI.
Project description:Polycystic ovary syndrome (PCOS) is the most common endocrine disease and associated with insulin resistance. CXC Ligand 5 (CXCL5) is a new cytokine which is secreted from white adipose tissue during obesity and by blocking insulin signaling pathway inhibits the activity of insulin and promotes insulin resistance.The aim of this study was to assess serum level of CXCL5 in PCOS women with normal body mass index.In this case-control study, 30 PCOS women with normal body mass index as the case group and 30 non-PCOS women as the controls were enrolled. Serum levels of CXCL5, insulin and other hormones factors related with PCOS were measured by ELISA method, also the biochemical parameters were measured by autoanalyzer.Significant increases in serum insulin concentration, homeostasis model assessments of insulin resistance, luteinizing hormone, luteinizing hormone/follicle-stimulating hormone, fasting blood sugar, testosterone, and prolactin were observed in the case group compared to the controls. were in the serum level of CXCL5, cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol,dehydroepiandrosterone-sulfate, creatinine, and homeostasis model assessment of beta cell function between these two groups.In this study, no significant change was observed in serum concentrations of CXCL5 in PCOS women with normal BMI.
Project description:Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response.The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment.We conducted an open-label, interventional study at an academic medical center.Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study.Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters.Changes in glucose and insulin parameters, androgen levels, anthropometric measurements, and ovulatory menstrual cycles were evaluated.Insulin sensitivity did not change despite weight loss. Glucose effectiveness (P = .002) and the acute insulin response to glucose (P = .002) increased, and basal glucose levels (P = .001) decreased after metformin treatment. T levels also decreased. Women with improved ovulatory function (61%) had lower baseline T levels and lower baseline and stimulated T and androstenedione levels after metformin treatment (all P < .05).Using an IV glucose tolerance test, which distinguishes improvements in glucose effectiveness and insulin sensitivity, metformin does not improve insulin sensitivity in women with PCOS but does improve glucose effectiveness. The improvement in glucose effectiveness may be partially mediated by decreased glucose levels. T levels also decreased with metformin treatment. Ovulation during metformin treatment was associated with lower baseline T levels and greater T and androstenedione decreases during treatment, but not with insulin or LH levels. Thus, the action of metformin in PCOS primarily affects glucose levels and steroidogenesis, which may be mediated by mechanisms that affect both pathways, such as inhibition of mitochondrial complex I.
Project description:OBJECTIVE:Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. METHODS:A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. RESULTS:Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). CONCLUSION:Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.
Project description:BACKGROUND:Metformin has shown its effectiveness in reducing body mass index (BMI) in obese children and adolescents, but relevant evidence for improving insulin resistance in overweight or obese children and adolescents is inconclusive. OBJECTIVES:This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-density lipoprotein cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C). METHODS:Searches were carried out in PubMed, CENTRAL, Web of Science, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), and WanFang from their inception until March 2018. Randomized controlled trials (RCTs) comparing metformin alone with placebo in overweight or obese children and adolescents were included. The Cochrane risk of bias tool was applied to assess the methodological quality of every study and Meta-analysis was carried out with a random effects model or a fixed effects model. Publication bias was evaluated by the Begg and Egger tests. RESULTS:A total of 11 trials with a total of 865 participants met the inclusion criteria. Participants were between 4 and 18 years old. The time span of these studies ranged from 2001 to 2017. The daily dose of metformin was from 1000?mg to 2000?mg and the duration of intervention was 8 weeks to 18 months. Compared with placebo, metformin with lifestyle intervention reduced the level of LDL-C (P?=?008, MD = - 4.29, 95% confidence interval [CI]: -7.45, -1.12). However, there was no obvious differences in improving insulin resistance, fasting glucose, and HDL-C. CONCLUSION:Metformin may improve the level of LDL-C, but it has no significant effect on insulin resistance. The use of metformin may be a new approach to lipid metabolism management in overweight or obese children and adolescents. REGISTRATION NUMBER:CRD42018092059.
Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during reproductive age. It is characterised clinically by oligo-ovulation or anovulation, hyper-androgenism, and the presence of polycystic ovaries. It is associated with an increased prevalence of metabolic syndrome, cardiovascular disease and type 2 diabetes. The onset of PCOS has been associated to several hereditary and environmental factors, but insulin resistance plays a key pathogenetic role. We sought to investigate the effects of a ketogenic diet (KD) on women of childbearing age with a diagnosis of PCOS. METHODS:Fourteen overweight women with diagnosis of PCOS underwent to a ketogenic Mediterranean diet with phyoextracts (KEMEPHY) for 12 week. Changes in body weight, body mass index (BMI), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), insulin, glucose, HOMA-IR, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TGs), total and free testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH); dehydroepiandrosterone sulfate (DHEAs), estradiol, progesterone, sex hormone binding globulin (SHBG) and Ferriman Gallwey score were evaluated. RESULTS:After 12 weeks, anthropometric and body composition measurements revealed a significant reduction of body weight (-?9.43 kg), BMI (-?3.35), FBM (8.29 kg) and VAT. There was a significant, slightly decrease of LBM. A significant decrease in glucose and insulin blood levels were observed, together with a significant improvement of HOMA-IR. A significant decrease of triglycerides, total cholesterol and LDL were observed along with a rise in HDL levels. The LH/FSH ratio, LH total and free testosterone, and DHEAS blood levels were also significantly reduced. Estradiol, progesterone and SHBG increased. The Ferriman Gallwey Score was slightly, although not significantly, reduced. CONCLUSIONS:Our results suggest that a KD may be considered as a valuable non pharmacological treatment for PCOS. Longer treatment periods should be tested to verify the effect of a KD on the dermatological aspects of PCOS. Trial registration Clinicaltrial.gov, NCT04163120, registrered 10 November 2019, retrospectively registered, https://clinicaltrials.gov.
Project description:Objective:Long-term efficacy of metformin in polycystic ovarian syndrome (PCOS) apart from in those with impaired glucose tolerance or diabetes remains unproven. We aimed to evaluate the impact of metformin in overweight-obese patients with PCOS and normal baseline glycemic homeostasis. Methods:A 10-year longitudinal follow-up of a retrospective cohort comprising 159 patients with PCOS defined by Rotterdam criteria, BMI ?25 kg/m2 and normal initial glucose homeostasis (age 28.4 ± 6.4 years, BMI 34.9 ± 6.6 kg/m2) that had been receiving metformin 1000 mg BID. Collection data contained 6085 time-points including anthropometric, hormonal and metabolic parameters. Results:After the first year body mass (BM) decreased for 3.9 ± 6.8 kg (P < 0.001) and remained stable during the following 3 years. Menstrual frequency (MF) increased to 3.0 ± 3.9 bleeds/year (P < 0.001) after first year to over 11 bleeds/year in the following years. The total testosterone and androstenedione decreased to 15.4 ± 47.9% and 11.3 ± 46.4% within first year, with further decrease in total testosterone and androstenedione to 37.8 ± 61.8 and 24.8 ± 40.5% at the fifth year of the follow-up. The total conversion rate to prediabetes and diabetes was extremely low throughout observation period. Less than 25% of patients continued with metformin for more than 5 years with further dropout to only 6% on metformin therapy at the tenth year of follow-up. Conclusions:Long-term metformin treatment of overweight-obese women with PCOS and normal baseline glycemic homeostasis resulted in reduction and stabilization of BM, improvements of MF and androgen profile and low conversion rate to diabetes.
Project description:CONTEXT:Large, longitudinal studies on androgen levels in pregnant women with polycystic ovary syndrome (PCOS) are lacking. While metformin has a mild androgen-lowering effect in non-pregnant women with PCOS, its effects on maternal androgen levels in pregnancy are less well understood. OBJECTIVE:To describe androgen patterns in pregnant women with PCOS and in healthy control women, and to explore the potential effects of metformin on maternal androgen levels in PCOS. DESIGN AND SETTING:A post hoc analysis from a randomized, placebo-controlled, multicenter study carried out at 11 secondary care centers and a longitudinal single-center study on healthy pregnant women in Norway. PARTICIPANTS:A total of 262 women with PCOS and 119 controls. INTERVENTION:The participants with PCOS were randomly assigned to metformin (2 g daily) or placebo, from first trimester to delivery. MAIN OUTCOME MEASURES:Androstenedione (A4), testosterone (T), sex-hormone binding globulin (SHBG), and free testosterone index (FTI) at 4 time points in pregnancy. RESULTS:Women with PCOS versus healthy controls had higher A4, T, and FTI, and lower SHBG at all measured time points in pregnancy. In the overall cohort of women with PCOS, metformin had no effect on A4, T, SHBG, and FTI. In subgroup analyses, metformin reduced A4 (P?=?0.019) in nonobese women. Metformin also reduced A4 (P?=?0.036), T (P?=?0.023), and SHBG (P?=?0.010) levels through pregnancy in mothers with a male fetus. CONCLUSION:Metformin had no effect on maternal androgens in PCOS pregnancies. In subgroup analyses, a modest androgen-lowering effect was observed in nonobese women with PCOS. In PCOS women carrying a male fetus, metformin exhibited an androgen-lowering effect.
Project description:Background Previous studies have suggested that Fetuin-B seems to be a secreted adipokine related to metabolic diseases. However, the results have been inconsistent. Here, our objective is to investigate the changes in circulating Fetuin-B levels in women with polycystic ovary syndrome (PCOS) and analyze the association of Fetuin-B and insulin resistance (IR). Methods The current study is comprised of a cross-sectional study and a series of interventional studies. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp (EHC) were engaged to assess glucose tolerance and insulin sensitivity. Serum Fetuin-B levels were determined by ELISA. Results Serum Fetuin-B and TNF-? levels were markedly increased in women with PCOS compared to healthy women. Circulating Fetuin-B was positively associated with body mass index, waist-to-hip ratio, the percentage of body fat (FAT%), systolic blood pressure, triglyceride, low-density lipoprotein cholesterol, fasting blood glucose, 2?h blood glucose after glucose overload, fasting insulin, 2?h insulin after glucose overload, HOMA-insulin resistance index (HOMA-IR), the area under the curve for insulin (AUCi), AUCg, and TNF-?, while negatively associated with M value and follicular stimulating hormone (FSH). During the EHC, Fetuin-B levels were found to be significantly increased in PCOS women. After a glucose challenge, serum Fetuin-B levels in healthy women were significantly increased. Lipid infusion reduced serum Fetuin-B levels in 30 healthy subjects. After six months of glucagon-like peptide-1 receptor agonist (GLP-1RA) intervention, serum Fetuin-B concentrations in PCOS women markedly decreased following ameliorated IR. Conclusion Our results indicate that Fetuin-B may be a biomarker of IR in individuals with PCOS. This trial is registered with ChiCTR-IIR-16007901.
Project description:To assess effects of vitamin D and Calcium (Ca) on hormonal and metabolic milieu of polycystic ovary syndrome (PCOS).Single arm open label trial.Twelve overweight and vitamin D deficient women with PCOS underwent a 2?hour oral glucose tolerance testing at baseline and following 3-month supplementation with vitamin D (daily dose of 3533 IU, increased to 8533 IU after the first five participants) and 530?mg elemental Ca daily.Blood pressure (BP), plasma glucose, insulin, total testosterone (T) androstenedione (A), sex hormone binding globulin, lifestyle parameters were assessed at baseline and following 3-month intervention. Insulin resistance (IR) and area under the curve for glucose and insulin were computed; paired analyses were conducted.Improved serum 25OHD (p < 0.001) and reductions in total T (p = 0.036) and A (p = 0.090) levels were noted following 3-month supplementation, compared to baseline. Significant lowering in BP parameters was seen in participants with baseline BP ? 120/80 mmHg (n = 8) and in those with baseline serum 25OHD ?20?ng/ml (n = 9). Parameters of glucose homeostasis and IR remained unchanged (p > 0.05).Androgen and BP profiles improved followed three month intervention, suggesting therapeutic implications of vitamin D and Ca in overweight and vitamin D deficient women with PCOS.