Therapy For Polycystic Ovary Syndrome Research Articles

A Review of Medicinal Plants in the Therapy of Polycystic Ovary Syndrome (PCOS) in Woman

Context: Polycystic ovary syndrome (PCOS) is a neuroendocrine metabolic disorder, one of the symptoms of which is irregular menstrual cycles. Polycystic ovary syndrome treatment using chemical drugs has been effective, however, PCOS patients have received effective results from herbal treatment Methods: Scopus, PubMed, Google Scholar, Crossref and Hinari databases were searched for the effect of medicinal plants in the treatment of polycystic syndrome. Result: The results showed that medicinal plants and their active substances are effective in the treatment of polycystic syndrome. Conclusions: This study showed that the search and isolation of effective substances in plants can be a good treatment alternative for polycystic syndrome.

Myo-Inositol and D-Chiro-Inositol Reduce DHT-Stimulated Changes in the Steroidogenic Activity of Adult Granulosa Cell Tumors.

Considering the properties of myo-inositol (MI) and D-chiro-inositol (DCI), which are well known in polycystic ovary syndrome therapy, and the limitations of adult granulosa cell tumor (AGCT) treatment, especially for androgen-secreting tumors, we studied the role of MI and DCI in the androgen-rich environment of AGCTs. For this purpose, we analyzed the mRNA expression of steroidogenic genes and the secretion of progesterone (P4) and 17β-estradiol (E2) in an unstimulated and/or dihydrotestosterone (DHT)-stimulated environment under MI and DCI influence. Thus, we used the HGrC1 and KGN cell lines as in vitro models of healthy and cancerous granulosa cells. We found that DHT, the most potent androgen, increased E2 secretion and steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage gene (CYP11A1) mRNA expression without affecting 450 aromatase (CYP19A1) in AGCTs. However, after the MI and DCI treatment of KGN cells, both compounds strongly reduced StAR and CYP11A1 expression. Interestingly, in DHT-stimulated KGN cells, only DCI alone and its cotreatment with MI reduced both CYP11A1 mRNA and E2 secretion. These findings suggest that CYP11A1 is responsible for the antiestrogenic effect of DCI in the androgen-rich environment of AGCTs. Therefore, MI and DCI could be used as effective agents in the adjuvant treatment of AGCT, but further detailed studies are needed.

Polycystic ovary syndrome: new and promising treatment methods

Polycystic Ovary Syndrome (PCOS) - is a polygenic endocrine disorder caused by genetic, hormonal, and epigenetic factors. The importance of addressing PCOS lies in its prevalence, affecting approximately 10 to 13% of women, as well as the associated health conditions that can have a negative impact on women's lives, including infertility, dermatological manifestations of hyperandrogenism (such as hirsutism and acne), cardiovascular pathologies, metabolic disorders, and psychoemotional disorders. Currently, many theories of the development of this disease have been proposed, and as a consequence of methods of influencing and treating it. According to the clinical recommendations of the Ministry of Health of the Russian Federation, modifying the patient's lifestyle forms the basis of comprehensive therapy. We have analyzed about 60 articles on various dietary approaches to the treatment of PCOS, sourced from PubMed, Nature Reviews, Oxford Academic, Clinical Nutrition, EJOG, ScienceDirect, and MDPI. The Mediterranean diet, the DASH diet, the ketogenic diet and the low-carb diet have proven themselves the best. Also, it's necessary to add vitamin D, E, folic acid, calcium, various pro- and prebiotics to a woman's diet. Currently, the use of inositol and GPP-1 is becoming a promising method of PCOS therapy. According to the results of the analysis, a positive effect of diet therapy on the anthropometric and biochemical parameters was noted. Based on the analysis, a positive effect of diet therapy on anthropometric and biochemical parameters has been observed. It is crucial to consider the individual characteristics of each patient and not rely solely on drug therapy when approaching the treatment of PCOS.

