Assessment of baby disposable diapers application for urine collection and determination of phthalate metabolites.

The baby disposable diapers were investigated as a sampling material for urine collection and validated for the evaluation of the exposure of children to xenobiotics. Phthalate metabolites detected in urine samples were chosen as proof-of-concept analytes. For the determination of phthalate metabolites in children's urine samples, high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used. Two sampling approaches were compared, namely sterile containers and baby disposable diapers. Thirty urine samples from infants and toddlers were analyzed by both methods in parallel and the results were compared. It was found that for diaper sampling, lower concentrations of the metabolites were observed, however, the general distribution for particular metabolites remains the same for both methods. For most of the metabolites high determination coefficients were obtained, namely 0.9929 for MEHHP, 0.9836 for MMP, 0.9796 for MECPP, and 0.9784 for 2-cx-MMHP. For MEOHP the determination correlation coefficient was 0.9154, while for MBP was - 0.7771 and MEHP was - 0.5228. In general, for diaper sampling an underestimation for 2-cx-MMHP and MEOHP was observed, while for MMP diaper-based approach provides overestimation. However, the proposed procedure confirms the possibility of using baby disposable diapers as a material for the collection of urine samples for biomonitoring purposes and fast screening of phthalates exposure.

Environmental exposure to nonylphenol and cancer progression Risk-A systematic review.

Environmental exposure to nonylphenol (NP) can adversely affect human and wildlife health. A systematic review was conducted to evaluate the relationship between environmental NP exposure and cancer progression risk. Literature surveys were conducted within several international databases using appropriate keywords. A comprehensive search yielded 58 eligible studies involving a wide range of adverse effects, exposure assessment methods, study designs, and experimental models. Most studies reported that NP strongly induced breast cancer progression in intended experiments. Positive associations between NP exposure and ovarian, uterine, pituitary, and testicular cancers were also reported. Although some studies reported no relation between environmental NP exposure and tumour and/or cancer progression, NP (a known endocrine disrupting chemical) induced action mechanisms in multiple experimental models and may interfere with/hyper-activate oestrogen signalling. Secretion of oestrogen and development of reproductive tissues like breasts, uteruses, and ovaries showed strong associations with possible neoplasia (i.e., uncontrolled development of tumours and/or malignant cancers). Findings of this study are important for informing policymakers to pass legislation limiting the use of environmental contaminants such as NP before all adverse effects of exposure have been determined.

Metabolomic Insight into Polycystic Ovary Syndrome-An Overview.

Searching for the mechanisms of the polycystic ovary syndrome (PCOS) pathophysiology has become a crucial aspect of research performed in the last decades. However, the pathogenesis of this complex and heterogeneous endocrinopathy remains unknown. Thus, there is a need to investigate the metabolic pathways, which could be involved in the pathophysiology of PCOS and to find the metabolic markers of this disorder. The application of metabolomics gives a promising insight into the research on PCOS. It is a valuable and rapidly expanding tool, enabling the discovery of novel metabolites, which may be the potential biomarkers of several metabolic and endocrine disorders. The utilization of this approach could also improve the process of diagnosis and therefore, make treatment more effective. This review article aims to summarize actual and meaningful metabolomic studies in PCOS and point to the potential biomarkers detected in serum, urine, and follicular fluid of the affected women.

Genes responsible for proliferation, differentiation, and junction adhesion are significantly up-regulated in human ovarian granulosa cells during a long-term primary in vitro culture.

The human ovarian granulosa cells (GCs) surround the oocyte and form the proper architecture of the ovarian follicle. The ability of GCs to proliferate and differentiate in the conditions of in vitro culture has been proven. However, there is still a large field for extensive investigation of molecular basics, as well as marker genes, responsible for these processes. This study aimed to find the new marker genes, encoding proteins that regulate human GCs in vitro capability for proliferation and differentiation during long-term primary culture. The human follicular GCs were collected from hyper-stimulated ovarian follicles during IVF procedures and transferred to a long-term in vitro culture. The culture lasted for 30 days, with RNA samples isolated at days 1, 7, 15, 30. Transcriptomic analysis was then performed with the use of Affymetrix microarray. Obtained results were then subjected to bioinformatical evaluation and sorting. After subjecting the datasets to KEGG analysis, three differentially expressed ontology groups "cell differentiation" (GO:0030154), "cell proliferation" (GO:0008283) and "cell-cell junction organization" (GO:0045216) were chosen for further investigation. All three of those ontology groups are involved in human GCs' in vitro lifespan, proliferation potential, and survival capability. Changes in expression of genes of interest belonging to the chosen GOs were validated with the use of RT-qPCR. In this manuscript, we suggest that VCL, PARVA, FZD2, NCS1, and COL5A1 may be recognized as new markers of GC in vitro differentiation, while KAT2B may be a new marker of their proliferation. Additionally, SKI, GLI2, FERMT2, and CDH2 could also be involved in GC in vitro proliferation and differentiation processes. We demonstrated that, in long-term in vitro culture, GCs exhibit markers that suggest their ability to differentiate into different cells types. Therefore, the higher expression profile of these genes may also be associated with the induction of cellular differentiation processes that take place beyond the long-term primary in vitro culture.

