The comparative effectiveness of 55 interventions in obese patients with polycystic ovary syndrome: A network meta-analysis of 101 randomized trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-age females. The prevalence of obesity in PCOS patients reaches up to 80%, which is 2-fold higher than the general population. OBJECTIVE: The present study aimed to compare the effectiveness of 55 pharmacological interventions across 17 different outcomes in overweight/obese PCOS patients with hyperandrogenism manifestations for both short- and long-term follow-ups. A comprehensive literature search was performed on PubMed, Scopus, Embase, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials comparing any conventional pharmacological intervention as a monotherapy or a combination in overweight/obese patients with polycystic ovary syndrome and hyperandrogenism manifestations. Extracted data included three main parameters; I. Anthropometric parameters (BMI, Waist and Hip circumferences, and Waist/HIP ratio), II. Hormonal parameters (FSH, LH, FSG, SHBG, Estradiol, Total Testosterone, Free testosterone, DHEAS, Androstenedione), and III. Metabolic parameters (Total Cholesterol, LDL-C, HDL-C, Triglycerides, Fasting glucose, Fasting glucose, HOMA-IR). Critical appraisal and risk of bias assessments were performed using the modified Jadad scale, and the overall quality of this network meta-analysis was evaluated according to the CINeMA framework. We performed both a pairwise meta-analysis and a network meta-analysis to evaluate the effect sizes with 95% CI, and we calculated the surface under the cumulative ranking curve (SUCRA) for each intervention. RESULTS: Our final search on May 15th 2021 retrieved 23,305 unique citations from searching six electronic databases. Eventually, 101 RCTs of 108 reports with a total of 8,765 patients were included in our systematic review and multi-treatments meta-analysis. 55 different interventions were included: 22 monotherapies, and 33 combinations. The two-dimensional cluster ranking of the average SUCRA values for metabolic and hormonal parameters with significant estimates revealed flutamide (77.5%, 70%; respectively) as the highest and rosiglitazone (38.2%, 26.3%; respectively) as the lowest, in terms of the overall efficacy in reducing weight and hyperandrogenism. However, cyproterone-acetate+ethinylestradiol exhibited a higher ranking in improving hormonal parameters (71.1%), but even a lower-ranking regarding metabolic parameters (34.5%). CONCLUSIONS AND RELEVANCE: Current evidence demonstrated the superiority of flutamide in improving both metabolic and hormonal parameters, and the higher efficacy of cyproterone-acetate+ethinylestradiol only in improving hormonal parameters. Nearly all interventions were comparable in female hormones, FGS, HDL, glucose, and insulin levels improvements.

The efficacy of vitamin E in reducing non-alcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population. Clinical trials have questioned the role of vitamin E in the treatment of NAFLD with or without other interventions, with still no firm conclusion reached. This study aims to examine the efficiency of vitamin E alone or combined in the management of NAFLD. METHODS: We performed a systematic literature search on PubMed, Scopus, Embase, Ovid, EBSCO host, Science Direct, Web of Science, and Cochrane CENTRAL for randomized controlled trials (RCTs) of the role of vitamin E alone or combined in NAFLD patients. Extracted manuscripts reported data on biochemical, histological, anthropometric, and metabolic outcomes. Baseline characteristics, settings, dosage, and frequency were also collected. RESEARCH: A total of 1317 patients from 15 RCTs were included in our systematic review and meta-analysis. Vitamin E was superior at improving alanine aminotransferase (ALT), aspartate aminotransferase (AST), NAFLD activity score (NAS), and fibrosis in short- and long-term follow up in the adult population, and long-term follow up in the pediatric population. Improvements in metabolic outcomes were best noticed in pediatric patients. Results from multiple regression models showed a significant association between ALT-AST levels and vitamin E dose. AST levels had a significant effect on NAS, and patients with a baseline AST > 50 IU/l showed more promising results. Changes in weight and body mass index (BMI) were strongly associated with changes in NAS. CONCLUSION: Current evidence affirms that vitamin E - whether alone or combined - improves biochemical and histological outcomes in adults and pediatric patients.