Potential of Curcumin in Curcuma Longa as an Alternative Therapy for PCOS: A Literature Review

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine hormone disorder in women of childbearing age with a global incidence of 8-13%. The use of medical drugs in the long term can cause serious side effects so that the utilization of curcumin contained in Curcuma longa can be an alternative therapy consideration for PCOS. This paper will discuss the potential and benefits of curcumin content as an alternative therapy for PCOS. The method used, namely by reviewing the literature in national and international journals that are in accordance with the objectives of the review. The results of the literature review show that curcumin has effectiveness in treating PCOS through various mechanisms of action accompanied by minimal side effects. Alternative therapy of PCOS by taking curcumin needs to consider the dose, duration of use, and further research with larger subjects in assessing its effectiveness and side effects. However, it is suspected that nanocurcumin formulations have higher bioavailability and solubility than free curcumin, giving it even greater potential in the treatment of PCOS in the future. In conclusion, curcumin has the potential as an alternative therapy for PCOS that requires further research to achieve the optimization of PCOS treatment in the future.

SFRP4 contributes to insulin resistance-induced polycystic ovary syndrome by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overproduction of androgens. Women with PCOS are commonly accompanied by insulin resistance (IR), which can impair insulin sensitivity and elevate blood glucose levels. IR promotes ovarian cysts, ovulatory dysfunction, and menstrual irregularities in women patients, leading to the pathogenesis of PCOS. Secreted frizzled-related protein 4 (SFRP4), a secreted glycoprotein, exhibits significantly elevated expression levels in obese individuals with IR and PCOS. Whereas, whether it plays a role in regulating IR-induced PCOS still has yet to be understood. In this study, we respectively established in vitro IR-induced hyperandrogenism in human ovarian granular cells and in vivo IR-induced PCOS models in mice to investigate the action mechanisms of SFRP4 in modulating IR-induced PCOS. Here, we revealed that SFRP4 expression levels in both mRNA and protein were remarkably upregulated in the IR-induced hyperandrogenism with elevated testosterone in the human ovarian granulosa cell line KGN. Under normal conditions without hyperandrogenism, overexpressing SFRP4 triggered the remarkable elevation of testosterone along with the increased nuclear translocation of β-catenin, cell apoptosis and proinflammatory cytokine IL-6. Furthermore, we found that phytopharmaceutical disruption of SFRP4 by genistein ameliorated IR-induced increase in testosterone in ovarian granular cells, and IR-induced PCOS in high-fat diet obese mice. Our study reveals that SFRP4 contributes to IR-induced PCOS by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis. Elucidating the role of SFRP4 in PCOS may provide a novel therapeutic strategy for IR-related PCOS therapy.

Pterostilbene Ameliorates Cognitive Impairment in Polycystic Ovary Syndrome Rat Model through Improving Insulin Resistance via the IRS-1/PI3K/Akt/GSK-3β Pathway: A Comparative Study with Metformin.

Polycystic ovary syndrome (PCOS) is an intricate endocrine disorder that targets millions of women globally. Recent research has drawn attention to its association with cognitive impairment and Alzheimer's disease (AD) risk, yet the exact mechanism remains elusive. This study aimed to explore the potential role of PCOS-associated insulin resistance (IR) and inflammation in linking PCOS to AD pathogenesis. It additionally investigated the therapeutic merits of pterostilbene (PTS) in ameliorating PCOS and associated cognitive deficits in comparison to metformin (MET). Rats were divided into five groups; vehicle group, PTS group [30 mg/kg, per os (p.o.) for 13 days], and the remaining three groups received letrozole (1 mg/kg, p.o. for 21 days) to represent the PCOS, PCOS + MET (300 mg/kg, p.o. for 13 days), and PCOS + PTS groups, respectively. Behavioral tests were conducted, along with a histopathological investigation of brains and ovaries. Assessment of serum hormonal profile and hippocampal IRS-1/PI3K/AKT/GSK-3β insulin signaling pathway components were performed. PTS rats exhibited improved insulin sensitivity and hormonal profile, besides enhanced neurobehavioral tests performance and histopathological findings. These effects may be attributed to modulation of the IRS-1/PI3K/AKT/GSK-3β pathway, reducing GSK-3β activity, and mitigating Tau hyperphosphorylation and Aβ accumulation in the brain. Likewise, PTS attenuated nuclear factor kappa B-mediated inflammation and reversed AChE elevation, suggesting multifaceted neuroprotective effects. Comparatively, PTS showed outcomes similar to those of MET in most parameters. The obtained findings validated that dysregulated insulin signaling in PCOS rats detrimentally affects cognitive function, which is halted by PTS, unveiling the potential of PTS as a novel therapy for PCOS and related cognitive deficits.

