Polycystic Ovary Syndrome Disorders Research Articles

DENND1A desensitizes granulosa cells to FSH by arresting intracellular FSHR transportation.

Polycystic ovary syndrome (PCOS) is a complex disorder. Genome-wide association studies (GWAS) have identified several genes associated with this condition, including DENND1A. DENND1A encodes a clathrin-binding protein that functions as a guanine nucleotide exchange factor involved in vesicular transport. However, the specific role of DENND1A in reproductive hormone abnormalities and follicle development disorders in PCOS remain poorly understood. In this study, we investigated DENND1A expression in ovarian granulosa cells (GCs) from PCOS patients and its correlation with hormones. Our results revealed an upregulation of DENND1A expression in GCs from PCOS cases, which was positively correlated with testosterone levels. To further explore the functional implications of DENND1A, we generated a transgenic mouse model overexpressing Dennd1a (TG mice). These TG mice exhibited subfertility, irregular estrous cycles, and increased testosterone production following PMSG stimulation. Additionally, the TG mice displayed diminished responsiveness to FSH, characterized by smaller ovary size, less well-developed follicles, and abnormal expressions of FSH-priming genes. Mechanistically, we found that Dennd1a overexpression disrupted the intracellular trafficking of follicle stimulating hormone receptor (FSHR), promoting its internalization and inhibiting recycling. These findings shed light on the reproductive role of DENND1A and uncover the underlying mechanisms, thereby contributing valuable insights into the pathogenesis of PCOS and providing potential avenues for drug design in PCOS treatment.

Polycystic ovary syndrome and metabolic syndrome: possible ways to correct metabolic disorders

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproductive age. The prevalence of this pathology is approximately 15-20%. PCOS is characterized by hyperandrogenism, hirsutism, menstrual irregularities, and polycystic ovaries. More than half of patients with PCOS have a metabolic syndrome, the main component of which is visceral obesity and insulin resistance, which play an important role in the pathophysiology of PCOS. Insulin resistance is a marker of cardiometabolic risk and can lead to cardiovascular disease and carbohydrate metabolism disorders up to type 2 diabetes mellitus (DM2). Therefore, in the treatment of patients with PCOS, an important aspect is the impact on insulin sensitivity and body weight. This review focuses on various groups of drugs that can potentially have a positive effect on metabolic disorders in PCOS. Among them are metformin, drugs with an incretin effect, as well as drugs for weight loss. Given the similarity of the metabolic and pathological features of PCOS and DM2, as well as the diversity of therapeutic options, there is a potential for expanding the strategy for the treatment of metabolic disorders in PCOS, including through antidiabetic drugs, which, however, requires further study. It should be noted that surgical treatment of obesity also has a beneficial effect and contributes to the normalization of the menstrual cycle and the normalization of the hormonal and metabolic profile in patients with PCOS and severe obesity.

Body Composition Parameters, Adiponectin, Leptin and Adiponectin/Leptin Ratio are Correlated with LH/FSH Ratio in Women with PCOS but not in Women without PCOS

