Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

STUDY QUESTION: Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER: This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY: Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION: A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE: We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS: Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Elevation of markers of endotoxemia in women with polycystic ovary syndrome.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with an elevation of markers of endotoxemia? SUMMARY ANSWER: In women with PCOS serum levels of lipopolysaccharides (LPS), the LPS to high-density lipoprotein (HDL) ratio and LPS-binding protein (LBP) are significantly greater than those of normal control subjects. WHAT IS KNOWN ALREADY: Mononuclear cells from women with PCOS respond excessively to LPS by releasing pro-inflammatory cytokines. In rat ovarian theca-interstitial cell cultures LPS stimulates androgen production. STUDY DESIGN, SIZE, DURATION: Cross-sectional study comparing markers of endotoxemia in women with PCOS (n = 62), healthy ovulatory women with polycystic ovary morphology (PCOM, n = 39) and a control group of healthy ovulatory women without PCOM [normal (NL), n = 43]. PARTICIPANTS/MATERIALS, SETTING, METHODS: LPS was measured using a chromogenic assay. LBP was measured by ELISA. Total cholesterol and lipids were measured using a homogeneous enzyme colorimetric method. Androgens, gonadotrophins, prolactin, insulin, high-sensitivity C-reactive protein (hs-CRP) and sex hormone-binding globulin were determined by electrochemiluminescence assays. Glucose was measured using an enzymatic reference method with hexokinase. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS, when compared with NL subjects, had a significantly higher mean LPS (P = 0.045), LPS/HDL ratio (P = 0.007) and LBP (P = 0.01). Women with PCOM had intermediate levels of markers of endotoxemia. Comparison among all groups revealed that markers of endotoxemia correlated positively with testosterone level, ovarian volume, number of antral follicles and hirsutism score, but negatively with the number of spontaneous menses per year. In multiple regression analysis, all measures of endotoxemia correlated independently and positively with hs-CRP and with ovarian volume. LIMITATIONS, REASONS FOR CAUTION: This cross-sectional study reveals that markers of endotoxemia are associated with several clinical features observed in women with PCOS. However, responsible mechanisms and causation remain unknown. Steroid quantification was carried out by electrochemiluminescence assays and not by the current gold standard: liquid chromatography-mass spectrometry. Hence, the relationship of endotoxemia with features of PCOS and the extent to which endotoxemia contributes to reproductive and metabolic dysfunction warrants further investigation. WIDER IMPLICATIONS OF THE FINDINGS: This study reveals the novel observation that markers of endotoxemia are elevated in young and otherwise healthy women with PCOS without significant metabolic dysfunction. Moreover, the association of clinical and endocrine markers of PCOS with those of endotoxemia may represent a pathophysiologic link to reproductive dysfunction as well as metabolic and long-term cardiovascular risks associated with this disorder. STUDY FUNDING/COMPETING INTEREST(S): Intramural funding from Poznan University of Medical Sciences. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Determinants of emotional problems and mood disorders in women with polycystic ovary syndrome.

OBJECTIVES: The aim of the study was to assess the prevalence and severity of emotional problems among Polish women with polycystic ovary syndrome (PCOS) and seek factors which increase the risk of their occurrence. MATERIAL AND METHODS: The study group consisted of 82 women (aged 18-48), who were diagnosed with PCOS based on the Rotterdam criteria. During hospitalization, the patients completed a number of questionnaires, providing their sociodemographic data and information concerning the inconvenience of disease-associated symptoms. The question-naires included the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and Multidimensional Self-Esteem Inventory (MSEI). Data obtained during medical examinations (blood tests, transvaginal ultrasound, height and body mass measurements) were analyzed. RESULTS: Out of 82 women, the results detected risk for depression in 42 (51.22%), mild depressive disorders in 32, moderate disorders in 8, and severe disorder in 2 patients. No statistically significant correlation between BDI or state anxiety and the level of the analyzed hormones, insulin resistance, or infertility treatment, was found. General self-esteem, trait anxi-ety, and marital status were associated with the occurrence of depression symptoms. BMI was associated with the level of state anxiety during hospitalization. CONCLUSIONS: Women with PCOS are at risk for mood and anxiety disorders. Disease-related somatic factors are not directly associated with the risk for disorder occurrence. However, severity of depression symptoms has been shown to be influenced by permanent psychological characteristics of the studied women, i.e. self-esteem, trait anxiety, and life situation (marital status). Therefore, it is recommended to include interviews about patient life situation and screening questionnaires for assessing depression into the diagnostic procedures in PCOS patients. Patients should be referred for a psychological or psychiatric consultation, if needed.

