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.

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.

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.

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.

A novel estetrol-containing combined oral contraceptive: European expert panel review.

PURPOSE: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. MATERIALS AND METHODS: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. RESULTS: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg. CONCLUSION: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

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.

The impact of surgical treatment of obesity on the female fertility.

As obesity is considered to be a pandemic of the twenty-first century, the bariatric surgery becomes more common through the global population. The adverse effects of obesity on fertility can be reversed through the bariatric surgery procedures. In this review, we presented the effects of bariatric surgery on hypothalamic-pituitary-ovarian axis and fertility, ovarian reserve, and contraception efficacy.

[Selected legal aspects of the protection of the unborn child in the light of the draft amendment to the Polish Penal Code]. / Wybrane aspekty prawne ochrony dziecka poczetego w swietle projektu nowelizacji Kodeksu Karnego.

Criminal Law Codification Commission, acting at the Ministry of Justice prepared proposals for amendments in the Polish Penal Code, related to offenses against life and health that were presented to the public in 2013. The draft provides for the protection of the child in the prenatal stage, introducing a new category of the entity to be protected, which is "unborn child" and "unborn child able to live outside the mother's body". These regulations provide for mothers criminal liability and responsibility of the medical staff (a doctor), as well as the child's father to the extent in which he is obliged to take steps aimed at rescuing the fetus. It is doctor's responsibility to show particular care for human health and life since a doctor has special medical knowledge and that is regulated by art. 30 of the act on professions of doctor and dentist. The proposed rule changes were not brought before the legislature in the current term of the Sejm (2011-2015), but due to the development of medicine, including obstetrical ultrasound, which enables visualization of a child that moves in the womb and is treated as a separate entity with distinct personal features the grounds are given for the opinion that the issue of the legal status of the unborn child, particularly in the context of causing death of a child in the last phase before birth as a result of medical malpractice or other external factors will be back in the public discussion.

[Assisted reproductive medicine in Poland, 2011--SPiN PTG report]. / Medycyna wspomaganego rozrodu w Polsce--raport za rok 2011 Sekcji Plodnosci i Nieplodnosci Polskiego Towarzystwa Ginekologicznego (SPiN PTG).

AIM: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2011. MATERIALS AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics in Poland. Reporting was voluntary and the provided data was not subject to external control. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. MAIN RESULTS: In 2013, 33 Polish fertility clinics provided information to the SPiN PTG report, presenting data from the year 2011. The total number of reported treatment cycles using ART was 15,340 (incl. 10,011 IVF/ICSI procedures) and 15,627 IUI procedures. The rate of clinical pregnancies in terms of a cycle was 34.2% in case of IVF/ ICSI procedures and 13.4% in case of IUI. The prevalence of multiple births was 20.2% and 8.3% respectively in case of IVF/ICSI and IUI methods. The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS). CONCLUSION: The SPiN PTG report allows to find out the average effectiveness and safety of assisted reproduction technologies and is currently the only proof of responsibility and due diligence of fertility centres in Poland. However due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery the collected data does not reflect the full spectrum of the Polish reproductive medicine.

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.

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.

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.

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.

[Legal aspects of selling medical products by gynecologists]. / Aspekty prawne sprzedazy produktów leczniczych przez lekarza ginekologa.

Sales and distribution of medical products and drugs in Poland remains under strict regulations, especially legal regulation contained in the Medical and Dental Practitioners Act, that banned sales of medical products by doctors. It needs to be emphasized that currently doctors are allowed to sell drugs and medical products only in rigorously specified situations. Knowledge of current legal regulations concerning sales of medical products by gynecologists allows to conform with the law and to distribute drugs and medical products under special and predefined conditions.

Steroidogenic activity of liposomal methylated resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model.