Objective: To investigate the correlation between body composition parameters, adiponectin, leptin and the adiponectin/leptin ratio and the LH/FSH ratio in women with polycystic ovary syndrome (PCOS).
 Methods: A cross-sectional study was conducted at Reproductive Cluster Yasmin, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, with sixty women with PCOS and sixty healthy women as controls (matched for age and BMI). Body composition parameters, including body weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), percent subcutaneous fat (PSF) and skeletal muscle mass (SMM), were measured; levels of fasting glucose, fasting insulin, testosterone, and sex hormone binding globulin (SHBG) were measured; and homeostatic model assessment for insulin resistance (HOMA-IR) values, anti-Mullerian hormone (AMH), free androgen index (FAI), Ferriman-Gallwey (FG) score, adiponectin levels, leptin levels, adiponectin/leptin ratio, LH, FSH and LH/FSH ratio were measured.
 Results: Body composition parameters (body weight, BMI, WC, WHR, PBF, VFA, PSF, SMM) were not significantly different between women with PCOS and controls. Fasting insulin (P<0.05), HOMA-IR (P<0.05), AMH (P<0.01), FAI (P<0.01), FG score (P<0.01) and LH/FSH ratio (P<0.05) were higher in PCOS women. Adiponectin (P<0.01) was lower in PCOS women, while leptin and the adiponectin/leptin ratio were not significantly different between groups. Most of body composition parameters, adiponectin, leptin and adiponectin/leptin ratio were correlated with HOMA-IR in both groups.
 SMM was positively correlated with the LH/FSH ratio, while body weight, BMI, WC, PBF, VFA, and PSF were inversely correlated with the LH/FSH ratio in PCOS patients but not in controls. WHR was not correlated in either group. Leptin (r=-0.278; P<0.05) was negatively correlated with the LH/FSH ratio only in the PCOS group. Adiponectin (r=0.394; P<0.01) and the adiponectin/leptin ratio (r=0.413; P<0.01) were also positively correlated with the LH/FSH ratio only in the PCOS group. AMH was correlated with the LH/FSH ratio, whereas testosterone level, FAI, FG score, fasting insulin level and HOMA-IR value were not correlated with the LH/FSH ratio in PCOS women.
 Conclusion: Most of the body composition parameters, leptin, adiponectin and the adiponectin/leptin ratio were significantly correlated with HOMA-IR in both groups. However, correlations of those parameters with LH/FSH ratio were found only in PCOS but not in women without PCOS. Adiponectin and leptin may play a significant role in the mechanism of neuroendocrine disorders in PCOS, which is characterized by an increased LH/FSH ratio.
 Keywords: adiponectin, adiponectin/leptin ratio, body composition, HOMA-IR, leptin, LH/FSH ratio, PCOS

Bisphenol a downregulates GLUT4 expression by activating aryl hydrocarbon receptor to exacerbate polycystic ovary syndrome

BackgroundBisphenol A (BPA) levels are high in women with polycystic ovary syndrome (PCOS). The mechanism by which BPA induces abnormal glucose metabolism in PCOS patients is largely unknown.MethodsSerum and urine samples were collected from women with and without PCOS (control) at the reproductive medicine center with informed consent. Non-PCOS patients who received in vitro fertilization were recruited for collection of ovarian follicular fluid and granular cells. Wild-type C57BL/6 and AhR−/− mice were used to verify the effects of BPA on PCOS. Real-time PCR, western blotting, and ELISA were conducted to analyze the function of BPA. Chip-qPCR verified the role of AhR in GLUT4 transcription. Flow cytometry was performed to determine glucose uptake.ResultsA positive correlation was observed between BPA concentration and serum BPA levels in PCOS patients. BPA aggravated the changes in PCOS with abnormal glucose metabolism, impaired fertility, and increased body fat. Mechanistically, we showed that BPA activated AhR and led to decreased glucose transport via GLUT4 downregulation in ovarian granular cells. Therefore, the use of inhibitors or knockout of AhR could effectively rescue BPA-induced metabolic disorders in PCOS mice.ConclusionsOur results revealed that BPA suppressed GLUT4 expression and induced abnormal glucose metabolism by activating AhR, causing insulin resistance, and is thus a potential contributor to the development of PCOS. Therefore, AhR could be a potential new therapeutic target for PCOS.Dp7QWqxpppdxU99YCnw6gzVideo

Effect of physiotherapy on infertility treatment in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a complex hormonal condition associated with psychological, reproductive, and metabolic features. Low-grade inflammation is a recognised factor causing metabolic and reproductive disorders in PCOS, which is why anti-inflammation approaches in PCOS treatment, especially during the COVID pandemic, are considered. A promising therapeutic option is osteopathic manipulative treatment (OMT), which activates the cholinergic anti-inflammatory pathway and can inhibit proinflammatory cytokines, such as TNF, IL-1β, and TNF-β. In our paper we analysed the influence of OMT in women with PCOS. Seventy-three patients, aged 29-46 years, with a history of reproductive failure, who underwent a physiotherapeutic treatment were evaluated. Six months after the end of a physiotherapy session, a follow-up questionnaire was performed. The results show that most women (83.6%) were satisfied with the therapeutic process, and that the sessions met the patient's expectations. Reducing the level of anxiety related to infertility treatment and pregnancy was declared by 60 (82.2%) women, an improvement in well-being was declared by 72 (97.3%) (p = 0.04), and increasing awareness of the body after physiotherapy sessions was declared by 70 (95.9%) women. The physiotherapeutic sessions improved infertility treatment, enhanced quality of life, and had a positive effect on overall health in PCOS women.

