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.
Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting about 10% of women in reproductive age and associated with a variety of hormonal abnormalities, including hyperandrogenemia and infertility, all of which could lead to PCOS. Statins were previously introduced as a therapeutic option for reducing testosterone levels in women with PCOS, either alone or in combination. The aim of this study is to evaluate the effectiveness of different statins alone or in combination with metformin in reducing testosterone levels in women with PCOS. METHODS:Medline, Embase, and clinicaltrials.gov were searched for studies that investigated the efficacy of statins, metformin, spironolactone, or combined oral contraceptives (COCs), individually or in combination, in reducing the testosterone level in patients with PCOS. The search was limited to randomized clinical trials and conducted according to the preferred reporting items for systematic reviews and meta-analyses - extension statement for network meta-analyses (PRISMA-NMA). The quality of included studies was assessed using the Cochrane Collaboration risk of bias (RoB) assessment tool. A frequentist network meta-analysis using random-effects models was used to assess the efficacy in reducing testosterone level and were expressed as odds ratios (OR) and 95% credible interval (95%Crl). All statistical analyses were performed using netmeta Version 1.0 on R statistical package. RESULT:Nine RCTs involving 613 patients were included. Atorvastatin showed greater reduction in testosterone level compared to COC (MD -2.78, 95%CrI -3.60, -1.97), spironolactone plus metformin (MD -2.83, 95%CrI -3.80, -1.87), simvastatin (MD -2.88, 95%CrI -3.85, -1.92), spironolactone (MD -2.90, 95%CI -3.77, -2.02), simvastatin plus metformin (MD -2.93, 95%CrI -3.79, -2.06), metformin (MD -2.97, 95%CrI -3.69, -2.25), lifestyle modification (MD -3.02, 95%CrI -3.87, -2.18), and placebo (MD -3.04, 95%CrI -3.56, -2.53). CONCLUSION:Atorvastatin was found to be more effective than the other management strategies in reducing the total testosterone level for patients with PCOS. Future studies should focus on the optimal dose.
Project description:BACKGROUND/OBJECTIVES:Prebiotics are increasingly recognized as an effective measure to promote health and prevent adverse health outcomes in preterm infants. We aimed to systematically review the randomized controlled trials (RCTs) in this area. SUBJECTS/METHODS:Relevant studies from January 2000 to June 2018 were searched and selected from PubMed, Medline, Scopus, and the Cochrane Library. RCTs were included if they involved preterm infant participants, included a prebiotic intervention group, measured incidence of sepsis, feeding intolerance, mortality, time to full enteral feeding, necrotizing enterocolitis (NEC), length of hospital stay, and stool frequency as outcomes. RESULTS:Eighteen RCTs (n?=?1322) were included in the final meta-analysis. Participants who took prebiotics showed significant decreases in the incidence of sepsis (with a risk ratio (RR) of 0.64, 95% CI: 0.51, 0.78), mortality (RR?=?0.58. 95% CI: 0.36, 0.94), length of hospital stay (mean difference (MD): -5.18, 95% CI: -8.94, -1.11), and time to full enteral feeding (MD: -0.99, 95% CI: -1.15, 0.83). The pooled effects showed no significant differences between intervention and control groups in relation to the morbidity rate of NEC (RR?=?0.79, 95% CI: 0.44, 1.44) or feeding intolerance (RR?=?0.87, 95% CI: 0.52, 1.45). CONCLUSIONS:The results showed that the use of prebiotics with preterm infants is safe and can decrease the incidence of sepsis, mortality, length of hospital stay, and time to full enteral feeding but not NEC.
Project description:To compare the efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus (GDM), a meta-analysis of randomized controlled trials (RCTs) was conducted. PubMed, Embase, CINAHL, Web of Science, and Cochrane Library to November 13, 2018, were searched for RCT adjusted estimates of the efficacy and safety of metformin, glyburide, and insulin treatments in GDM patients. There were 41 studies involving 7703 GDM patients which were included in this meta-analysis; 12 primary outcomes and 24 secondary outcomes were detected and analyzed. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (RR, 0.57; 95% CI, 0.45 to 0.72; P < 0.001), NICU admission (RR, 0.75; 95% CI, 0.64 to 0.87; P < 0.001), neonatal hypoglycemia (RR, 0.57; 95% CI, 0.49 to 0.66; P < 0.001), and macrosomia (RR, 0.68; 95% CI, 0.55 to 0.86; P < 0.05). To the outcomes of birth weight and gestational age at delivery, insulin had a significant increase when compared with metformin (MD, 114.48; 95% CI, 37.32 to 191.64; P < 0.01; MD, 0.23; 95% CI, 0.12 to 0.34; P < 0.001; respectively). Of the two groups between glyburide and metformin, metformin had lower gestational weight gain compared with glyburide (MD, 1.67; 95% CI, 0.26 to 3.07; P < 0.05). Glyburide had a higher risk of neonatal hypoglycemia compared with insulin (RR, 1.76; 95% CI, 1.32 to 2.36; P < 0.001). This meta-analysis found that metformin could be a safe and effective treatment for GDM. However, clinicians should pay attention on the long-term offspring outcomes of the relative data with GDM patients treated with metformin. Compared with insulin, glyburide had a higher increase of neonatal hypoglycemia. The use of glyburide in pregnancy for GDM women appears to be unclear.