Diagnosis, Management, and Associated Comorbidities of Polycystic Ovary Syndrome: A Narrative Review.

Polycystic ovary syndrome (PCOS) is the most widespread and diverse endocrine health issue affecting many adolescent-aged women globally. It is the most frequent illness in reproductive-aged women. According to the Rotterdam criteria, two out of three elements: oligo-anovulation, hyperandrogenism, and polycystic ovaries (defined as having at least one ovary with an ovarian volume > 10 mL and/or 12 or more follicles measuring 2 to 9 mm in diameter) are present in PCOS. Conducted studies show epigenetics, environmental toxins, stress, and food as external factors as well as inflammation, oxidative stress, hyperandrogenism, insulin resistance, and obesity as internal factors related to PCOS. Although a portion of the mechanism associated with the occurrence of PCOS has been identified, there is still much to learn about the exact etiology and pathophysiology. The main debate covers the best ways to diagnose and treat this disease in adolescents. Early detection is crucial because of the disease's long-term effects on metabolic and reproductive health. Before beginning treatment for this group of young women, a firm diagnosis may not be made. Various criteria are used to diagnose PCOS patients. A person with PCOS has a chance of developing several comorbidities and health effects. PCOS patients are at risk of cardiac diseases, metabolic syndromes, resistance to insulin, infertility, and many more. There are numerous medications available for PCOS therapy that need a methodical approach. However, changing one's lifestyle should come first. There is proof in the support of the usage of several medications for PCOS, including mucolytic agents, Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, gliptins (oral diabetic medication), glucose-like peptide-1 receptor analogues, glitazones, and sodium-glucose cotransporter protein-2 (SGLT2) inhibitors. A comprehensive, systematic, schematic therapy approach is crucial for the treatment of PCOS.

LncRNA XIST Protects Against Polycystic Ovary Syndrome via the Regulation of miR-212-3p/RASA1 Axis.

The polycystic ovary syndrome (PCOS), a common endocrine disorder, is mainly related to infertility. Moreover, it is characterized by promoted androgen, suppressed ovulation and insulin resistance. Long non-coding RNA X inactive specific transcript (lncRNA XIST), known as an oncogene or a cancer inhabited factor, is involved in several disease. However, the diagnostic mechanisms of lncRNA XIST in PCOS have not been clarified. Our study aimed to explain whether lncRNA XIST regulates KGN cells proliferation and apoptosis via microRNA (miR)-212-3p/RASA1 axis in PCOS. Levels of lncRNA XIST, miR-212-3p and RASA1 in KGN cells were detected through reverse transcription quantitative polymerase chain reaction (RT-qPCR) assay. Fluorescence in situ Hybridization (FISH) was performed to confirm the expression of lncRNA XIST and miR-212-3p in KGN cells. StarBase and dual-luciferase reporter assay were applied for exploring the interaction between miR-212-3p and RASA1. Cell viability, apoptosis, protein expression of Bcl-2 and Bax were assessed by MTT, flow cytometry analysis, RT-qPCR and western blot, respectively. We found that lncRNA XIST was low-expressed, miR-212-3p was over-expressed, and RASA1 was dramatically down-regulated in KGN cells. LncRNA XIST negatively regulated miR-212-3p expression in KGN cells. MiR-212-3p interacted with RASA1 and negatively regulated RASA1 levels in KGN cells. Up-regulation of lncRNA XIST signally decreased cells viability, stimulated more apoptotic cells, enhanced Bax expression, and depressed Bcl-2 level in KGN cells. However, these observations were abolished after miR-212-3p mimic treatment. Furthermore, miR-212-3p inhibitor significantly inhibited cell proliferation, enhanced more apoptotic cells, increased Bax expression, and decreased Bcl-2 level in KGN cells, and these effects were eliminated by RASA1-siRNA transfection. Our observations revealed that lncRNA XIST protects against PCOS through regulating miR-212-3p/RASA1 axis, suggesting that lncRNA XIST may be a promising therapeutic target for PCOS therapy.