The Comparative Effect of Citrullus colocynthis Hydro-Alcoholic Extract and Metformin on Morphometric Ovarian Follicles Disorders in Estradilol valerate-Iinduced Polycystic Ovary Syndrome Rats

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6-10% of women in reproductive age. The medicinal values of Citrullus colocynthis extract (CCT) stems from its anti-oxidative and anti-inflammatory effects. This study evaluated the comparative effect of CCT and metformin on morphometric ovarian disorders in PCOS rats. Materials and Methods: Fifty female Wistar rats having 2-3 consecutive estrous cycles during two weeks were divided into five groups (n=10 each group). The rats in the control group only received sesame oil as estradiol valerate solvent, whereas the rats in the sham group were injected intramuscularly with 4 mg/rat estradiol valerate-induced PCOS. Following PCOS induction, the rats in the metformin group received 50 mg/kg metformin orally for three weeks. Rats in the Extract group were treated with 50 mg/kg plant extract for 21 days following the induction with PCOS. Additionally, the rats in metformin+ extract group were treated with the combination of 50 mg metformin plus plant extract for three weeks. The ovaries were removed and were fixed for tissue processing. The slices were stained by hematoxylin-eosin after clearing and hydration. Follicular count and morphometric changes were evaluated in primordial, primary, pre-antral and antral follicles. Results: The mean diameter of primordial follicle was similar in all groups, but mean diameter of primary follicle decreased in the sham group (145.50± 49.26 µm) compared to metformin (278.76± 156.64 µm), extract (311.70± 147.74 µm) and metformin+ extract groups (265.35± 88.16 µm). The diameter of pre-antral and antral follicles in the sham group were significantly larger than those in the control group, but were not significantly different in all other groups including metformin, extract, and metformin+ extract in comparison with control group (P< 0.05). Conclusion: In this study, the data has demonstrated that CCT like metformin could improve follicular morphometric disorders in PCOS rats. [GMJ.2018;7:e1045] Â

Disorders of carbohydrate metabolism and candidate genes for the pathophysiology of polycystic ovary syndrome. A literature review

Polycystic ovary syndrome is a common heterogeneous disease with metabolic disorders. In the last decade, the study of polycystic ovary syndrome pathogenesis has been associated with the modern development of molecular genetics, transcriptomics, and sequencing methods. Numerous studies have shown that the study of genetic markers and epigenetic changes in metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis and etiology of the disease. The aim of this literature review was to describe candidate genes involved in the pathophysiology of polycystic ovary syndrome and associated with disorders of carbohydrate metabolism according to modern domestic and foreign literature over the past five years. The candidate gene data presented were assessed based on the main aspects of polycystic ovary syndrome pathophysiology, namely, metabolic dysfunction, androgen and gonadotropin imbalance, and inflammation. The insulin genes (variable number of tandem repeats), such as INS-VNTR, IRS-1, IRS-2, and INSR, adiponectin and calpain-10 genes, as well as CY1A1, CYP11A1, PON1, DENND1A and TCF7L2 genes are associated with metabolic disorders in polycystic ovary syndrome. Genetic variants of genes involved in regulating the expression and mechanism of action of insulin, as well as its receptors and substrates (IRS-1, IRS-2, INSR), have been suggested as possible factors involved in the development and severity of the clinical and metabolic manifestations of polycystic ovary syndrome. The presented data on PPARγ gene (and its coactivator PGC-1α) expression levels in women with polycystic ovary syndrome revealed the presence of PPARγ gene polymorphisms associated with insulin resistance. Thus, the data presented in this review from genome-wide association studies (GWAS) and the study of candidate genes showed that numerous pleiotropic effects cause carbohydrate metabolism disorders in polycystic ovary syndrome. The study of genetic markers and epigenetic changes in the development of metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis of the disease.