PURPOSE: Steroid hormone secretion is one of the key functions of granulosa cells (GCs). Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. The methoxy derivative of resveratrol (DMU-212) was demonstrated to be more lipophilic, and therefore of greater bioavailability. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model. METHODS: DMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to the liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze the expression of steroidogenesis-related genes. Finally, the western blot technique was used to analyze the effect of lipDMU-212 and FSH treatments on CYP11A1 and HSD3B1 protein levels. RESULTS: lipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing the expression of CYP11A1, HSD3B1, StAR, CYP17A1, CYP19A1, and HSD17B1 genes. We have also shown that lipDMU-212, used alone and in combination with FSH, significantly increased the expression of the HSD3B1 and CYP11A1 proteins in GCs. Furthermore, our study suggests that lipDMU-212 increases FSH activity. CONCLUSIONS: This is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.

GnRH agonists and antagonists in therapy of symptomatic uterine fibroids - current roles and future perspectives.

INTRODUCTION: Uterine fibroids are the most common noncancerous tumors in women of childbearing age. This review was developed to evaluate the current role of gonadotropin-releasing hormone (GnRH) agonists and antagonists in the therapy of symptomatic uterine fibroids. AREAS COVERED: There is a great need for alternative methods for surgical treatment of uterine fibroids. Hormonal therapy remains the first-line treatment option for most patients. GnRH analogs (agonists and antagonists) modulate the pulsatile release of GnRH. This review summarizes the available literature concerning pharmacologic principles underlying the mechanism of action of GnRH and its analogs, as well as individual therapeutic applications to which these drugs have been applied. EXPERT OPINION: In many cases, it is possible to try to treat uterine fibroids pharmacologically. Both groups of GnRH analogs are used in therapy, agonists instead as a preparation for surgery, and antagonists as a drug for long-term use. It is essential to develop this path further and look for at least long-term-release systems or new methods of administering these drugs. It is also important from the patient's perspective to search for possible drugs that may have an additive effect of decreasing side effects when combined with GnRH analogs.

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.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

[Results of pap smears and immunocytochemical detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia and cervical cancer]. / Wyniki badan cytologicznych i immunocytochemiczna identyfikacja bialek p16 i Ki67 u kobiet ze sródnablonkowa neoplazja i rakiem szyjki macicy.

OBJECTIVE: The aim of the study was to assess the diagnostic value of pap smears and detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia (CIN). MATERIALS AND METHOD: 630 women, aged between 25 and 65, with abnormal pap smears were included into the study All patients had a control pap smear and in each case punch biopsy with endocervical curettage were performed under the control of a colposcope. The presence of p16 and Ki67 proteins was detected using the CINtecPlus test. The results of the research were statistically assessed. RESULTS: Abnormal pap smears were found in 82.5% (520/630) of the studied women. In 40% (252/630) of the cases the LSIL changes were found. The recognition of ASC-US concerned 35.2% (222/630) of the patients, and pap smears with the HSIL result were found in 7.3% (46/630) of the women. In 17.5% (110/630) of the patients the result of the cytological examination was normal. Abnormal results of the pap smears were found significantly statistically more frequently (p<0,0001) in women with cervical intraepithelial neoplasia (CIN). The results of the CINtecPlus test were positive in 68,4% of women with CIN and in 33,3% of patients with normal cervix. In the group of women with precancerous lesions (HGSIL/CIN2+) the diagnostic accuracy of the pap smear was 41% for the cytological results ASC-US, 56% LSIL and 73% for detection of HSIL. Immunocytochemical detection of p16 and Ki67 proteins gained the highest accuracy (78%) in recognition of cervical precancerous lesions. CONCLUSION: 1. ASC-US and LSIL cytological recognition has low accuracy in the diagnosis of CIN2+ cervical changes. 2. Cytological recognition of HSIL has the highest accuracy in the diagnosis of CIN2+ changes. 3. Immunocytochemical detection of p16 and Ki67 proteins is more accurate in recognizing precancerous states and cervical cancer than cytological examination. 4. Immunocytochemical detection of the p16 and Ki67 proteins can be used to triage patients with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions.