Metabolic Disorders In Polycystic Ovary Syndrome Research Articles

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.

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

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.

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.

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.

DLK1 and Nesfatin-1 levels and the relationship with metabolic parameters in polycystic ovary syndrome: Prospective, controlled study

Objective:Delta-like 1 (DLK1) is known to inhibit adipocyte differentiation and nesfatin-1 is a neuropeptide that plays a role in the regulation of nutrition and metabolism. We aimed to assess both the levels of DLK1 and nesfatin-1 in polycystic ovary syndrome (PCOS) and determine the association of DLK1 and nesfatin-1 with metabolic parameters.Materials and Methods:Forty-four patients with PCOS and 40 healthy women as the control group were included in this study. Venous blood samples of the participants were collected, and hormonal, metabolic parameters, DLK1 and nesfatin-1 blood levels were determined. Anthropometric parameters were also determined. For a double comparison, the Mann-Whitney U test was used for non-parametric numerical data, and Student’s t-test was used for parametric numerical data. Bivariate correlations were investigated using Spearman’s correlation analysis. The diagnostic performance of the parameters was evaluated using receiver operating characteristic curve analysis.Results:The findings showed that DLK1 and nesfatin-1 levels were lower among the PCOS group, and the differences in these values were found to be statistically significant. A significant negative correlation was found between DLK1 levels and body mass index (BMI), waist/hip ratio, visceral adiposity index (VAI), fasting serum insulin (FSI), homeostasis model of assessment-insulin resistance (HOMA-IR) and triglyceride levels. A significant negative correlation was found between nesfatin-1 levels and BMI, VAI, FSI, HOMA-IR and triglyceride.Conclusion:The findings showed that DLK1 and nesfatin-1 levels were lower in PCOS. Based on this study, DLK1 may be culpable for metabolic disorders in PCOS and can be a novel marker for PCOS in the future.

Aberrant elevation of GDF8 impairs granulosa cell glucose metabolism via upregulating SERPINE1 expression in patients with PCOS

Clinical investigations have demonstrated that polycystic ovary syndrome (PCOS) is often accompanied by insulin resistance (IR) in more than 70% of women with PCOS. However, the etiology of PCOS with IR remains to be characterized. Growth differentiation factor 8 (GDF8) is an intraovarian factor that plays a vital role in the regulation of follicle development and ovulation. Previous studies have reported that GDF8 is a pathogenic factor in glucose metabolism disorder in IR patients. To date, the role of GDF8 on glucose metabolism of granulosa cell in PCOS patients remains to be determined. In the current study, we demonstrated that the expression and accumulation of GDF8 in human granulosa-lutein (hGL) cells and follicular fluid from PCOS patients were higher compared with those of non-PCOS women. GDF8 treatment caused glucose metabolism defects in hGL cells. Transcriptome sequencing results showed that SERPINE1 mediated GDF8-induced impairment of hGL glucose metabolism defects. Using pharmacological and small interfering RNA (siRNA)-mediated knockdown approaches, we demonstrated that GDF8 upregulated the expression of SERPINE1 via the ALK5-mediated SMAD2/3-SMAD4 signaling pathway. Interestingly, the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway was also activated with GDF8 treatment but did not participate in the effect of GDF8 on SERPINE1 expression. Our results also showed that TP53 was required for the GDF8-stimulated increase in SERPINE1 expression. Importantly, our study demonstrated that SB-431542 treatment significantly improved DHEA-induced PCOS-like ovaries. These findings support a potential role for GDF8 in metabolic disorders in PCOS.

Особенности лечения пациенток с синдромом поликистозных яичников и метаболическим синдромом

This paper discusses polycystic ovary syndrome (PCOS), a common endocrine disorder characterized by hirsutism, anovulation, and polycystic ovaries. Insulin resistance which is considered the major causative factor for both PCOS and metabolic syndrome is emphasized. The early diagnosis of metabolic disorders which increase the risk of cardiovascular complications and the complications of pregnancy (including gestational diabetes and hypertension which may result in preeclampsia and placental abruption) is of particular importance. The presence of metabolic syndrome in PCOS is associated with poor prognosis in terms of fertility and has a negative impact on the outcomes of in vitro fertilization in infertile women with PCOS. When describing treatment approaches, the role of metformin, inositol, folates, vitamin D, and statins in treating metabolic disorders in PCOS and metabolic syndrome, reducing the risks of cardiovascular complications, and realizing fertile function is highlighted. The course of PCOS is complicated by psychic disorders (i.e., depression, anxiety, bipolar disorder, or eating disorders) which are common in these women and should be considered when prescribing medications. KEYWORDS: polycystic ovary syndrome, insulin resistance, infertility, metabolic syndrome, cardiovascular complications, inositol, folates. FOR CITATION: Il’ina I.Yu. Specificities of the treatment for polycystic ovary syndrome and metabolic syndrome. Russian Journal of Woman and Child Health. 2020;3(4):254–259. DOI: 10.32364/2618-8430-2020-3-4-254-259.

A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study.