[Occurrence of Chlamydia trachomatis infections in infertile women in Poland]. / Wystepowanie zakaien Chlamydia trachomatis u kobiet z nieplodnoscia w Polsce.

INTRODUCTION: Chiamydia trachomatis represents a causal factor of sexually transmitted infections (STI), the course of which is frequently asymptomatic. Chronic and relapsing infections with Chlamydia trachomatis may result in a disturbed function of oviducts, resulting in infertility. OBJECTIVES: The aim of the study was to evaluate the relationship between manifestations of asymptomatic infections with Chlamydia trachomatis and infertility among Polish women. MATERIAL AND METHODS: The study was conducted between 2010-2013 on 543 women in two groups. Group 1 included 190 patients (aged 23-39 years), in whom control tests were performed before planned pregnancy Group 2 included 353 patients (aged 23-39 years), suffering from infertility (no pregnancy after 12 months of regular sexual intercourse). The study included all women presenting with infertility A smear was taken from the cervical canal and DNA of C. trachomatis was isolated and identified using nested-PCR. In the statistical analysis the Fisher's exact test was applied. RESULTS: Infection with C. trachomatis was detected in 18 (9.47%) controls (group 1) but as many as 81 (22.95%) patients with infertility (group 2). The obtained results were significantly different (p<0.0001) between the investigated groups. CONCLUSIONS: (1) The study indicates that chronic infection with C. trachomatis may represent a significant factor resulting in infertility of women. (2) A test for Chlamydia trachomatis infection should be routinely performed in every couple with diagnosed infertility and always before a scheduled in vitro procedure.

Decreased large-artery stiffness in midluteal phase of the menstrual cycle in healthy women of reproductive age.

OBJECTIVES: Sex hormones are specific factors contributing to the regulation of cardiovascular system. Studies on the effects of hormonal fluctuations during the menstrual cycle on hemodynamics and arterial stiffness in young women are limited and provide conflicting results. AIM: The aim of the study was to assess arterial stiffness, peripheral/central blood (pBP and cBP) and pulse (pPP and cPP) pressures throughout the single, natural menstrual cycle (early follicular [EFP], late follicular [LFP] and midluteal [LP] phase). MATERIALS AND METHODS: Forty two healthy regularly menstruating women (28.6±5.1 yrs of age; BMI 22.0±3.5 kg/m2) were evaluated during EFP (Estradiol [E], FSH, LH, PRL, TSH, Testosterone [T], DHEAS, and SHBG), LFP (E, FSH, LH) and LP (Progesterone, E, FSH, LH). Transvaginal ultrasound was performed to confirm ovulatory cycle. Resting radial and aortic BP were assessed noninvasively and continuously using tonometric measurement of peripheral PP wave-PPW (Colin BMP7000, Japan) and on-line reconstruction of central PPW (Sphygmocor Mx, Australia) at EFP, LFP and LP. ANOVA and Friedman test were used in statistical analysis. RESULTS: There were no significant differences in systolic/diastolic BP and PP both at the periphery and at ascending aorta throughout the menstrual cycle. Comparable observations of no interphasal differences were noted for peripheral Augmentation Index (AI). Central AI and augmentation pressure (AP) were significantly lower in LP than in LFP (by 4%; p<0.05 and by 37%; p<0.05, respectively). CONCLUSIONS: We demonstrated significant differences in mechanical properties of large arteries at the midluteal phase of natural menstrual cycle. We conclude that sex hormones may play role in the regulation of arterial stiffness in the reproductive age women.

Bacterial Vaginosis (BV) and Vaginal Microbiome Disorders in Women Suffering from Polycystic Ovary Syndrome (PCOS).

Introduction: Polycystic ovary syndrome (PCOS) is a multifactorial, heterogeneous endocrine and metabolic disorder in women. Due to its association with the menstrual cycle and fertility disorders, the importance of this problem is emphasized especially in patients of reproductive age. Based on a number of analyses, the effect of PCOS on altering the diversity of the microbiome (e.g., intestinal or vaginal) is suggested. Vaginal dysbiosis can result in BV (bacterial vaginosis). The purpose of this study was to assess the prevalence of BV in patients with PCOS, as well as to determine the most reliable diagnostic factors. Material and Methods: Retrospective analysis of microbiological findings (2018-2022) of PCOS patients (n = 594) of reproductive age. The present analysis focused on the results of patients with PCOS (n = 380) and vaginal discharge with pH ≥ 4.4 and suspected BV. Biological material was a vaginal swab/vaginal secretion. The most commonly used routine methods for assessing BV were the Amsel analysis and the Nugent scoring system. Results: Patients with PCOS and vaginal fluid pH ≥ 4.4 and suspected BV (n = 380) accounted for 64% of all PCOS patients (n = 594). The relationship between pH and detection of "clue cells" showed significant dependency and increased with leukocytes. The pH measurement also showed dependency on high G. vaginalis counts. In addition, the elimination of lactic acid bacteria (LAB) in vaginal secretions was associated with an increase in the number of leukocytes with increasing pH values. A marked increase in G. vaginalis was found in more than half (56.8%) of PCOS women (n = 380) with suspected BV. No dependency was observed between the absence of LAB and the diagnosis of BV on a positive G. vaginalis culture. Of the n = 380 patients with PCOS, 191 (50%) had a Nugent score ≥ 7 positive for BV. No dependency was observed between the number of patients with Candida sp. in vaginal secretions and pH, BV (with clue cells), or elevated leukocyte levels. The LRM was adjusted and the statistical model represented by the following formula was obtained: log(p/(1 - p)) = -1.18 + 1.24 × Group4.6 + 1.08 × Group4.8 + 1.66 × Group5.4. Conclusions: Based on the present analysis, BV appears to be more common in patients with PCOS than in the non-PCOS population. Chronic inflammation in PCOS patients and abnormalities in the vaginal microbiome may predispose to the development of BV. In women with PCOS, BV may be one of the unrecognized causes of infertility or complications of pregnancy. Despite the potential link between PCOS and the development of BV, the extent to which this syndrome contributes to vaginal dysbiosis and reproductive complications requires further study.

The SPRi determination of cathepsin L and S in plasma and peritoneal fluid of women with endometriosis.

PURPOSE: Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis. MATERIAL AND METHODS: In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor. RESULTS: The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma. CONCLUSIONS: Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis.

Is the leptin/BMI ratio a reliable biomarker for endometriosis?