Hepatokines: the missing link in the development of insulin resistance and hyperandrogenism in PCOS?

The liver plays a critical role in several metabolic pathways, including the regulation of glucose and lipid metabolism. Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, is closely associated with insulin resistance (IR) and metabolic syndrome (MetS). Hepatokines, newly discovered proteins secreted by hepatocytes, have been linked to the induction of these metabolic dysregulations. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, has been associated with NAFLD and IR, while hyperandrogenism additionally appears to be implicated in the pathogenesis of the latter. However, the potential role of hepatokines in the development of metabolic disorders in PCOS has not been fully investigated. Therefore, the aim of this review is to critically appraise the current evidence regarding the interplay of hepatokines with NAFLD, hyperandrogenism, and IR in PCOS.

Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority. Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32-1.52) for anxiety, 1.65 (95% CI: 1.44-1.89) for depression, 1.48 (95% CI: PR: 1.06-2.05) for eating disorders, and 1.20 (95% CI: 0.96-1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD. Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence.

Association Between Mental Health and Reproductive System Disorders in Women

Reproductive system and mental health disorders are commonly comorbid in women. Although the causes of this overlap remain elusive, evidence suggests potential shared environmental and genetic factors associated with risk. To investigate the comorbidity between psychiatric and reproductive system disorders, both as broad diagnostic categories and among specific pairs of diagnoses. PubMed. Observational studies published between January 1980 and December 2019 assessing prevalence of psychiatric disorders in women with reproductive system disorders and prevalence of reproductive system disorders in women with psychiatric disorders were included. The study did not include psychiatric and reproductive disorders triggered by life events (eg, trauma, infection, surgery) to address potential confounding. A search yielded 1197 records, of which 50 met the inclusion criteria for the qualitative and 31 for the quantitative synthesis in our study. A random-effects model was used for data synthesis and Egger test and I2 to assess study bias and heterogeneity. Data were analyzed from January to December 2022. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Psychiatric and reproductive system disorders. A total of 1197 records were identified, of which 50 met the inclusion criteria for qualitative and 31 for quantitative synthesis. Diagnosis of a reproductive system disorder was associated with a 2- to 3-fold increased odds of having a psychiatric disorder (lower bound odds ratio [OR], 2.00; 95% CI, 1.41-2.83; upper bound OR; 2.88; 95% CI, 2.21-3.76). The analysis focused on specific diagnoses described in the literature and found that polycystic ovary syndrome was associated with increased odds of depression (population-based studies OR, 1.71; 95% CI, 1.19-2.45; clinical studies OR, 2.58; 95% CI, 1.57-4.23) and anxiety (population-based studies OR, 1.69; 95% CI, 1.36-2.10; clinical studies OR, 2.85; 95% CI, 1.98-4.09). Chronic pelvic pain was also associated with both depression (OR, 3.91; 95% CI, 1.81-8.46) and anxiety (OR, 2.33; 95% CI, 1.33-4.08). Few studies investigated risk of other reproductive system disorders in women with psychiatric disorders, or reverse associations (risk of reproductive system disorder among women with a psychiatric diagnosis). In this systematic review and meta-analysis, a high rate of reported co-occurrence between psychiatric and reproductive disorders overall was observed. However, data for many disorder pairs were limited. The available literature focused overwhelmingly on affective disorders in polycystic ovary syndrome, overlooking a substantial portion of disease overlap. As such, the associations between the majority of mental health outcomes and conditions of the female reproductive system are largely unknown.

