María Insenser

Bio: María Insenser is an academic researcher from University of Alcalá. The author has contributed to research in topics: Polycystic ovary & Adipose tissue. The author has an hindex of 19, co-authored 38 publications receiving 1346 citations. Previous affiliations of María Insenser include Carlos III Health Institute & Complutense University of Madrid.

Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis

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.

Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity

Abstract: Context Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function. Objective To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found. Design Cross-sectional study. Setting Academic hospital. Participants We recruited 15 women with PCOS, 16 nonhyperandrogenic control women, and 15 control men. Participants were classified as nonobese (<30 kg/m2) or obese (≥30 kg/m2) according to their body mass index. Interventions Standardization of diet for 3 consecutive days (at least 300 g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test. Main Outcome Measures Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S ribosomal DNA amplicons in a MiSeq platform (Illumina). Results α Bacterial diversity was reduced in women compared with men, and β diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catenibacterium and Kandleria genera. When all participants as a whole were considered, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels. Conclusions The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations, and obesity, presenting with specific abnormalities in women with PCOS.

Effects of Polycystic Ovary Syndrome (PCOS), Sex Hormones, and Obesity on Circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 Expression

Abstract: Context: MicroRNAs (miRNAs) are small, noncoding RNA sequences that negatively regulate gene expression at the post-transcriptional level. miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 have been associated with metabolic disorders such as obesity and diabetes, which are also associated with polycystic ovary syndrome (PCOS). Objective: We aimed to evaluate the effects of sex, sex hormones, and PCOS and their interactions with obesity on the expression in the circulation of these miRNAs. Design: This was a case-control study. Settings: The setting was an academic hospital. Participants: We included 12 control women, 12 patients with PCOS, and 12 men selected as to have similar body mass index (BMI) and age. Six subjects per group had normal weight (BMI < 25 kg/m2), and six subjects per group were obese (BMI ≥ 30 kg/m2). Interventions: Blood samples were collected early in the morning after a 12-hour fast. Main Outcome Measures: We measured whole blood expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-...

Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS

Abstract: BACKGROUND: Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity. METHODS: We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity. RESULTS: Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased α-tocopherol and cholesterol concentrations irrespective of obesity. CONCLUSIONS: Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder.

Diagnostic criteria for polycystic ovary syndrome

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.

Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment

Abstract: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in premenopausal women. Heterogeneous by nature, PCOS is defined by a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. The aetiology of this syndrome remains largely unknown, but mounting evidence suggests that PCOS might be a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors. PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders and cardiovascular risk factors. The diagnosis and treatment of PCOS are not complicated, requiring only the judicious application of a few well-standardized diagnostic methods and appropriate therapeutic approaches addressing hyperandrogenism, the consequences of ovarian dysfunction and the associated metabolic disorders. This article aims to provide a balanced review of the latest advances and current limitations in our knowledge about PCOS while also providing a few clear and simple principles, based on current evidence-based clinical guidelines, for the proper diagnosis and long-term clinical management of women with PCOS.

Clinical Relevance of Biomarkers of Oxidative Stress

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...

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

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.

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

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.