Cellular senescence of granulosa cells in the pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, but its pathology has not been fully characterized and the optimal treatment strategy remains unclear. Cellular senescence is a permanent state of cell-cycle arrest that can be induced by multiple stresses. Senescent cells contribute to the pathogenesis of various diseases, owing to an alteration in secretory profile, termed 'senescence-associated secretory phenotype' (SASP), including with respect to pro-inflammatory cytokines. Senolytics, a class of drugs that selectively eliminate senescent cells, are now being used clinically, and a combination of dasatinib and quercetin (DQ) has been extensively used as a senolytic. We aimed to investigate whether cellular senescence is involved in the pathology of PCOS and whether DQ treatment has beneficial effects in patients with PCOS. We obtained ovaries from patients with or without PCOS, and established a mouse model of PCOS by injecting dehydroepiandrosterone. The expression of the senescence markers p16INK4a, p21, p53, γH2AX, and senescence-associated β-galactosidase and the SASP-related factor interleukin-6 was significantly higher in the ovaries of patients with PCOS and PCOS mice than in controls. To evaluate the effects of hyperandrogenism and DQ on cellular senescence in vitro, we stimulated cultured human granulosa cells (GCs) with testosterone and treated them with DQ. The expression of markers of senescence and a SASP-related factor was increased by testosterone, and DQ reduced this increase. DQ reduced the expression of markers of senescence and a SASP-related factor in the ovaries of PCOS mice and improved their morphology. These results indicate that cellular senescence occurs in PCOS. Hyperandrogenism causes cellular senescence in GCs in PCOS, and senolytic treatment reduces the accumulation of senescent GCs and improves ovarian morphology under hyperandrogenism. Thus, DQ might represent a novel therapy for PCOS.

Immune dysfunction mediated by the competitive endogenous RNA network in fetal side placental tissue of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder affecting women in their reproductive years. Emerging evidence suggests that the maternal-fetal immune system is crucial for proper pregnancy. However, whether immune function is altered at the end of pregnancy in PCOS women and the underlying molecular mechanisms is currently unexplored. Herein, the basic maternal immune system was investigated (n = 136 in the control group; n = 103 in the PCOS group), and whole-transcriptome sequencing was carried out to quantify the mRNAs, miRNAs, and lncRNAs expression levels in fetal side placental tissue of women with PCOS. GO, KEGG, and GSEA analysis were employed for functional enrichment analysis. The process of identifying hub genes was conducted utilizing the protein-protein interaction network. CIBERSORT and Connectivity Map were deployed to determine immune cell infiltration and predict potential drugs, respectively. A network of mRNA-miRNA-lncRNA was constructed and then validated by qRT-PCR. First, red blood cell count, neutrophil count, lymphocyte count, hypersensitive C-reactive protein, and procalcitonin were significantly elevated, while placental growth factor was hindered in PCOS women. We identified 308 DEmRNAs, 77 DEmiRNAs, and 332 DElncRNAs in PCOS samples. Functional enrichment analysis revealed that there were significant changes observed in terms of the immune system, especially the chemokine pathway. Eight genes, including FOS, JUN, EGR1, CXCL10, CXCR1, CXCR2, CXCL11, and CXCL8, were considered as hub genes. Furthermore, the degree of infiltration of neutrophils was dramatically decreased in PCOS tissues. In total, 57 ceRNA events were finally obtained, and immune-related ceRNA networks were validated. Some potential drug candidates, such as enalapril and RS-100329, could have a function in PCOS therapy. This study represents the inaugural attempt to evaluate the immune system at the end of pregnancy and placental ceRNA networks in PCOS, indicating alterations in the chemokine pathway, which may impact fetal and placental growth, and provides new therapy targets.

Optimizing vitamin D status in polycystic ovary syndrome: a systematic review and dose-response meta-analysis.

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines. The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS. MEDLINE, CINAHL, and EMBASE databases from inception to November 2022 were searched for relevant articles. Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean ± SD) and vitamin D dose were extracted. Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose-response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification. Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears minimal. Further data is required to determine dose-response at doses of >5000 IU/day, and whether higher intakes provide a clinically meaningful advantage in this population. PROSPERO registration no. CRD42021259396.

Effects of KISS1 structural polymorphism on the risk of polycystic ovary syndrome and reproductive hormones in Iraqi women who take metformin.

