Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis
TL;DR: Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess, and this finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.
Abstract: BACKGROUND Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relatively small studies published to date do not permit reaching a definitive conclusion. We aimed at conducting a systematic review and meta-analysis of studies evaluating circulating markers of oxidative stress in patients with PCOS. METHODS We conducted a systematic review of studies reporting circulating markers of oxidative stress in women with PCOS and controls published up to June 2012, using Entrez PubMed and EMBASE online facilities. Meta-analysis calculated standardized mean differences (SMDs) and 95% confidence intervals (95CI). RESULTS From 1633 potential studies identified electronically, 68 studies, including 4933 PCOS patients and 3671 controls, were selected. For each of nine circulating markers of oxidative stress, an individual meta-analysis was conducted. Compared with control women, patients with PCOS presented higher circulating concentrations of homocysteine (23% increase, SMD 0.6, 95CI, 0.4-0.8), malondialdehyde (47% increase, SMD 1.9, 95CI 1.2-2.6) and asymmetric dimethylarginine (36% increase, SMD 1.1, 95CI 0.6-1.6), and increased superoxide dismutase activity (34% increase, SMD 1.0, 95CI 0.5-1.4) and decreased glutathione levels (50% decrease, SMD -3.7, 95CI -6.2 to -1.2) and paraoxonase-1 activity (32% decrease, SMD -0.9, 95CI -1.3 to -0.4). Similar results were found when restricting the analyses to studies in which patients and controls were matched for age and body mass index. CONCLUSIONS Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess. This finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.
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01 Jul 1989
TL;DR: It is suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria for ovarian polycystosis.
Abstract: Due to the comprehensive examination of 50 patients with ovarian polycystosis the authors suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria.
1,022 citations
TL;DR: It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others, and the vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker.
Abstract: Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clin...
571 citations
Cites background from "Circulating markers of oxidative st..."
...Three meta-analyses confirmed a decrease in plasma GSH and an increase in plasma GSSG in patients with autism spectrum disorders (54) and lower plasma GSH levels in polycystic ovary syndrome (121), two conditions in which oxidative stress has been implicated (127, 144)....
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TL;DR: The clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.
Abstract: Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.
505 citations
TL;DR: A critical endocrine and European perspective on the debate on the definition of PCOS is offered and all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder are summarized.
Abstract: Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
491 citations
TL;DR: Polycystic ovary syndrome is a complex endocrine disorder affecting 5–10 % of women of reproductive age and patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.
Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5–10 % of women of reproductive age. It generally manifests with oligo/anovulatory cycles, hirsutism and polycystic ovaries, together with a considerable prevalence of insulin resistance. Although the aetiology of the syndrome is not completely understood yet, PCOS is considered a multifactorial disorder with various genetic, endocrine and environmental abnormalities. Moreover, PCOS patients have a higher risk of metabolic and cardiovascular diseases and their related morbidity, if compared to the general population.
283 citations
Cites background from "Circulating markers of oxidative st..."
...Lower level of APMAP has been found in visceral adipose tissue in patients with PCOS [81] might contribute to the impairment in antioxidant defense characteristic of PCOS [86]....
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References
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TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
"Circulating markers of oxidative st..." refers methods in this paper
...Evidence dissemination bias was estimated by funnel plot asymmetry and Egger’s regression test (Egger et al., 1997) when 10 or more studies were analysed....
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TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
"Circulating markers of oxidative st..." refers methods in this paper
...…resulting from clinical and/or methodological issues might have had on the results of the meta-analyses we chose Hedges’s g SMD as a measure of the effect size (Durlak, 2009) and implemented random-effects models using the DerSimonian–Laird weighting method (DerSimonian and Laird, 1986)....
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...In order to overcome the impact that the heterogeneity resulting from clinical and/or methodological issues might have had on the results of the meta-analyses we chose Hedges’s g SMD as a measure of the effect size (Durlak, 2009) and implemented random-effects models using the DerSimonian–Laird weighting method (DerSimonian and Laird, 1986)....
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01 Jan 2014
TL;DR: The Newcastle-Ottawa Scale (NOS) as discussed by the authors was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results.
Abstract: Nonrandomised studies, including case-control and cohort studies, can be challenging to implement and conduct. Assessment of the quality of such studies is essential for a proper understanding of nonrandomised studies. The Newcastle-Ottawa Scale (NOS) is an ongoing collaboration between the Universities of Newcastle, Australia and Ottawa, Canada. It was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results. A 'star system' has been developed in which a study is judged on three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively. The goal of this project is to develop an instrument providing an easy and convenient tool for quality assessment of nonrandomised studies to be used in a systematic review.
17,590 citations
"Circulating markers of oxidative st..." refers methods in this paper
...…the large number of subjects included in the analyses, the exclusion of duplicate reports and the medium- to high-quality requirement for inclusion of studies in the meta-analysis as assessed by a modified Newcastle-Ottawa Quality Assessment Scale for case–control studies (Wells et al., 2000)....
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...Studies reporting circulating markers of oxidative stress in women with PCOS and controls and published up to June 2012 were identified and analysed....
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...The studies included for the meta-analysis were appraised for their methodological quality according to a modification of the Newcastle-Ottawa Quality Assessment Scale for case–control studies (Wells et al., 2000), as presented in Table I....
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TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.
12,240 citations
"Circulating markers of oxidative st..." refers background in this paper
...Protective physiological mechanisms against oxidant species involve preventative and repair mechanisms, physical defences and antioxidant defences (Valko et al., 2007)....
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...But when present in excess, oxidants may damage DNA, cellular lipids and proteins, interfering with their normal function (Valko et al., 2007)....
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TL;DR: Since the 1990 NIH-sponsored conference on polycystic ovary syndrome, it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria.
8,217 citations