Endocrine disrupting chemicals (EDCs) and female cancer: Informing the patients.

Breast and uterine cancer are the most frequent female gender related neoplasms whose growth is mostly estrogen dependent. Therefore, any EDC exhibiting estrogenic effects may increase the risk of these two malignancies. This review focuses on the potential role of EDCs with estrogenic potential on the risk of breast and uterine neoplasms but also points to the possible role of the exposure to EDCs in the pathogenesis of ovarian and cervical cancer. It also underlines the necessity of informing the public about the presence of EDCs in common consumer products, their detrimental health effects and methods of reducing the exposure risk.

Health risk of exposure to Bisphenol A (BPA).

Bisphenol A (BPA) belongs to chemicals that are produced in large quantities worldwide. It is commonly used as monomer in polycarbonate synthesis, plasticizer in the production of epoxy resins, as well as an additive for the elimination of surfeit of hydrochloric acid during the polyvinyl chloride (PVC) production. BPA is not only used in the production of plastics intended to a direct contact with food, including plastic packaging and kitchenware, but also in inner coatings of cans and jar caps. There are various routes of human exposure to this substance such as oral, by inhalation and transdermal. The main sources of exposure to BPA include food packaging and dust, dental materials, healthcare equipment, thermal paper, toys and articles for children and infants. BPA is metabolized in the liver to form bisphenol A glucuronide and mostly in this form is excreted with urine. Due to its phenolic structure BPA has been shown to interact with estrogen receptors and to act as agonist or antagonist via estrogen receptor (ER) dependent signalling pathways. Therefore, BPA has been shown to play a role in the pathogenesis of several endocrine disorders including female and male infertility, precocious puberty, hormone dependent tumours such as breast and prostate cancer and several metabolic disorders including polycystic ovary syndrome (PCOS). Because of the constant, daily exposure and its tendency to bio-accumulation, BPA seems to require special attention such as biomonitoring. This observation should include clinical tests of BPA concentration in the urine, which is not only one of the best methods of evaluation of the exposure to this compound, but also the dependence of the daily intake of BPA and the risk of some endocrine disorders.

Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is the most common and the most heterogeneous endocrine disorder in premenopausal women. Apart from signs of hyperandrogenism such as acne, hirsutism and hair loss, women with PCOS usually present with menstrual irregularities and fertility problems.Additionally, they are often characterized by impaired glucose tolerance, which usually leads to the development of type 2 diabetes mellitus (T2DM). This review article describes current and novel approach to the pathomechanisms of PCOS and the potential role of an endocrine disrupting chemical ("endocrine disruptor" - ED) - bisphenol A (BPA), which is commonly used as a plasticizer and due to its molecular structure can interact with estrogen receptors (ERs). Recent observations point to the higher levels of BPA in biological fluids of women with PCOS and its role in the pathogenesis of hyperandrogenism and hyperinsulinemia. It seems that mother's exposure to BPA during pregnancy may also lead to the development of PCOS in the female offspring.

Bisphenol A analogues and metabolic syndrome in women with polycystic ovary syndrome.