Background: The aim of this study was to analyze the concentration of leptin in peritoneal fluid and plasma and to assess their role as potential biomarkers in the diagnosis of endometriosis. Materials & methods: Leptin adjusted for BMI (leptin/BMI ratio) was measured using surface plasmon resonance imaging (SPRI) biosensors. Patients with suspected endometriosis were included in the study. Plasma was collected from 70 cases, and peritoneal fluid from 67 cases. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group and a control group (patients without endometriosis). Results: Leptin/BMI ratio in plasma did not differ between women with endometriosis and the control group (0.7159 ± 0.259 vs 0.6992 ± 0.273, p= 0,7988). No significant differences were observed in peritoneal leptin/BMI ratio levels in patients with and without endometriosis (0.6206 ± 0.258 vs 0.6215 ± 0.264, p= 0,9896). Plasma and peritoneal leptin/BMI ratios were significantly lower in women with endometriosis - related primary infertility compared to women with endometriosis without primary infertility (0.640 ± 0.502 vs 0.878 ± 0.623, p < 0.05). The difference was observed in case of primary infertility, but not in terms of the secondary one. No significant differences were noted between leptin/BMI ratio in the proliferative phase and the secretory phase (0.716 ± 0.252 vs 0.697 ± 0.288, p= 0,7785). Conclusion: The results of present study do not support the relevance of leptin concentration determination as a biomarker of the endometriosis. Due to the limited number of samples in the tested group, further studies are needed to confirm its role.

Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies.

Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome. We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS). Sixty-two healthy, untreated women with PCOS (age 25.1 ± 3.6 years, BMI: 24.0 ± 4.7 kg/m(2)) were randomized to metformin (n = 24), simvastatin (n = 20) or metformin plus simvastatin (n = 18) for 3 months. Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end. At the baseline serum FABP4 correlated with obesity (BMI: r = 0.63, p < 0.001), insulin resistance (fasting insulin: r = 0.44, p = 0.0002; QUICKI: r = -0.30, p = 0.02; OGTT-insulin sensitivity index: r = -0.27, p = 0.04), dyslipidemia (HDL: r = -0.26, p = 0.03) and hyperandrogenemia (free-testosterone: r = 0.23, p = 0.03; SHBG: r = -0.28, p = 0.03); while RBP4 correlated with total-cholesterol (r = 0.33, p = 0.009). Multiple regression analysis indicated that t best predictors of serum FABP4 and RBP4 were BMI (ß = 1.02, p = 0.0003) and total cholesterol (ß = 2326, p = 0.01), respectively. Simvastatin, alone or with metformin did not affect serum FABP4 or RBP4. Serum FABP4 related to the obesity, insulin resistance and inflammation while RBP4 related to lipids. Insulin sensitizing and lipid lowering therapies did not affect FABP4 or RBP4 levels in PCOS.

Time Perspective as a Mediator of Depressive Symptoms in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by oligo- or anovulation, clinical and/or biochemical markers of hyperandrogenism, and polycystic ovaries, and it is associated with an increased prevalence of depression. Research conducted on psychiatric patients has shown correlations between depression and decreased cognitive function. The aim of this study was to examine the possible mediation of the time perspective (TP) in the development of depressive symptoms in patients with PCOS. METHODS: A study was conducted on 83 patients with PCOS and 65 healthy women. Standardized questionnaires were used to assess depressive symptoms (Beck Depression Inventory-BDI-II) and time perspective (Zimbardo Time Perspective Inventory-ZTPI). RESULTS: Our study revealed an indirect influence of depressive symptoms on PCOS through the positive future time perspective. In the logistic regression model, which included depression and a given time perspective as predictors of PCOS, only the future TP (ß = -0.004, p < 0.003, OR = 1.004, 95% CI [1.001, 1.008]) was significantly independently related to the occurrence of PCOS. CONCLUSIONS: Our result is another argument for the role of psychoeducation and appropriate communication with a patient from the risk group in a way that builds hope and allows to regain influence on life situation.

Plasma and Peritoneal Fluid Annexin A2 Levels in Patients with Endometriosis.