Effects of Mindfulness-Based Therapy on Clinical Symptoms and DNA Methylation in Patients with Polycystic Ovary Syndrome and High Metabolic Risk

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. Research has shown that epigenetic alterations such as DNA methylation may play a role in the development and progression of abnormal ovarian function and metabolic disorders in PCOS. Studies have identified specific genes (related with insulin signaling and steroid hormone metabolism) that are methylated in women with PCOS. DNA methylation appears to respond to various interventions aimed at altering health and lifestyle factors. We tested the efficacy of a mindfulness-based stress reduction program (MBSR) in PCOS patients. We examined its effects on anthropometric measurements, mental health and wellbeing, and alterations in DNA methylation in peripheral blood. MBSR was associated with a reduction in body mass index, waist circumference and blood glucose level, an improvement in subjectively perceived general health, emotional role limitation, and levels of pain, as well as mindfulness-like traits. MBSR reduced the expression of anxious symptomatology and subjectively perceived stress. Methylation changes were observed in four genes: COMT, FST, FKBP51, and MAOA. We conclude that MBSR may be a useful supplementary therapy to mitigate the deleterious effects of PCOS on mental health.

Carnosol inhibits KGN cells oxidative stress and apoptosis and attenuates polycystic ovary syndrome phenotypes in mice through Keap1-mediated Nrf2/HO-1 activation.

Excessive oxidative stress and apoptosis of ovarian granulosa cells lead to abnormal follicular development and ovulation disorders in polycystic ovary syndrome (PCOS). Carnosol is a plant-derived polyphenol that has been proven to exhibit several cell protective effects. In this study, we established hyperandrogenic PCOS models both in vitro and in vivo. In the humanovariangranulosacellline,KGN cells, decreased viability and mitochondrial membrane potential, and upregulated reactive oxygen species (ROS) level and apoptosis induced by DHT were partly reversed by carnosol. Western blotting results showed that carnosol treatment inhibited the DHT-activated mitochondrial apoptotic pathway by activating nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase 1 (HO-1). Knockdown of Nrf2 by transfecting with siRNA or inhibiting HO-1 by zinc protoporphyrin (ZnPP) blocked the protective effects of carnosol. Computational modeling and pull-down assay results confirmed the direct binding of carnosol to kelch-like ECH-associated protein 1 (Keap1). In vivo results showed that the intraperitoneal administration of carnosol (50 and 100 mg/kg) improved estrous cycle disorders, polycystic ovary, and decreased elevated androgen in the PCOS mice. In summary, Carnosol has an effective role in inhibiting oxidative stress and apoptosis in DHT-treated KGN cells and protecting against mouse PCOS phenotypes through the Keap1-mediated activation of Nrf2/HO-1 signaling.

Evening chronotype is associated with hormonal and metabolic disorders in polycystic ovary syndrome.

Despite current treatments for polycystic ovary syndrome (PCOS), a considerable number of women with this syndrome do not reach the treatment goal, suggesting the presence of other probable misdiagnosed features of this syndrome that are not taken into account in the assessment and therefore in the therapeutical approach. The aim of this study was to investigate the prevalence of chronotype categories in women with PCOS and their role in determining hormonal and metabolic aspects of PCOS.This observational case-control study was conducted on 112 women with PCOS and 112 healthy women matched for age and body mass index (BMI). At baseline anthropometric parameters such as weight, height, BMI and waist circumference, clinical parameters such as Ferriman-Gallwey (FG) score, biochemical parameters such as fasting plasma glucose, insulin levels and assessment of the homeostasis model of insulin resistance (HoMA-IR), inflammatory parameters such as C-reactive protein (CRP) and hormonal parameters such as testosterone levels were evaluated.Women with PCOS had a lower chronotype score (p < .001) which indicates a higher prevalence of evening chronotype (EC) category (p = .037) compared to controls. After adjustment for BMI, chronotype score was significantly negatively correlated with CRP levels (r = -0.418, p < .001), testosterone levels (r = -0.543, p < .001) and FG score (r = -0.514, p < .001). Linear regression analysis showed that high testosterone levels were among the factors most associated with a lower chronotype score (p < .001), followed by BMI (p < .001) and HoMA-IR (p < .05).In conclusion, there is a higher prevalence of EC in women with PCOS than in women without the condition, which in turn was associated with a worse hormonal and metabolic profile. These findings provide support for the relevance of including chronotype assessment in the treatment of women with PCOS.