Bisphenols (BPs) have become a chemical group of special interest due to their ability to interfere with the endocrine system and their ubiquitous presence in the environment. As some of them possess mild estrogenic and anti-androgenic effects, they might be associated with the diagnosis of polycystic ovary syndrome (PCOS). Acting on multiple tissues, BPs exposure may lead to metabolic derangements characteristic for metabolic syndrome (MetS). Therefore, the aim of this study was to determine the potential relationship between exposure to some BPA analogues and features of the MetS in women with PCOS. Serum BPE, BPC, BPG, BPM, BPP, BPZ, BPFL, and BPBP concentrations did not differ significantly between the PCOS (n = 135) and the control subjects (n = 104). However, women whose serum BPM and BPP concentrations were in the highest tertile were more likely to be diagnosed with PCOS (adjusted OR; [95%CI] 0.43; [0.20; 0.89], P < 0.001 and 0.56; [0.27; 0.96], P = 0.049, consequently). Serum concentrations of BPs were not associated with the MetS diagnosis in the PCOS group. There was a negative correlation between the concentrations of serum BPBP and total serum cholesterol (r = - 0.153; P = 0.019), BPE and serum testosterone (r = - 0.160; P = 0.014) as well as BPC and HDL-cholesterol (r = - 0.138; P = 0.036). There was a positive correlation between the concentrations of BPP and serum triglycerides (r = 0.138; P = 0.036). Our results point to the potential association between exposure to BPM, BPP, and the diagnosis of PCOS, along with the impact of BPBP, BPE, BPC, and BPP on the metabolic features of the MetS.

Determination of urinary androgens in women with polycystic ovary syndrome using LC-QqQ/MS and the application of thin film solid-phase microextraction (TF-SPME).

Hyperandrogenism is one of the most pronounced symptoms of Polycystic Ovary Syndrome (PCOS) and seems to play a key role in the pathogenesis of this complex disorder. Nevertheless, there is still a lack of consistent results regarding common steroid predictors of PCOS. Therefore, a liquid chromatography tandem mass spectrometry (HPLC-QqQ/MS) method was developed and validated to determine the concentrations of four classic androgens: androstenedione (An-dione), testosterone (T), 5α-dihydrotestosterone (DHT) and androsterone (An) in urine samples obtained from women with PCOS and healthy controls. The limits of detection were between 0.04 and 0.09 ng/mL, while the limits of quantification ranged from 0.1 to 0.3 ng/mL respectively. As a pre-treatment procedure prior to analysis, hydrolysis using ß-glucuronidase and thin film solid-phase microextraction (TF-SPME) was applied. The methodology was employed to perform targeted metabolomics of urinary steroids in women with PCOS and healthy controls. All measured androgens: An-dione (p < 0.0001), T (p = 0.0001), DHT (p < 0.0001) and An (p = 0.0002) showed significantly higher concentrations in the urine of women with PCOS. The largest difference in the mean concentration was found for DHT, which was 2.8 times higher in the PCOS group (13.9 ± 14.1 ng/mg creatinine) in comparison to healthy controls (4.9 ± 3.4 ng/mg creatinine). The results of receiver operating characteristic curve indicated that determination of the panel of three urinary androgens: T+DHT+An-dione with, under the study assumptions, was the best predictor of PCOS diagnosis (AUC of ROC curve = 0.91 (95 % CI: 0.8212-0.9905). The application of an LC-MS/MS-based analysis, together with highly sensitive extraction techniques like TF-SPME, is a suitable approach to perform fast assays and obtain reliable results - crucial in the search for valuable and significant steroids predictors of PCOS.

Relationship between serum transforming growth factor ß 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents.

The aim of this study was to evaluate the relationship between serum transforming growth factor ß 1 (TGF- ß 1) concentrations and the duration of type 1 diabetes mellitus (T1DM) in children and adolescents. One hundred and sixteen patients with T1DM and 19 healthy controls were examined. Serum TGF- ß 1 concentrations were measured using the cytometric bead array (CBA). A positive association between the time of diabetes duration and higher serum TGF- ß 1 concentrations was observed. Similarly, the prevalence of microvascular complications, such as retinopathy and nephropathy, increased with the duration of diabetes. Logistic regression analysis showed that serum TGF- ß 1 concentrations and the duration of the disease are independent risk factors of microangiopathy development. Higher serum TGF- ß 1 concentrations were associated with a significant risk of microangiopathy development after 10 years of T1DM duration. In the successive years of the disease, the effect was even stronger. The results of our study indicate that serum TGF- ß 1 concentrations are one of the factors that may have an impact on the progression of vascular complications in children and adolescents with T1DM.