To identify the effects of metformin and kisspeptin structural polymorphism on the risk of polycystic ovary syndrome (PCOS) in Iraqi women. Samples were collected at the family planning center of Al-Hassan Teaching Hospital (infertility clinic), Iraq. Hormonal and hematological parameters were measured. Kisspeptin structural polymorphisms were analyzed by polymerase chain reaction using a conventional thermal cycler and Phyre2 predictions. Kisspeptin concentrations were assessed by an enzyme-linked immunosorbent assay. Follicle-stimulating hormone (FSH) was the only sex hormone that changed in women with PCOS after metformin treatment. FSH concentrations were significantly increased after therapy compared with before therapy (9.39 ± 2.1 vs 5.13 ± 1.53 IU/L). We found that a single nucleotide polymorphism substituting G to C was related to PCOS. The kisspeptin structural polymorphism showed that the C allele was related to low FSH concentrations after treatment (6.92 ± 2.2 IU/L to 5.34 ± 1.58 IU/L). Kisspeptin concentrations were significantly lower after metformin treatment than before metformin treatment (395.44 ± 67.83 vs 273.18 ± 42.98 ng/mL). A variation in the KISS1 gene or its protein structure may be involved in the development of PCOS. The response to metformin may be used as an indicator and could contribute to the early diagnosis and medical therapy of PCOS.

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome.

Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese medicinal plants showing a tight correlation with gut microbiota. Polycystic ovary syndrome (PCOS) is a prevalent reproductive and endocrine disorder syndrome among women of childbearing age. Dysbiosis, the imbalance of intestinal microorganisms, is a potential factor that takes part in the pathogenesis of PCOS. Recent evidence indicates that berberine offers promise for treating PCOS. Here, we review the recent research on the interaction between berberine and intestinal microorganisms, including the changes in the structure of gut bacteria, the intestinal metabolites after BBR treatment, and the effect of gut microbiota on the bioavailability of BBR. We also discuss the therapeutic effect of BBR on PCOS in terms of gut microbiota and its potential mechanisms.

Relationship between eating patterns and emotional distress, and perceived quality of life in women with polycystic ovarian syndrome.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with numerous hormonal, metabolic, and reproductive manifestations. Because of the variety of adverse consequences associated with the condition, women with PCOS suffer emotional distress, resulting in reduced health-related quality of life. Similar to other chronic conditions, eating patterns have been shown effective in impacting the quality of life of PCOS patients. Therefore, lifestyle modifications are recommended as a first-line therapy for PCOS, before prescribing any pharmaceutical management of the PCOS. The aim of the study was to investigate the relationship between dietary patterns, emotional distress, and perceived quality of life in women with diagnosed PCOS. The cross-sectional study included 130 women with PCOS aged 18 - 60 years from the Polish population. The respondents were asked to complete a self-administered questionnaire developed for the purpose of the study, inspired by the Food Frequency Questionnaire (FFQ), Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ), Three-Factor Eating Questionnaire (TFEQ-R18), and the Eating attitude questionnaire (Eat-26). Respondents were found to experience emotional distress regardless of how healthy their diet. Nonetheless, the results showed that women who followed a healthier eating pattern had lower occurrence of experiencing mood swings, and less often felt triggered in the social context. The group did not show a tendency to over-eat, gain weight, or binge eating. Healthier eating habits, besides providing advantages in weight management, may mitigate symptoms of emotional distress and improve the quality of life in women with PCOS.

Brown adipose tissue in the form of innovative approach for polycystic ovary syndrome treatmentstill long time to reach clinical arena: a narrative review

Brown adipose tissue(BAT)portrays a specialized tissue, possessing a crucial part in metabolism as well as energy expenditure(EE) via adaptive non shivering thermogenesis .Recently it has assumed a significant part in the treatment of obesity along with metabolic disease.The thermogenesis action of BAT is brought about by uncoupling protein1 (UCP1 ),that uncouples adenosine triphosphate (ATP) generation from oxidation of energy substrates.Having reviewed earlier various aspects of Polycystic ovary syndrome (PCOS) pathophysiology,treatment,role in trans generational PCOS transferalong with role of BAT pathophysiology,beige/brite adipocytes in the treatment of obesity along with metabolic disease here we decided to further evaluate the possible part of (BAT in PCOS. Thus anarrative review was carried out using the pubmed, Web of Science , Medline, Embase, Cochrane reviews, and Google Scholar, Search engine with the MeSH Terms;PCOS; impaired lipid metabolism; Brown Adipose tissue (BAT); White Adipose tissue(WAT); oxidative stress;inflammation;obesity ;T2DM); Type 1 diabetes (T1D); role of natural substances for PCOStherapy like rutin ,berberine;resveratrol ; weight reduction; browning of WAT ;Macrophage Polarization from 1990 till date in 2023.We found a total of 250 articles ,out of which we selected 100 articles for this review.No meta-analysis was done.The endocrine action of brown Adipocytes impacts the energy balanceof glucose as well as lipid homeostasis thus impacting the correlation of BAT activity along with metabolic profile . PCOS mirrors a , complicated reproductive as well asmetabolic condition of women in their reproductive age . functional aberrations in adipose tissue have been illustrated in PCOS patients .Multiple studies have illustrated that BAT possesses the capacity of controlling the properties of PCOS as well as escalating BAT mass/activity were efficacious in the therapy of PCOS. Via cold stimulation,BAT transplantation as well as activationwith substances like rutin hypoglycemia can be attained.