Project description:<h4>Background</h4>Polycystic ovary syndrome (PCOS) is one of the most common disorders of reproductive endocrinology in women of reproductive age. Lifestyle intervention and oral contraceptives are the first-line treatments for PCOS. Recent studies have suggested that complementary and alternative medicine (CAM) therapies including acupuncture, herbal medicine, and mind-body therapy have the potential to alleviate the symptoms and/or pathology of PCOS and to improve the quality of life of women with PCOS. This meta-analysis aimed to quantitatively summarize the efficacy and safety of moxibustion combined with oriental herbal medicine (OHM), common CAM therapies, for treating PCOS.<h4>Methods</h4>Four databases were searched from their inception to June 22, 2018. Randomized controlled trials (RCTs) and quasi-RCTs using both OHM and moxibustion as experimental intervention, and western medication (WM) as control intervention were included. Studies involving OHM plus moxibustion combined with WM as the experimental intervention were also included. The quality of included studies was assessed using risk of bias tool.<h4>Results</h4>Owing to the heterogeneity of reporting, meta-analysis was only performed for pregnancy rate, rate of normal biphasic basal body temperature (BBT), and total effective rate (TER). The results showed that compared to the WM group, the OHM combined with moxibustion group was associated with significantly higher pregnancy rate (risk ratio [RR] 1.95, 95% confidence interval [CI] 1.55-2.47; I?=?0%), normal biphasic BBT rate (RR 1.66, 95% CI 1.34-2.05; I?=?0%), and TER (RR 1.19, 95% CI 1.08-1.31; I?=?0%). When OHM combined with moxibustion was used as an adjunctive therapy to WM, pregnancy rate (RR 1.65, 95% CI 1.29-2.11; I?=?0%), and TER (RR 1.35, 95% CI 1.13-1.61; I?=?43%) were significantly higher than those of the WM group.<h4>Conclusion</h4>According to current evidence, OHM combined with moxibustion might be beneficial for treating PCOS. Moreover, the treatment might improve the therapeutic effects of conventional WMs including clomiphene citrate, oral contraceptives, and/or metformin. However, the findings should be interpreted with caution, owing to poor methodological quality of the included studies. Further larger, high-quality, rigorous RCTs should be conducted in this regard.
Project description:<h4>Background</h4>Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes.<h4>Aims</h4>To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy.<h4>Methods</h4>PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24?26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed.<h4>Results</h4>In 4 RCTs (<i>n</i> = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); -0.55% (-0.67, -0.43)) and weight (-2.00 kg (-2.34, -1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (-0.59% (-0.72, -0.46)) and weight (-0.57 kg (-0.89, -0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; -0.47 kg (-0.88, -0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy.<h4>Conclusions</h4>Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.
Project description:OBJECTIVE:We evaluated current evidence from randomised controlled trials (RCTs) regarding the effectiveness of chemical peeling for treating acne vulgaris. METHODS:Standard Cochrane methodological procedures were used. We searched MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE via OvidSP through April 2017. Reviewers independently assessed eligibility, risk of bias and extracted data. RESULTS:Twelve RCTs (387 participants) were included. Effectiveness was not significantly different: trichloroacetic acid versus salicylic acid (SA) (percentage of total improvement: risk ratio (RR) 0.89; 95% CI 0.73 to 1.10), glycolic acid (GA) versus amino fruit acid (the reduction of inflammatory lesions: mean difference (MD), 0.20; 95%?CI -3.03 to 3.43), SA versus pyruvic acid (excellent or good improvement: RR 1.11; 95%?CI 0.73 to 1.69), GA versus SA (good or fair improvement: RR 1.00; 95%?CI 0.85 to 1.18), GA versus Jessner's solution (JS) (self-reported improvements: RR 1.00; 95%?CI 0.44 to 2.26), and lipohydroxy acid versus SA (reduction of non-inflammatory lesions: 55.6%vs48.5%, p=0.878). Combined SA and mandelic acid peeling was superior to GA peeling (percentage of improvement in total acne score: 85.3%vs68.5%, p<0.001). GA peeling was superior to placebo (excellent or good improvement: RR 2.30; 95%?CI 1.40 to 3.77). SA peeling may be superior to JS peeling for comedones (reduction of comedones: 53.4%vs26.3%, p=0.001) but less effective than phototherapy for pustules (number of pustules: MD -7.00; 95%?CI -10.84 to -3.16). LIMITATIONS:The methodological quality of the included RCTs was very low to moderate. Meta-analysis was not possible due to the significant clinical heterogeneity across studies. CONCLUSION:Commonly used chemical peels appear to be similarly effective for mild-to-moderate acne vulgaris and well tolerated. However, based on current limited evidence, a robust conclusion cannot be drawn regarding any definitive superiority or equality among the currently used chemical peels. Well-designed RCTs are needed to identify optimal regimens.