Specific Alteration of Branched-Chain Amino Acid Profile in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive age women; it is a complex health issue with numerous comorbidities. Attention has recently been drawn to amino acids as they are molecules essential to maintain homeostasis. The aim of the study was to investigate the branch chain amino acid (BCAA) profile in women with PCOS. A total of 326 women, 208 diagnosed with PCOS and 118 healthy controls, participated in the study; all the patients were between 18 and 40 years old. Anthropometrical, biochemical and hormonal parameters were assessed. Gas-liquid chromatography combined with tandem mass spectrometry was used to investigate BCAA levels. Statistical analysis showed significantly higher plasma levels of BCAAs (540.59 ± 97.23 nmol/mL vs. 501.09 ± 85.33 nmol/mL; p < 0.001) in women with PCOS. Significant correlations (p < 0.05) were found between BCAA and BMI, HOMA-IR, waist circumference and total testosterone levels. In the analysis of individuals with abdominal obesity, there were significant differences between PCOS and controls in BCAA (558.13 ± 100.51 vs. 514.22 ± 79.76 nmol/mL) and the concentrations of all the analyzed amino acids were higher in the PCOS patients. Hyperandrogenemia in PCOS patients was associated with significantly higher leucine, isoleucine and total BCAA levels. The increase of BCAA levels among PCOS patients in comparison to healthy controls might be an early sign of metabolic alteration and a predictive factor for other disturbances.

Alteration of Branched-Chain and Aromatic Amino Acid Profile as a Novel Approach in Studying Polycystic Ovary Syndrome Pathogenesis.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive-age women and predisposes them to the development of metabolic disturbances. Recent research has shown that several metabolic factors may play a role in PCOS pathogenesis, and it has been suggested that an alteration in the amino acid profile might be a predictive sign of metabolic disorders. Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are concepts that have attracted scientific attention; however, a universal definition has not been established yet for these terms. Already existing definitions of MHO involve the coexistence of obesity with the absence or minimal presence of other metabolic syndrome parameters. A group of 326 women, 209 diagnosed with PCOS and 117 healthy individuals, participated in this study. Multiple parameters were assessed, including anthropometrical, biochemical, and hormonal ones, and gas-liquid chromatography, combined with tandem mass spectrometry, was used to investigate the amino acid profile. Statistical analysis revealed noticeably higher levels of all aromatic amino acids in PCOS women compared to the control group: phenylalanine 47.37 ± 7.0 vs. 45.4 ± 6.09 nmol/mL (p = 0.01), tyrosine 61.69 ± 9.56 vs. 58.08 ± 8.89 nmol/mL (p < 0.01), and tryptophan 53.66 ± 11.42 vs. 49.81 ± 11.18 nmol/mL (p < 0.01); however, there was no significant difference in the "tryptophan ratio" between the PCOS and control group (p = 0.88). A comparison of MHO and MUO PCOS women revealed that LAP, leucine, and isoleucine concentrations were significantly higher among the MUO subgroup: respectively, 101.98 ± 34.74 vs. 55.80 ± 24.33 (p < 0.001); 153.26 ± 22.26 vs. 137.25 ± 25.76 nmol/mL (p = 0.04); and 92.92 ± 16.09 vs. 82.60 ± 18.70 nmol/mL (p = 0.02). No significant differences in BMI, fasting glucose, and HOMA-IR between MHO and MUO were found: respectively, 35.0 ± 4.8 vs. 36.1 ± 4.6 kg/m2 (p = 0.59); 88.0 ± 6.0 vs. 87.73 ± 6.28 mg/dL (p = 0.67); and 3.36 ± 1.70 vs. 4.17 ± 1.77 (p = 0.1). The identification of altered amino acid profiles in PCOS holds potential clinical implications. Amino acids may serve as biomarkers for diagnosing and monitoring the metabolic status of individuals with PCOS. The alteration of BCAAs and AAAs may be involved in PCOS pathogenesis, but the underlying mechanism should be further investigated.

Searching for the primary metabolic alterations of polycystic ovary syndrome by application of the untargeted metabolomics approach.

Despite a large number of studies, the pathogenesis of polycystic ovary syndrome (PCOS) still remains unexplained. In light of ambiguous observations reported in metabolomics, there is a need to carry out studies focusing on confirming the discriminating power of the proposed metabolomics biomarkers. Our research aimed to perform a validation study of metabolites detected in our previous study from serum samples, on the new set of samples obtained from PCOS women and healthy controls to confirm previously selected compounds. Additionally, the second biological matrix - urine - was used to get a more comprehensive insight into metabolic alterations. We applied two analytical techniques - gas chromatography and liquid chromatography coupled with mass spectrometry to analyze both serum and urine samples obtained from 35 PCOS patients and 35 healthy women. Thank to our approach, we identified and described a comprehensive set of metabolites altered in PCOS patients. Results of our study indicate increased steroid hormone synthesis, alteration in sphingo- and phospholipids metabolism, and disturbed fatty acids metabolism. Moreover, the citric acid cycle, γ-glutamyl cycle, vitamin B metabolism, and a few primary amino acids like tryptophan, phenylalanine, histidine, and alanine are altered.

Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.

Serum bisphenol A analogues in women diagnosed with the polycystic ovary syndrome - is there an association?

Due to the endocrine disrupting effects of bisphenol A (BPA) several governmental authorities have banned its use and the manufacturers had to find alternative substances with similar chemical properties. This led to the increase in the use of so-called BPA analogues, which however also turn out to possess mild estrogenic and ani-androgenic properties and thus, may cause fertility problems and sex-hormone dependent endocrinopathies. The aim of this study was to evaluate the potential association between the exposure to BPA and its two analogues: BPS and BPF, with the diagnosis of the polycystic ovary syndrome (PCOS), which remains the most common female endocrinopathy. Serum concentrations of BPA, BPS and BPF were measured using high performance liquid chromatography method with tandem mass spectrometry (HPLC-MS/MS) among 199 women with PCOS and 158 control subjects. In women with PCOS serum BPS concentrations were significantly higher compared to the control subjects (geometric mean [95% CI]: 0.14 ng/mL [0.10; 1.17] vs. 0.08 ng/mL [0.06; 0.09], P = 0.023). Serum BPA and BPF concentrations did not differ between the studied groups. There was however a negative correlation between serum BPA and HOMA-IR (r = - 0.233, P = 0.001) and TST (r = - 0.203, P = 0.006) in women with PCOS. No correlations were found between the serum BPs and other metabolic parameters such as serum lipids, insulin, DHEA-S, androstenedione and FAI. When studying the association between serum BPA analogues and PCOS it turned out that women whose serum BPS concentrations were in the first tertile were more likely to be diagnosed with this endocrinopathy (OR [95% CI]: 1.21 [1.04; 3.46], P = 0.017). This association was also statistically significant when adjusted for age, education, BMI, smoking, income, and alcohol consumption (adjusted OR [95% CI]: 1.12 [1.03; 3.71], P = 0.029). These results point to the potential association between the exposure to BPS and the diagnosis of PCOS. The role of BPA is not clear and warrants further studies.

Recommendations of the Polish Sexological Society on medical care in transgender adults - position statement of the expert panel. / Zalecenia Polskiego Towarzystwa Seksuologicznego dotyczace opieki nad zdrowiem doroslych osób transplciowych ­ stanowisko panelu ekspertów.

Attempts at unifying the diagnostic and therapeutic procedures for transgender individuals experiencing gender dysphoria were first undertaken in Poland in the 1980s. Since then, there has been a change in the perception of transgenderism, almost paradigmatic, expressed in subsequent editions of the diagnostic systems (DSM, ICD), which is also associated with the fundamental changes in the principles of conducting trans-specific healthcare. This triggered the need to formulate recommendations for specialists practicing in Poland, which would at least partly reflect the evolution of views and guidelines on clinical care in transgender adults seeking help due to gender dysphoria.

Exposure to Bisphenol A Analogs and the Thyroid Function and Volume in Women of Reproductive Age-Cross-Sectional Study.

Bisphenols (BPs) are commonly known plastifiers that are widely used in industry. The knowledge about the impact of BPs on thyroid function is scarce. Proper thyroid functioning is especially important for women of reproductive age, as hypothyroidism affects fertility, pregnancy outcomes and the offspring. There are no studies analyzing the influence of BPs on thyroid function and volume in non-pregnant young women. The aim of this cross-sectional study was to evaluate the relationship between bisphenol A and its 10 analogs (BPS, BPC, BPE, BPF, BPG, BPM, BPP, BPZ, BPFL, and BPBP) on thyroid function and volume in women of reproductive age. Inclusion criteria were: female sex, age 18-40 years. Exclusion criteria were history of any thyroid disease, pharmacotherapy influencing thyroid function, pregnancy or puerperium, and diagnosis of autoimmune thyroid disease during this study. Venous blood was drawn for measurement of thyrotropin (TSH), free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies, BPs. Urine samples were analyzed for: ioduria and BPs. Ultrasound examination of thyroid gland was performed. One hundred eighty participants were included into the study. A negative correlation was found between urine BPC and the thyroid volume (R = -0.258; p = 0.0005). Patients with detected urine BPC presented smaller thyroid glands than those with not-detected urine BPC (p = 0.0008). A positive correlation was found between TSH and urine BPC (R = 0.228; p = 0.002). Patients with detected urine BPC presented higher concentrations of TSH versus those with not-detected urine BPC (p = 0.003). There were no relationships between any of serum BPs as well as the other urine BPs and thyroid function and its volume. The only BP that demonstrated the relationship between thyroid function and its volume was BPC, probably because of its chemical structure that most resembles thyroxine. Exposure to this BP may result in the development of hypothyroidism that could have a negative impact on pregnancy and the offspring.