RF10 | PMON218 Direct Costs of Mental Health Disorders in PCOS: Systematic Review and Meta-Analysis

Abstract BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent endocrine abnormality of reproductive-aged women today, affecting one in seven reproductive-aged women worldwide, and represents a significant financial burden to our health care. Women with PCOS have an increased risk for developing mental health (MH) disorders, in part due to biochemical changes, constant concerns regarding physical appearance, and social stigma from hirsutism, obesity, and infertility. OBJECTIVE: To determine the excess economic burden associated with MH disorders in women with PCOS. METHOD: Followed PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021 for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer-reviewed. As anxiety, depression, and eating disorders were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random-effects model (DerSimonian and Laird 1986) to compute pooled estimates of odds ratios (OR) for the associations between PCOS and anxiety, depression, and eating disorders. Study-specific and overall estimates using the log-odds scale were presented using forest plots. Between-study heterogeneity was evaluated using the I2 statistic. We then calculated the excess direct costs of these MH in U.S. dollars (USD) for women suffering from PCOS. RESULT: ​​We screened 72 articles by title/abstract, assessed 37 articles in full-text, and included 24 articles. Pooled ORs were 1.65 (95% CI: 1.15-2.38) for anxiety, 2.20 (95% CI: 1.69-2.86) for depression, and 2.53 (95% CI: 1.14-2.07) for eating disorders, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with MH disorders in PCOS were estimated to be $3.075 billion/yr., $2.280 billion/yr., and $0.714 billion/yr. in 2021 USD for depression, anxiety, and eating disorders, respectively. Taken together, the additional direct healthcare costs associated with these MH disorders in PCOS was estimated to be $6.069 billion/yr. in 2021 USD. CONCLUSION: This work is the first to estimate the excess direct healthcare costs of MH disorders associated with PCOS. Overall, the direct healthcare costs for the most common MH disorders in PCOS, namely depression, anxiety, and eating disorders, exceeded $6 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $14 billion yearly, considering the costs of diagnosis, and MH, reproductive, vascular, and metabolic disorders (but not indirect and intangible costs). As PCOS is a global disorder with much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. Presentation: Saturday, June 11, 2022 1:36 p.m. - 1:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Oxidative stress and antioxidant imbalance in ovulation disorder in patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that is characterized by oligo-ovulation or anovulation, hyperandrogenism, and polycystic ovaries observed using ultrasound with high clinical heterogeneity. At present, the etiology of PCOS is not clear but is thought to be related to genetic, metabolic, endocrine and environmental factors. Hyperandrogenism interacts with insulin resistance and overweight/obesity, forming a vicious cycle of mutual promotion and participating in the occurrence and progression of PCOS. Oxidative stress (OS) refers to the imbalance between the oxidation system and antioxidation system in the human body, which is associated with the occurrence and development of various diseases. Recent studies have shown that OS may be closely related to ovulation disorders in PCOS, and antioxidants can improve the oxidative stress state of PCOS. However, previous studies did not examine the effect of the interaction between OS and hyperandrogenism, insulin resistance or overweight/obesity on ovulation disorders in PCOS. This article reviews the interaction between OS and hyperandrogenism, insulin resistance and overweight/obesity; the effects of OS, hyperandrogenism, insulin resistance and overweight/obesity on ovulation disorders in PCOS; and the application of antioxidants in PCOS.

Assessment of Neuregulin4 function in patients with polycystic ovary syndrome disorder

Subject: Polycystic ovary syndrome (PCOS) is female disorder caused by cysts formation in ovarian that results disorder of hormones secretion and menstrual cycle. Neuregulin 4 (NRG4) is one of adipokines family members synthesis and release via adipose tissues, it acts as activator the epidermal growth factor receptor (EGFR).Objective of the Study: Assessment role of NRG4 in PCOS patients.Materials and Methods: Present study included 30 PCOS patients with 30 controls, the age individuals of tow group at study were 18 years and above of females. At this study measured serum NRG4 level by quantity method for all study individuals, the body mass index (BMI) also measured for all study individuals.Results: Present study explain increase of NRG4 level in serum samples and BMI in PCOS patients group compared with control group.Conclusion: Current study demonstrate role of NRG4 level that act as compensate mechanism in PCOS disorder.