Project description:Background: Chinese patent medicine Tongxinluo capsule (TXL) is commonly used for cardio-cerebrovascular diseases. Previous research had demonstrated that TXL exhibited great clinical effects on the treatment of acute myocardial infarction (AMI), however there is a lack of systematic review. The purpose of this study was to evaluate the potential effectiveness and safety of TXL for secondary prevention in patients with AMI. Method: We searched 6 databases to identify relevant randomized controlled trials (RCTs) from inceptions to December 30, 2017. Two review authors independently assessed the methodological quality and analyzed data by the RevMan 5.3 software. The publication bias was assessed through funnel plot and Begg's test. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for evaluating the quality of evidence. Results: We included 19 RCTs in this review and performed a meta-analysis based on 16 studies. There were statistical differences of TXL treatment group in reducing primary cardiovascular events (cardiac death [RR = 0.27, 95%CI: 0.08~0.95, I2 = 0%], recurrent myocardial reinfarction [RR = 0.38, 95%CI: 0.20~0.74, I2 = 0%], arrhythmia [RR = 0.44, 95%CI: 0.30~0.66, I2 = 0%], recurrent angina pectoris [RR = 0.34, 95%CI: 0.17~0.69, I2 = 0%]). TXL could improve cardiac function (LVEF [MD = 4.10, 95%CI: 3.95~4.25, I2 = 0%]), regulate blood lipid TC [MD = -0.66, 95%CI: -0.94 ~ -0.37, I2 = 74%], TG [MD = -0.38, 95%CI: -0.62 ~ -0.14, I2 = 70%], LDL-C[-0.40, 95%CI: -0.65 ~ -0.16, I2 = 88%), decrease the level of hs-CRP (4-week: MD = -0.78, 95%CI: -0.97 ~ -0.60, I2 = 20%; Over 4-week: MD = -1.36, 95%CI: -1.55 ~ -1.17, I2 = 20%). However, TXL has little effects on revascularization [RR = 0.45, 95%CI: 0.13~1.56, I2 = 0%], recurrent heart failure (RR = 0.83, 95%CI: 0.27~2.57, I2 = 0%), and HDL-C (MD = 0.14, 95%CI: 0.00 ~0.29, I2 = 73%). Furthermore, TXL treatment group was more prone to suffer gastrointestinal discomfort. Conclusion: Chinese patent medicine TXL seemed beneficial for secondary prevention after AMI. This potential benefit needs to be further assessed through more rigorous RCTs. Systematic review registration number in the PROSPERO register: CRD42017068417.