Inflammatory response of coronary artery disease postmenopausal women is associated with the IVS1-397T > C estrogen receptor alpha polymorphism.

We analyzed the relationship between the IVS1-397T > C polymorphism of estrogen receptor alpha gene and inflammatory response of eighty postmenopausal women with an established coronary artery disease (CAD). We found that the IVS1-397T allele carriers exhibited an enhanced inflammatory response in vivo and in vitro. These patients had a higher number of total monocytes and their CD14(+)CD16(+) inflammatory subset in relation to CC homozygotes. The CT and TT women's LPS-stimulated whole blood cell cultures produced more IL6 and TNFalpha than did the cultures of CC women. Moreover, significantly more of the T allele patients had major post-coronary artery bypass grafting complications and less of them experienced subjective angina pectoris improvement. Summarizing, the IVS1-397T > C polymorphism allows us to identify a group of postmenopausal women with the strong inflammatory response which is associated with a higher incidence of the major post-CABG adverse cardiovascular complications.

[Recomendations on non-pharmacological interventions in women with PCOS to reduce body weight and improve metabolic disorders [Zalecenia dotyczace postepowania niefarmakologicznego u kobiet z PCOS celem zmniejszenia masy ciala i poprawy zaburzen metabolicznych]].

Women with PCOS are characterised by ovarian hyperandrogenism, which, apart from fertility problems, hirsutism, acne, and androgenic alopecia, also leads to the development of central (android) obesity and its adverse metabolic consequences. Additionally, women with PCOS have intrinsic insulin resistance (IR) with its consequent hyperinsulinaemia, which leads to the development of atherosclerosis, arterial hypertension, and type 2 diabetes mellitus (T2DM), which give rise to cardiovascular disease (CVD), being the main cause of death among women. Although there are several publications on the topic of life-style changes in women with PCOS to normalise body weight and thus to reduce the adverse metabolic consequences of obesity, such as T2DM and CVD, the number of randomised studies that would enable the formation of strong recommendations is very limited. Nevertheless, taking into consideration the pathophysiology, any intervention implementing healthy dietary habits leading to the reduction of body weigh should be the core of non-pharmacological treatment in women with PCOS. The aim of the given recommendations herein is to point out and systemise the interventions on lifestyle change in women with PCOS as well as to form a practical guideline for the health care specialists, dieticians, and mental-therapists (psychologist) who take care of women with this syndrome.

Identification of the metabolic fingerprints in women with polycystic ovary syndrome using the multiplatform metabolomics technique.

In addition to chronic anovulation and clinical signs of hyperandrogenism women with polycystic ovary syndrome (PCOS) are insulin resistant and therefore, develop central obesity with its long term consequences such as dyslipidaemia, hypertension, atherosclerosis and type 2 diabetes mellitus (T2DM), which all lead to the development of cardiovascular disease (CVD). Due to the polysymptomatic nature of this syndrome and lack of consensus on its diagnostic criteria there is a strong need of finding a reliable biochemical or molecular marker, which would facilitate making the accurate diagnosis of PCOS. Therefore, the aim of our study was to perform a metabolomics analysis with the use of two complementary techniques: gas chromatography and liquid chromatography coupled with mass spectrometry, of the serum samples from women with PCOS (n = 30) and to compare them with healthy age and BMI matched controls (n = 30). Obtained results were subjected to one-dimensional statistical analysis (student's t-test or its non-parametric equivalent U Mann-Whitney test) and multivariate statistical analysis (the principal component analysis [PCA], variable importance into projection [VIP] and selectivity ratio [SR]). The results of our study showed that women with PCOS are characterised by metabolic disorders of the amino acids, carbohydrates, steroid hormones, lipids and purines. Compared to control subjects, women with PCOS had increased serum levels of phospholipids, aromatic amino acids, organic acids, hormones and sphinganine and decreased total cholesterol. Among the identified compounds, total cholesterol, phenylalanine and dehydroepiandrosterone sulfate, uric and lactic acid were the compounds with the strongest discriminating power.