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The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials.

ABSTRACT: Purpose:To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS). Methods:PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huangliansu (in Chinese)/Xiao bojian (in Chinese)" till 30 May 2019. Relevant indicators were collected and the data were analyzed by using RevMan 5.3 software. Results:Eventually, a total of 12 randomized controlled trials were included in this systematic review. Our study suggested that berberine had similar live birth rates compared with placebo or metformin and lower live birth rates (RR: 0.61, 95% CI: 0.44 to 0.82) compared with letrozole. There was a significant difference between berberine and placebo and between berberine and no treatment in terms of decreasing total testosterone and luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio (8 RCTs, 577 participants, MD: -0.34, 95% CI: -0.47 to -0.20; 3 RCTs, 179 participants, MD: -0.44, 95% CI: -0.68 to -0.21, respectively). Berberine was associated with decreasing total cholesterol (3 RCTs, 201 participants; MD: -0.44, 95% CI: -0.60 to -0.29), waist circumference (3 RCTs, 197 participants, MD: -2.74, 95% CI: -4.55 to -0.93), and waist-to-hip ratio (4 RCTs, 258 participants, MD: -0.04, 95% CI: -0.05 to -0.03) compared with metformin, but not with improved BMI (4 RCTs, 262 participants, MD: -0.03, 95% CI: -0.46 to 0.39). Berberine did not increase the incidence of gastrointestinal adverse events (3 RCTs, 567 participants, RR: 1.01, 95% CI: 0.76 to 1.35) or serious events during pregnancy (RR: 0.98, 95% CI: 0.70 to 1.37) compared with placebo. Conclusion:This review found no solid evidence that berberine could improve live birth or other clinical outcomes in women with PCOS. However, berberine appeared to be more efficacious for improving insulin resistance and dyslipidemia and decreasing androgen levels and LH/FSH ratio in women with PCOS when compared with metformin.

SUBMITTER: Xie L

PROVIDER: S-EPMC6930782 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Xie Liangzhen L Zhang Duojia D Ma Hongli H He Hui H Xia Qing Q Shen Wenjuan W Chang Hui H Deng Yingying Y Wu Qi Q Cong Jing J Wang Chi Chiu CC Wu Xiaoke X

Evidence-based complementary and alternative medicine : eCAM 20191213

<h4>Purpose</h4>To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS).<h4>Methods</h4>PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huanglians ...[more]

PMID: 31915452

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Project description:IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathy in women of reproductive age. Recently, moxibustion, as a complementary and alternative therapy, has been commonly used in assisted reproduction and improvement of metabolic abnormalities in patients with PCOS. Currently, intervention efficacy of the use of moxibustion in PCOS treatment still remains controversial due to lack of high-quality evidence. Consequently, this study protocol was designed to objectively review and evaluate the effectiveness and safety of moxibustion treatment for PCOS.Methods and analysisElectronic searches will be carried out from inception to May 2021 in the online databases of The Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature, Chongqing VIP Chinese Science and Technology Periodical Database (VIP) and China National Knowledge Infrastructure. The Chinese Clinical Trial Registry Center and Clinical Trials will be used for searching ongoing trials. Randomised controlled trials and the first period in randomised cross-over trials involving any type of moxibustion for patients with PCOS will be included. Primary outcomes will be the ovulation rate, pregnancy rate and sex hormone levels, and secondary outcomes will be changes in clinical symptoms and metabolic indicators, total effective rate and the incidences of side effects and adverse events. Briefly, two reviewers will independently conduct study selection and data extraction, and the risk of bias will be assessed. Prior to the formal meta-analysis, the heterogeneity of included studies will be assessed. Review Manager Statistical Software (RevMan) V.5.3 will be used for data processing. Finally, the Grading of Recommendations Assessment, Development and Evaluation method will be applied to evaluate the quality of evidence.Ethics and disseminationEthical approval is not necessary since this study is designed as a systematic review. This study will be disseminated by a peer-review journal or conference presentation.

Project description:Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting up to 15% of women at reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including hyperinsulinemia and insulin resistance and a 4-fold increased risk of developing type 2 diabetes. Despite the high prevalence the pathophysiology of the syndrome is unclear. Insulin resistance in women with PCOS likely affect the skeletal muscle and recently it was demonstrated that changes in DNA methylation affects the gene expression in skeletal muscle that in part can explain their metabolic abnormalities. The objective of this work was to combine gene expression array data from different datasets to improve statistical power and thereby identify novel biomarkers that can be further explored. In this narrative review, we performed a meta-analysis of skeletal muscle arrays available from Gene Expression Omnibus and from publications. The eligibility criteria were published articles in English, and baseline (no treatment) skeletal muscle samples from women with PCOS and controls. The R package Metafor was used for integration of the datasets. One hundred and fourteen unique transcripts were differentially expressed in skeletal muscle from women with PCOS vs. controls (q < 0.05), 87% of these transcripts have not been previously identified as altered in PCOS muscle. ING2, CDKAL1, and AKTIP had the largest differential increase in expression, and TSHZ2, FKBP2, and OCEL1 had the largest decrease in expression. Two genes, IRX3 and CDKAL1 were consistently upregulated (q < 0.05) in the individual analyses and meta-analysis. Based on the meta-analysis, we identified several dysregulated immunometabolic pathways as a part of the molecular mechanisms of insulin resistance in the skeletal muscle of women with PCOS. The transcriptomic data need to be verified by functional analyses as well as proteomics to advance our understanding of PCOS specific insulin resistance in skeletal muscle.

Project description:ObjectiveTo study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS).MethodsSelected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine.ResultsIn the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells.ConclusionIn this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.

Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.

Project description:BackgroundPolycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.ObjectivesTo assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.Search methodsWe searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.Selection criteriaRandomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.Data collection and analysisTwo authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).Main resultsWe included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence).Authors' conclusionsLifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.

Dataset Information

The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Publications

The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Similar Datasets

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