Polycystic ovary syndrome (PCOS) represents a serious reproductive and endocrine condition and is associated with high incidence rates. H19 is a compelling long noncoding RNA (lncRNA) which carries out a range of biological functions. However, prior to this study, little was known as to whether there was an association between lncRNA H19 and PCOS. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine lncRNA H19 expression levels in peripheral blood leukocytes from patients with PCOS and compared this data with that derived from normal controls. We also screened data for potential relationships between lncRNA H19 and a range of endocrine variables in PCOS. The expression of lncRNA H19 was significantly higher in cases of PCOS than in controls. Individuals exhibiting higher expression levels of lncRNA H19 were associated with a significantly higher risk of PCOS than those with lower expression levels. Moreover, lncRNA H19 expression was positively correlated with fasting plasma glucose levels; this was the case with both raw data, and after adjustment for age and BMI in the PCOS group. However, lncRNA H19 expression showed no significant correlation with total testosterone or insulin resistance in either PCOS cases or the controls. In conclusion, we demonstrate the first evidence to indicate that lncRNA H19 is associated with PCOS, suggesting that elevated lncRNA H19 levels are a risk factor for PCOS. For susceptible individuals, lncRNA H19 may represent a useful biomarker of the early stages of endocrine and metabolic disorders in PCOS.

Vitamin D-deficiency states in the genesis of woman reproductive health disorders

Thanks to the continuous scientific and creative search for researchers over the past almost hundred years, vitamin D preparations are finding increasing uses, from classical prevention of rickets and osteomalacia to the prevention of malignant neoplasms and mental illnesses. The article discusses the use of vitamin D in the genesis of women reproductive health disorders, as well as its impact on the condition of women in different periods - childhood, the age of menarche and adolescence, the reproductive age and the menopause. The influence of vitamin D deficiency on a number of diseases, in particular, inflammatory diseases of the pelvic organs, breast pathology, hyperproliferative diseases is considered in detail. The results of authors’ study, which confirms the normalization of vitamin D levels in patients who received the drug containing cholecalciferol, are indicative of its effectiveness in correcting vitamin D deficiency. As the authors of the article emphasize, encouraging patients to use preparations containing vitamin D and annual testing for D-status detection has the potential to become a modern method of preventing uterine fibroids, endometrial and breast cancer, obesity, and polycystic ovary syndrome (PCOS). Nutritional supplements and medicines containing cholecalciferol, which is the least toxic fat-soluble vitamin, with regular intake reduce the risk of progression of metabolic disorders in PCOS, promote the proper formation of pelvic bones in girls, prevent the development of postpartum depression and slow the aging and cognitive decline with age, quality of life in general. It is advisable to test for vitamin D (25(OH)D3) serum levels in a number of population categories, in particular, for women planning pregnancy, pregnant women and women with hyperproliferative diseases. When vitamin D deficiency is detected, it is necessary to use preparations containing cholecalciferol, with dosage depending on body weight and vitamin D content in the blood serum.

PCOS: phenotypes, visceral obesity and a personalized approach in the prescription of COC

Polycystic ovary syndrome (PCOS) is a complex of endocrine disease with several phenotypes, which determines the difficulties in its diagnostics (“diagnosis of exceptions”). This is an interdisciplinary disease, as the consequences of this syndrome can be serious (infertility, cardiovascular diseases, diabetes mellitus and their complications). The reason for this is the fact that PCOS occurs with metabolic disorders, manifested as violations of carbohydrate and fat metabolism.Determination of specific phenotypes of women with PCOS are justified from the point of metabolism. Metabolic disorders in PCOS can prevail throughout life. At the initial stages, these changes may be invisible and not diagnosed. PCOS is often characterized by the presence of insulin resistance and is associated with hyperinsulinemia in most obese patients.PCOS can occur with various forms of obesity, the most important is visceral obesity. This connected with the fact that visceral obesity may present in women with PCOS with no elevated body mass index. Therefore, timely diagnostics of obesity, especially visceral, determines the health consequences of this syndrome.There are certain difficulties in the diagnostics of visceral obesity, but many of them are surmountable in modern conditions. Women with PCOS need the use combined oral contraceptives with both contraceptive and curative purposes. Therefore, the choice of the medicine depending on the clinical situation, the peculiarities of redistribution of adipose tissue is important in clinical practice. With the correct choice of COC, there will be no significant adverse effects on the metabolic profile of patients with PCOS and, possibly, a positive effect on their lipid profile will be observed. And yet, weight loss can lead to spontaneous ovulation in women with PCOS and overweight or obese, so the first choice in treatment of such patients should be diet and lifestyle changes, including an increase of daily physical activity.

Oxidative stress in the syndrome of polycystic ovaries: prognostic value, correction possibilities

Polycystic ovary syndrome (PCOS) is a widespread multifactorial endocrine pathology, which includes both reproductive system disorders and non-reproductive disorders. Among the links in the pathogenesis of metabolic disorders in PCOS, the so-called mitochondrial dysfunction plays an important role, which has a close connection with the formation of oxidative stress. In this regard, the markers of the oxidative stress should be used in the complex diagnosis of PCOS and associated complications. The use of antioxidants in complex correction and prevention of disorders accompanying this syndrome deserves special attention.

Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and endocrine metabolic disorders in PCOS.

Reduced Estradiol-Induced Vasodilation and Poly-(ADP-Ribose) Polymerase (PARP) Activity in the Aortas of Rats with Experimental Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

More attention should be paid to metabolic disorders in polycystic ovary syndrome

The prevalence of polycystic ovary syndrome (PCOS) in fertile aged women is about 6%. Many studies show that insulin resistance in PCOS is closely associated with metabolic disorders, which may even potentially increases the risk for cardiovascular diseases. Therefore, metabolic disorders in PCOS should be controlled more actively. Key words: Polycystic ovary syndrome; Metabolic disorders; Insulin resistance