The efficacy and safety of metformin combined with simvastatin in the treatment of polycystic ovary syndrome: A meta-analysis and systematic review

Background:Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS.Methods:We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects.Results:Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD –2.66, 95% CI –3.65 to –1.66), triglycerides (SMD –1.25, 95% CI –2.02 to –0.49), low density lipoprotein (SMD –2.91, 95% CI –3.98 to –1.84), testosterone (SMD –0.64, 95% CI –1.13 to –0.15), fasting insulin (SMD –1.17, 95% CI –2.09 to –0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD –0.05, 95% CI –0.56–0.46), luteinizing hormone (SMD –0.58, 95% CI –1.66 to –0.50), follicle stimulating hormone (SMD 0.41, 95% CI –0.78–1.59), prolactin (SMD –1.38, 95% CI –2.93–0.17), fasting blood sugar (SMD 0.23, 95% CI –0.52–0.97), and insulin sensitivity index (SMD –0.17, 95% CI –0.48–0.15) between experimental and control groups (all P > .05).Conclusions:Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples.     

Tanshinone for polycystic ovary syndrome: A protocol of systematic review and meta-analysis

Backgrounds:Polycystic ovary syndrome (PCOS) constitutes an endocrine and metabolic disorder characterized by hyperandrogenemia, ovulation disorders, and polycystic ovary. Existing therapy is low efficacy and has significant side effects. In traditional Chinese medicine, tanshinone was used for PCOS women. Here, we will investigate the safety, as well as the efficacy of tanshinone in treating polycystic ovary syndrome.Methods:Two researchers will independently research eligible randomized controlled trials in 6 repositories: PubMed, CINAHL, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), as well as Cochrane Library, from their onset to present. The languages will constitute either English or Chinese, and we will carry out article selection, data mining, and conduct an evaluation of the risk of bias by the Cochrane tool of risk of bias. All analyses will be conducted by using the Cochrane Review Manager software (RevMan 5.3).Results and conclusion:This study will provide the latest research evidence on the efficacy, as well as safety of tanshinone for PCOS patients.Registration number:INPLASY2020100017     

The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis

While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone‐binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment‐insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total‐cholesterol and low‐density lipoprotein‐cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.     

Efficacy and safety of moxibustion in the treatment of infertility with polycystic ovary syndrome: A protocol of systematic review and meta-analysis

Background:Polycystic ovary syndrome (PCOS) is one of the common diseases of reproductive endocrine metabolism in gynecology, and it is also a common and difficult disease affecting female reproductive endocrine health. PCOS characterized by insulin resistance and hyperandrogenemia, the clinical manifestations are polychaemia, acne, obesity, infertility, menstrual disorders and so on. Clinical treatment of patients with PCOS ovulatory dysfunction infertility is mainly treated with ovulation-promoting drugs, insulin sensitizer, hyperandrogenemia drugs and other drugs Healing. It is found that the sensitivity of patients to ovulation promotion is poor, and it is often necessary to increase the dosage of drugs to increase ovulation rate, thus increasing the risk of ovarian hyperstimulation syndrome, and the recurrence rate is higher after withdrawal. Moxibustion therapy has shown strong advantages in the treatment of PCOS, and the curative effect is accurate. Therefore, this paper will carry out a systematic evaluation and meta-analysis of the efficacy and safety of moxibustion therapy in the treatment of PCOS.Methods:We will search 8 electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database (WF), and Chinese Biomedical Literature Database (CBM). We will search above electronic databases from the beginning to January 2021, without any language restriction. Ovulation rate and pregnancy rate will be accepted as the primary outcomes. The changes of Sex hormone levels, including Luteinizing hormone, follicle-stimulating hormone, serum estradiol, total testosterone will be used as secondary outcomes. RevMan 5.3 software will be used for statistical analysis. The result about the curative effect and safety of moxibustion therapy for PCOS will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data.Results:Only when we finish this meta-analysis can we get the result.Conclusions:The results of this study will provide reliable evidence for the efficacy and safety of moxibustion therapy in the treatment of PCOS.     

Evidence summaries and recommendations from the international evidence‐based guideline for the assessment and management of polycystic ovary syndrome: Lifestyle management

Lifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first‐line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence‐based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence‐based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence‐based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first‐line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers.     

The therapeutic effects of glucagon-like peptide-1 receptor agonists and metformin on polycystic ovary syndrome: A protocol for systematic review and meta-analysis

Background:Obesity and insulin resistance (IR) are common in polycystic ovary syndrome (PCOS), which contribute to reproductive and metabolic abnormalities. Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss. Recent studies have reported that glucagon-like peptide 1 (GLP-1) receptor agonists improve IR and reduce weight in women with PCOS. We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes.Methods:Databases including PubMed, EMBASE, Web of Science, and Cochrane Library were selected to search for randomized controlled trials (RCTs) published in English up to March 2020. Eligible studies were identified according to the inclusion criteria. The primary outcomes included menstrual frequency, body mass index (BMI), total testosterone, and the homeostatic model assessment of insulin resistance. GRADE criteria were implemented to assess the quality of evidence for primary outcomes.Results:Seven RCTs were selected for analysis, comprising 464 overweight/obese women with PCOS. In the low-quality evidence, a meta-analysis demonstrated that GLP-1 receptor agonists showed better effects relative to metformin on the reduction of body mass index (mean difference − 1.72; 95% confidence interval −2.46 to −0.99, P < .001) and homeostatic model assessment of insulin resistance (standard mean difference −0.37; 95% confidence interval − 0.60,− 0.15, P = .001). Moreover, the combination therapy exhibited similar effects on primary outcomes relative to GLP-1 receptor agonist alone. GLP-1 receptor agonists were also found to be associated with lower abdominal girth compared to metformin. A meta-analysis of gastrointestinal discomfort showed no significant difference between GLP-1 receptor agonist and metformin therapies, and between the combination therapy and GLP-1 receptor agonist alone.Conclusions:GLP-1 receptor agonists appear to be more beneficial for weight loss and IR improvement compared to metformin for overweight/obese women with PCOS. However, the combination treatment displays comparable effects with GLP-1 receptor agonist alone. The incidence of gastrointestinal discomforts was similar in different groups. However, the quality of the body of evidence is “low.” Further prospective RCTs and cost-effectiveness analyses are also warranted to guide GLP-1 receptor agonists to treat women with PCOS.     