Introduction: Endometriosis is an inflammatory-related reproductive age disease characterized by the presence of endometrial cells outside the uterine cavity. Current laboratory practice does not provide specific markers for detecting and assessing the advancement of endometriosis in either plasma or peritoneal fluid. The severity of disease is assessed in stages from I to IV based on the results of laparoscopic inspection. The protein annexin A2 (ANXA2) has been reported to be associated with inflammatory processes. Aim of the Study: The study aimed to investigate and compare ANXA2 protein concentration using the ELISA method in plasma and peritoneal fluid in a group of women with endometriosis compared to controls. Materials and Methods: Biological material was collected during a multicenter, cross-sectional study, which was conducted at eight departments during elective laparoscopy from 53 women with and 40 women without endometriosis. Patients were divided by endometriosis stage and infertility status, and then compared with subgroups. Analysis included the Chi-square test for categorical variables, Mann-Whitney U-test and two-sided Wilcoxon rank-sum test for continuous variables. Results: Women with endometriosis had significantly elevated plasma ANXA2 levels compared to women without endometriosis (mean concentrations 28.69 vs 19.61 ng/L, p=0.01). Differences in peritoneal fluid ANXA2 levels were statistically insignificant (mean concentrations of 23.7 vs 22.97 ng/L, p=0.06). Plasma concentrations in patients with stage III and IV endometriosis were significantly higher compared to controls (mean concentrations of 24.19 vs 19.71 ng/L, p=0.03). No such differences were observed in plasma when comparing stages I-II vs III-IV, and stages I-II vs controls (mean concentrations of 33.82 vs 24.19 ng/L, p=0.72 and 33.82 vs 19.71 ng/L, p=0.12, respectively). Comparison of samples from patients with or without infertility, primary or secondary infertility, endometriosis with or without infertility, and non-endometriosis with or without infertility showed no significant differences in the plasma nor in the peritoneal fluid concentrations. Conclusion: ANXA2 is possibly involved in the pathogenesis of endometriosis, especially in advanced stages. Due to the limited group of tested samples, further studies are needed to confirm its role.

The Role of Individually Selected Diets in Obese Women with PCOS-A Review.

Polycystic ovarian syndrome (PCOS) is one of the most common heterogeneous endocrine and metabolic disorders in premenopausal women. It is a complex multifactorial disorder with strong epigenetic and environmental influences, including factors related to eating habits and lifestyle. There is a close relationship between obesity and PCOS. Weight gain and obesity are often clinical symptoms manifested by biochemical markers. Moreover, abdominal obesity in women with PCOS is involved in the development of inflammatory changes. A significant share of balanced therapies correcting the lifestyle of patients is suggested, e.g., with the implementation of appropriate diets to minimize exposure to inflammatory factors and prevent abnormal immune system stimulation. In the case of obese patients with PCOS, planning a diet program and supporting the motivation to change eating habits play an important role to lose weight and lower BMI. Probiotics/synbiotic supplementation may enhance weight loss during the diet program and additionally positively affect metabolic and inflammatory factors by improving the intestinal microbiome.

Cardiovascular Function in Different Phases of the Menstrual Cycle in Healthy Women of Reproductive Age.

Background: Sex hormones influence the cardiovascular (CV) function in women. However, it is uncertain whether their physiological variation related to the regular menstrual cycle affects the CV system. We studied changes in the hemodynamic profile and body's water content and their relation to sex hormone concentration in healthy women during the menstrual cycle. Material and methods: Forty-five adult women were examined during the early follicular, late follicular, and mid-luteal phases of the same menstrual cycle. The hemodynamic profile was estimated non-invasively by cardiac impedance while water content was estimated by total body impedance. Results were compared with repeated measures ANOVA with post-test, if applicable. Results: There were no significant changes in most hemodynamic and water content parameters between the menstrual cycle phases in healthy women. Left ventricular ejection time differed significantly among phases of the menstrual cycle, with shorter values in the mid-luteal phase (308.4 vs. 313.52 ms, p < 0.05) compared to the late follicular phase. However, the clinical relevance of such small differences is negligible. Conclusions: Changes in sex hormones during the physiological menstrual cycle appear to have no considerable effect on healthy women's hemodynamic function and water accumulation.