Project description:Objective:The purpose of this study was to assess the effectiveness and safety of acupuncture for functional constipation (FC). Methods:A rigorous literature search was performed in English (PubMed, Web of Science, the Cochrane Library, and EMBASE) and Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), Wanfang database, and China Science and Technology Journal (VIP)) electronic databases from their inception to October 2019. Included randomized controlled trials (RCTs) compared acupuncture therapy with sham acupuncture or pharmacological therapies. The outcome measures were evaluated, including the primary outcome of complete spontaneous bowel movement (CSBM) and secondary outcomes of Bristol Stool Form Scale (BSFS), constipation symptoms scores (CSS), responder rate, the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, and safety evaluation. Meta-analysis was performed by using RevMan5.3. Results:The merged data of 28 RCTs with 3525 participants indicated that acupuncture may be efficient for FC by increasing CSBMs (p < 0.00001; MD?=?0.84 [95% CI, 0.65 to 1.03]; I 2?=?0%) and improving constipation symptoms (p=0.03; SMD?=?-0.4 [95% CI, -0.78 to -0.03]; I 2?=?74%), stool formation (p < 0.00001; MD?=?0.24 [95% CI, 0.15 to 0.34]; I 2?=?0%), quality of life (p < 0.00001; N?=?1, MD?=?-0.33 [95% CI, -0.45 to -0.21]), and responder rates (p=0.02; RR?=?2.16; [95% CI, 1.1 to 4.24]; I 2?=?69%) compared with the effects of sham treatment. No increased risk of adverse events was observed (p=0.44; RR?=?1.18; [95% CI, 0.77 to 1.81]; I 2?=?0%). With regard to medication comparisons, the pooled data indicated that acupuncture was more effective in increasing CSBMs (p=0.004; MD?=?0.53 [95% CI, 0.17 to 0.88]; I 2?=?88%) and improving patients' quality of life (p < 0.00001; SMD?=?-0.73 [95% CI, -1.02 to -0.44]; I 2?=?64%), with high heterogeneity. However, there were no significant differences in responder rate (p=0.12; RR?=?1.31; [95% CI, 0.94 to 1.82]; I 2?=?53%), BSFS (p=0.5; MD?=?0.17 [95% CI, -0.33 to 0.68]; I 2?=?93%), or CSS (p=0.05; SMD?=?-0.62 [95% CI, -1.23 to -0.01]; I 2?=?89%). Regarding safety evaluation, acupuncture was safer than medications (p < 0.0001; RR?=?0.3; [95% CI, 0.18 to 0.52]; I 2?=?30%). Conclusions:Current evidence suggests that acupuncture is an efficient and safe treatment for FC. Acupuncture increased stool frequency, improved stool formation, alleviated constipation symptoms, and improved quality of life. However, the evidence quality was relatively low and the relationship between acupuncture and drugs is not clear. More high-quality trials are recommended in the future. PROSPERO registration number: CRD42019143347.
Project description:OBJECTIVE:To evaluate whether conventional postoperative drainage is more effective than not providing drainage in patients with non-complicated benign gallbladder disease following laparoscopic cholecystectomy (LC). METHODS:A search of the electronic databases MEDLINE, EMBASE, Web of science, Cochrane Library, and Chinese Biomedical Database (CBM) was conducted for randomized controlled trials (RCTs) reporting outcomes of LC surgery with and without an abdominal drain. RESULTS:Twenty-one RCTs involving 3246 patients (1666 with drains vs 1580 without) were included in the meta-analysis. There were no statistically significant differences in the rates of incidence of intra-abdominal fluid (RR: 1.10; 95% CI: 0.81-1.49; P?=?.54) or post-surgical mortality (RR: 0.44; 95% CI: 0.04-4.72; P?=?.50) between the two groups. Abdominal drains did not reduce the overall incidence of nausea and vomiting (RR: 1.16; 95% CI: 0.95-1.42; P?=?.15) or shoulder tip pain (RR: 1.03; 95% CI: 0.76-1.38; P?=?.86). The abdominal drain group displayed significantly higher pain scores (MD: 1.07; 95% CI: 0.69-1.46; P?<?.001) than the non-drainage patients. Abdominal drains prolonged the duration of the surgical procedure (MD: 5.69?min; 95% CI: 2.51-8.87; P?=?.005) and postoperative hospital stay (MD: 0.47 day; 95% CI: 0.14-0.80; P?=?.005). Wound infection was found to be associated with the use of abdominal drains (RR: 1.97; 95% CI: 1.11-3.47; P?=?.02). CONCLUSIONS:Currently, there is no evidence to support the use of routine drainage after LC in non-complicated benign gallbladder disease. Further well-designed randomized clinical trials are required to confirm this finding.
Project description:OBJECTIVE:To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). METHODS:A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs). RESULTS:Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c <7% (RR 1.64, 95% CI 1.53 to 1.75). When combined with submaximal-dose metformin, saxagliptin significantly increased the proportion of patients achieving HbA1c <7% compared with acarbose (RR 2.38, 95% CI 1.17 to 4.83) and uptitrated metformin (RR 1.30, 95% CI 1.04 to 1.63). Saxagliptin was similar to other DPP-4 inhibitors but inferior to liraglutide and dapagliflozin on glycemic control. Saxagliptin significantly decreased the incidences of overall adverse events compared with acarbose (RR 0.71, 95% CI 0.57 to 0.89) and liraglutide (RR 0.41, 95% CI 0.24 to 0.71) when added to metformin. Weight gain and hypoglycemia with saxagliptin was slightly but significantly higher than placebo and lower than sulfonylureas. Saxagliptin did not increase the risk of arthralgia, heart failure, pancreatitis and other adverse events. CONCLUSIONS:Generally, saxagliptin has similar efficacy compared with most oral antidiabetic drugs and may be more effective than acarbose, while having a better safety profile than both acarbose and sulfonylureas.