Identification of the hub genes in polycystic ovary syndrome based on disease-associated molecule network.

Revealing the key genes involved in polycystic ovary syndrome (PCOS) and elucidating its pathogenic mechanism is of extreme importance for the development of targeted clinical therapy for PCOS. Investigating disease by integrating several associated and interacting molecules in biological systems will make it possible to discover new pathogenic genes. In this study, an integrative disease-associated molecule network, combining protein-protein interactions and protein-metabolites interactions (PPMI) network was constructed based on the PCOS-associated genes and metabolites systematically collected. This new PPMI strategy identified several potential PCOS-associated genes, which have unreported in previous publications. Moreover, the systematic analysis of five benchmarks data sets indicated the DERL1 was identified as downregulated in PCOS granulosa cell and has good classification performance between PCOS patients and healthy controls. CCR2 and DVL3 were upregulated in PCOS adipose tissues and have good classification performance. The expression of novel gene FXR2 identified in this study is significantly increased in ovarian granulosa cells of PCOS patients compared with controls via quantitative analysis. Our study uncovers substantial differences in the PCOS-specific tissue and provides a plethora of information on dysregulated genes and metabolites that are linked to PCOS. This knowledgebase could have the potential to benefit the scientific and clinical community. In sum, the identification of novel gene associated with PCOS provides valuable insightsinto the underlying molecular mechanisms of PCOS and could potentially lead to the development of new diagnostic and therapeutic strategies.

The role of metabolic syndrome in the development of polycystic ovary syndrome in adolescence

The review article presents an analysis of the metabolic syndrome problem in children and adolescents, its role in the development of polycystic ovary syndrome (PCOS) in accordance with the latest International guidelines and modern literature. The urgency of the problem lies in the rapid spread of overweight among children in the world and, consequently, the growth of alimentary-dependent pathology. One of the major consequences of weight problems is metabolic syndrome (MS). There are still no clear MS criteria for children and adolescents. IDF suggests using IDF criteria for adults. Priority in the pathogenesis of MS is given to insulin resistance (IR), which is associated with puberty. The problem of IR assessment remains. HOMA-IR and QUICKI methods are not considered reliable tests to determine IR, so the assessment is based on clinical signs (hyperglycemia, dyslipidemia, abdominal obesity, hypertension). Obesity and IR can be predictors of PCOS, which can often be associated with puberty. Pathological signs of the syndrome typical for adults in adolescence may be a manifestation of the physiological course of puberty. Obligative criteria for the diagnosis of PCOS in adolescence are irregular menstruation/oligomenorrhea, proven biochemically and clinically hyperandrogenemia). First-line therapy for PCOS in adolescents with MS is weight loss and dosed exercise, which helps to normalize a hormonal balance. Drug treatment may include insulin-sensitizing drugs (metformin), antiandrogens (spironlactone, flutamide, cyproterone acetate), 5-alpha-reductase inhibitors (finasteride), combined oral contraceptives, inositol. Prevention of overweight, obesity in children can prevent the development of IR and, accordingly, associated MS and PCOS, reproductive health disorders. Prevention measures are aimed at avoiding maternal obesity, gestational diabetes, malnutrition and smoking during pregnancy, promoting breastfeeding and physical activity.