Ibuprofen Reduces Testosterone Level in Women With Polycystic Ovary Syndrome.

Context: Hyperandrogenism is a central feature of polycystic ovary syndrome (PCOS). In vitro studies have demonstrated that inflammatory stimuli promote whereas ibuprofen inhibits androgen production by ovarian theca-interstitial cells. Objective: This work aimed to determine the effects of nonselective inhibitor of cyclooxygenases COX-1 and COX-2 on testosterone levels. Methods: A prospective pilot study took place in an academic hospital of women with PCOS defined according to Rotterdam criteria (N = 20). Evaluations were taken at baseline and after 3 weeks of ibuprofen administration (400 mg twice a day or 400 mg 3 times a day, respectively, in women with weight < and ≥ 70 kg). The main outcome measure was total serum testosterone. Results: Ibuprofen administration was associated with a decline of total testosterone from 0.75 ±â€…0.06 ng/mL to 0.59 ±â€…0.05 ng/mL (P = .008). There was no statistically significant change in the levels of other relevant hormones including dehydroepiandrosterone sulfate, gonadotropins, and insulin. Multiple regression analysis identified the greatest decline of testosterone was independently predicted by baseline testosterone level (P = .004) and by baseline insulin sensitivity index (P = .03). Conclusion: Nonselective inhibition of COX-1 and COX-2 leads to selective reduction of testosterone consistent with direct inhibitory effect on ovarian steroidogenesis.

The Role of Cadherin 12 (CDH12) in the Peritoneal Fluid among Patients with Endometriosis and Endometriosis-Related Infertility.

Cadherin 12 (CDH 12) can play a role in the pathogenesis of endometriosis. The aim of this study was to compare the levels of cadherin 12 in the peritoneal fluid between women with and without endometriosis. This was a multicenter cross-sectional study. Eighty-two patients undergoing laparoscopic procedures were enrolled in the study. Cadherin 12 concentrations were determined using the enzyme-linked immunosorbent assay. The level of statistical significance was set at p < 0.05. No differences in cadherin 12 concentrations between patients with and without endometriosis were observed (p = 0.4). Subgroup analyses showed that CDH 12 concentrations were significantly higher in patients with infertility or primary infertility and endometriosis in comparison with patients without endometriosis and without infertility or primary infertility (p = 0.02) and also higher in patients with stage I or II endometriosis and infertility or primary infertility than in patients without endometriosis and infertility or primary infertility (p = 0.03, p = 0.048, respectively). In total, CDH 12 levels were significantly higher in patients diagnosed with infertility or primary infertility (p = 0.0092, p = 0.009, respectively) than in fertile women. Cadherin 12 can possibly play a role in the pathogenesis of infertility, both in women with and without endometriosis.

Plasma and Peritoneal Poly (ADP-Ribose) Polymerase Levels in Patients with Endometriosis.

The evidence of poly (ADP-ribose) polymerase (PARP) association with the immune response could be coherent with the immunological theory of endometriosis and suggests the possibility of a new research direction. The aim of the study was to evaluate the levels of PARP in plasma and peritoneal fluid of patients with and without endometriosis. It was a multicenter, cross-sectional study. Plasma and peritoneal fluid samples were collected from patients with and without endometriosis during planned laparoscopic procedures in eight clinical centers. In total, 84 samples of plasma and 84 samples of the peritoneal fluid were included in the final analyses. Double-antibody sandwich enzyme-linked immunosorbent assay was performed in order to assess levels of PARP in collected samples. No statistically significant differences regarding the detected levels of PARP in plasma and peritoneal fluid comparing patients with and without endometriosis were observed. Patients with a history of infertility had significantly higher plasma PARP concentrations (p = 0.04). We have not observed the potential role of PARP concentration levels in plasma nor peritoneal fluid as an endometriosis biomarker. We have determined an association between a higher plasma PARP concentration and a history of infertility.