Not only diet quality and physical activity but also snacking and skipping meals could be related with menstrual disorders in PCOS

ABSTRACT The aim of this study was to clarify the associations between menstrual cycle disorders, food frequency intake, dietary habits, and physical activity levels in women with and without Polycystic Ovary Syndrome (PCOS). 114 women with PCOS and 341 without PCOS (CONTROL) participated in the study. They were also divided into women with menstrual disorders(MD), and those with regular cycle (RC). Each of them completed a medical and Kompan questionnaires. In women with PCOS and menstrual disorders (PCOS-MD), intake of wholemeal products, meat and meat products, fats and alcoholic beverages was higher in comparison to those in the control group with menstrual disorders (CONTROL-MD). Women in the PCOS-MD group also reported significantly more frequent snacking between meals, higher Pro-Healthy Diet Index (pHDI-14), and a lower level of physical activity at leisure time than CONTROL-MD. Women with PCOS differed from those in CONTROL due to a higher consumption of meat and meat products, fats, fruits and vegetables, juices and alcoholic beverages, and a lower intake of whitemeal products, sweets, and fruits. Women with PCOS more frequently snacked, but the number of their meals was also lower. In women with PCOS, menstrual disorders may be related not only with diet quality and physical activity but also with snacking and skipping meals.

Sex Steroid Receptors in Polycystic Ovary Syndrome and Endometriosis: Insights from Laboratory Studies to Clinical Trials.

Polycystic ovary syndrome (PCOS) and endometriosis are reproductive disorders that may cause infertility. The pathology of both diseases has been suggested to be associated with sex steroid hormone receptors, including oestrogen receptors (ER), progesterone receptors (PRs) and androgen receptors (ARs). Therefore, with this review, we aim to provide an update on the available knowledge of these receptors and how their interactions contribute to the pathogenesis of PCOS and endometriosis. One of the main PCOS-related medical conditions is abnormal folliculogenesis, which is associated with the downregulation of ER and AR expression in the ovaries. In addition, metabolic disorders in PCOS are caused by dysregulation of sex steroid hormone receptor expression. Furthermore, endometriosis is related to the upregulation of ER and the downregulation of PR expression. These receptors may serve as therapeutic targets for the treatment of PCOS-related disorders and endometriosis, considering their pathophysiological roles. Receptor agonists may be applied to increase the expression of a specific receptor and treat endometriosis or metabolic disorders. In contrast, receptor antagonist functions to reduce receptor expression and can be used to treat endometriosis and induce ovulation. Understanding PCOS and the pathological roles of endometriosis sex steroid receptors is crucial for developing potential therapeutic strategies to treat infertility in both conditions. Therefore, research should be continued to fill the knowledge gap regarding the subject.

Regulatory Role and Potential Importance of GDF-8 in Ovarian Reproductive Activity.

Growth differentiation factor-8 (GDF-8) is a member of the transforming growth factor-beta superfamily. Studies in vitro and in vivo have shown GDF-8 to be involved in the physiology and pathology of ovarian reproductive functions. In vitro experiments using a granulosa-cell model have demonstrated steroidogenesis, gonadotrophin responsiveness, glucose metabolism, cell proliferation as well as expression of lysyl oxidase and pentraxin 3 to be regulated by GDF-8 via the mothers against decapentaplegic homolog signaling pathway. Clinical data have shown that GDF-8 is expressed widely in the human ovary and has high expression in serum of obese women with polycystic ovary syndrome. GDF-8 expression in serum changes dynamically in patients undergoing controlled ovarian hyperstimulation. GDF-8 expression in serum and follicular fluid is correlated with the ovarian response and pregnancy outcome during in vitro fertilization. Blocking the GDF-8 signaling pathway is a potential therapeutic for ovarian hyperstimulation syndrome and ovulation disorders in polycystic ovary syndrome. GDF-8 has a regulatory role and potential importance in ovarian reproductive activity and may be involved in folliculogenesis, ovulation, and early embryo implantation.

Evening chronotype is associated with hormonal and metabolic disorders in Polycystic Ovary Syndrome

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)