LC-MS/MS based quantification of steroidal biomarkers in polycystic ovary syndrome induced rats

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that causes reproductive hormones imbalance, missed periods, infertility and distributed steroidogenesis. Reportedly, during PCOS, the endogenous levels of P4 (Progesterone), 17OHP4 (17-α hydroxy progesterone), and T4 (Testosterone) were significantly altered. Thus, quantification of steroid biomarkers involved in the steroidogenesis pathway of PCOS, such as P4, 17OHP4, and T4, holds significant importance. One important drawback of current methods is steroid metabolome traceability. Without adequate traceability, the findings of these techniques will be less reliable for identifying P4, 17OHP4, and T4. These methods also need a high sample size, especially for the most important biomarker that initiates steroidogenesis. To address these challenges, we require a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for steroid biomarker analysis. Herein the present work, using validated LC-MS/MS, PCOS biomarkers were measured and compared between normal control rats and PCOS-induced rats before and after analyte administration. The experiment utilized an isocratic separation method employing an analytical C18 column. The mobile phase consisted of acetonitrile (ACN) and aqueous 0.1% formic acid (FA) in a ratio of 90:10 (v/v). The plasma samples were processed with protein precipitation (PPT) followed by the liquid-liquid extraction (LLE) method. The lower limit of quantification (LLOQ) was 0.5 ng/mL in plasma. According to USFDA criteria, the method's systematic validation took into account linearity (r2 > 0.99), accuracy and precision of intra- and inter-batch measurements, stability, biomarker recovery (60–85%) and matrix effect (<± 15%), all of which were determined to be within range ( ± 15%). The pharmacokinetic data showed that, as compared to normal rats, PCOS-induced animals had significantly higher Cmax values for 17OHP4 and T4 (∼2 fold), while lower Cmax values for P4 (∼2 fold). The present work is novel and provides scientific information to explore systematic processes involved in steroidogenesis and boost clinical applicability for PCOS therapy.

Metabolic dysfunction correction as a method of restoring the function of the reproductive system in women

Insulin resistance is the main pathogenetic component of many metabolic diseases, including obesity, type 2 diabetes mellitus, gestational diabetes mellitus, and polycystic ovary syndrome (PCOS). Despite the fact that to date the mechanisms of insulin resistance formation have not been established, one of the promising directions at present is the search for potential therapeutic strategies for its correction, due to the fact that this also improves the course of the concomitant underlying disease. Insulin sensitizers are a generally recognized method of PCOS therapy due to their safety and effectiveness in normalizing the metabolic and endocrine profile of patients with polycystic ovary syndrome. The leading position in this direction is occupied by the combination of myo-inositol (MI) with D-chiro-inositol (DHI) in a ratio of 40:1, which, according to the conducted studies, is comparable to the concentration of inositols in the blood plasma of healthy women. This ratio of MI/DHI is effective both for normalization of the metabolic profile, and for regulation of the menstrual cycle and overcoming anovulatory infertility. An analysis of the literature has shown that a number of biologically active substances, such as folic acid, vitamin D and alpha-lipoic acid, in combination with insulin sensitizers, have additional advantages, which gives grounds for continuing research on their significance as components of combined treatment, as well as in the search for the optimal dose and duration of such therapy.

Target therapy of polycystic ovary syndrome

Due to the complexity of the diagnosis and treatment of polycystic ovary syndrome (PCOS) in adolescents, studies are currently underway to select targeted therapy to normalize the metabolic and reproductive status of girls, including those at risk for PCOS. There are a lot of researches, that evaluate the effectiveness of inositol therapy in PCOS, ovarian dysfunction, insulin resistance (IR), ovarian hyperandrogenism in both adolescents and adult women, including those in IVF cycles. Currently, the choice of determining the ratio of myo-inositol (MI) and d-chiro-inositol (DCI) for the treatment of PCOS often leads to the physiological proportion of inositols in plasma (40:1), since research results are insufficient to unambiguously confirm it. In this connection, there is a large number of pharmaceuticals without or with a low dosage of DCI, that can’t bypass the defective epimerase activity and achieve an adequate level of DCI in the ovaries. Determination of a fair assessment and dosage of MI/DCI is required for long-term correction of metabolic, endocrinological and clinical manifestations of various PCOS phenotypes. Inositols are promising and safe treatment of hyperandrogenism, obesity, insulin resistance in women of various age groups and can also effectively complement a therapeutic effect of metformin and combined oral contraceptives.