The role of maternal obesity in infant outcomes in polycystic ovary syndrome—A systematic review,meta‐analysis,and meta‐regression

Polycystic ovary syndrome (PCOS) is associated with worsened pregnancy and infant outcomes, higher body mass index (BMI), and longitudinal weight gain. Despite most of the clinical features of PCOS being risk factors for worsened infant outcomes in the general population, their impact on infant outcomes in PCOS is unknown. We aimed to investigate the association of PCOS with infant outcomes considering maternal adiposity, other known risk factors, and potential confounders. The meta‐analyses included 42 studies in 7041 women with PCOS and 63 722 women without PCOS. PCOS was associated with higher gestational weight gain (GWG) and with higher preterm birth and large for gestational age and with lower birth weight with this association varying by geographic continent, PCOS phenotypes, and study quality. However, PCOS was associated with none of these outcomes on BMI‐matched studies. Gestational diabetes was significantly associated with an increased preterm birth on meta‐regression. We report for the first time that GWG is higher in PCOS. Infant outcomes vary by geographic continent and study quality but are similar in BMI‐matched women with and without PCOS. This suggests that infant outcomes in PCOS may be related to maternal obesity. These novel findings warrant future studies in PCOS investigating screening and management of infant outcomes with consideration of maternal obesity.     

Intelligence in relation to obesity: a systematic review and meta‐analysis

We performed a systematic review describing obesity/intelligent quotient (IQ) association, particularly childhood IQ in relation to adulthood obesity. After screening 883 citations from five electronic databases, we included 26 studies, most of medium quality. The weighted mean difference (WMD) of the full IQ (FIQ)/obesity association in the pre‐school children was ?15.1 (P > 0.05). Compared with controls, the WMD of FIQ and performance IQ of obese children were ?2.8 and ?10.0, respectively (P < 0.05), and the WMD of verbal IQ was ?7.01 (P > 0.05). With increasing obesity, the FIQ in pre‐school children declined, with a significant difference for severely obese children and FIQ. In pubertal children, a slightly different effect of FIQ and obesity emerged. Two studies reported an inverse FIQ/obesity association in adults, but it was non‐significant after adjusting for educational attainment. Four papers found that childhood FIQ was inversely associated with adult body mass index, but after adjusting for education, became null. Overall there was an inverse FIQ/obesity association, except in pre‐school children. However, after adjusting for educational attainment, FIQ/obesity association was not significantly different. A lower FIQ in childhood was associated with obesity in later adulthood perhaps with educational level mediating the persistence of obesity in later life.     

Association between duration of oral contraceptive use and risk of hypertension: A meta‐analysis

A meta‐analysis was conducted to evaluate the association between duration of oral contraceptive use and risk of hypertension. Relevant studies published in English or Chinese were identified by a search of PubMed, Web of Science, Wanfang Database, and China National Knowledge Infrastructure to January 2017. Seventeen articles containing 24 studies with 270,284 participants were included in this meta‐analysis. The pooled relative risk of hypertension for the highest vs lowest category of oral contraceptive duration was 1.47 (95% confidence interval, 1.25–1.73), and excluding three studies with a relative risk >3.0 yielded a pooled relative risk of 1.26 (95% confidence interval, 1.11–1.44). A linear dose‐response relationship was found (P_nonlinearity=0.69) and the risk of hypertension increased by 13% (relative risk, 1.13; 95% confidence interval, 1.03–1.25) for every 5‐year increment in oral contraceptive use. The duration of oral contraceptive use was positively associated with the risk of hypertension in this meta‐analysis.     

Systematic review with meta‐analyses of studies on the association between cirrhosis and liver metastases

The hemodynamic, cellular and metabolic changes seen in patients with cirrhosis may reduce the risk of liver metastases. The aim of this case–control is to compare the risk of liver metastases from extrahepatic malignant diseases among patients with or without cirrhosis. Electronic searches (Medline, Embase, and Web of Science) and manual searches were combined (October 2010) to identify observational studies on patients with malignant disease reporting the risk of liver metastases among cases (with cirrhosis) and controls (without liver disease). Meta‐analysis was performed using random effects models due to an expected clinical heterogeneity. Sixteen studies were included. Evidence of liver metastases was diagnosed in 22% of cases and 38% of controls based on autopsies (n = 14 studies) or laparoscopy (n = 2 studies). Random effects meta‐analysis suggested that patients with cirrhosis had a lower risk of liver metastases (relative risk = 0.53; 95% confidence interval = 0.42–0.66). The conclusions were confirmed in sensitivity and subgroup analyses accounting for the year of publication, matching for age, sex and location of tumors (within the portal vein). No statistical evidence of bias was identified and the analyses were confirmed when adjusting for multiple testing. The present review suggests that cirrhosis reduces the risk of liver metastases. However, additional evidence from prospective studies adjusting for confounding factors is still needed.