Features Of Polycystic Ovary Syndrome Research Articles

Investigating GABA neuron-specific androgen receptor knockout in two hyperandrogenic models of PCOS.

Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signalling in GABAergic neurons is critical in PCOS pathogenesis in two well-characterised hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic periperpubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to GnRH neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy and impaired glucose homeostasis, was not different between GABARKO and WT mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinising hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signalling in GABA neurons is largely not required for the development of PCOS-like traits in androgenised models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signalling in GABA neurons.

Interleukin-6/Glycoprotein130 Signaling Inhibition Ameliorates Renal Mitochondrial Dysfunction And Associated Renal Injury In Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and polycystic ovaries. Renal injury, increased central adiposity, and chronic low-grade systemic inflammation are common characteristics of PCOS. Renal inflammation can induce mitochondrial dysfunction, which plays a pivotal role in renal pathophysiology and chronic kidney disease progression. Interleukin-6 (IL-6) is a key inflammatory cytokine that is involved in renal injury progression by activating its soluble receptor (sIL-6R) and a membrane-bound glycoprotein130 (gp130). Serum IL-6 levels are elevated in women with PCOS; however, its role in inducing renal mitochondrial dysfunction and consequently PCOS-mediated renal injury is unknown. Therefore, we aimed to test the hypothesis that hyperandrogenemia increases systemic and renal IL-6 levels, leading to the activation of IL-6/gp130 signaling, which in turn triggers intrarenal mitochondrial dysfunction and renal injury in a well-characterized mouse model of PCOS. Methods: Three-week-old peripubertal female mice were implanted with Silastic tubes filled with the non-aromatizable androgen dihydrotestosterone (DHT, 8 mg) or vehicle for 12 weeks. Eight weeks post-Silastic tubes implantation, the animals were treated with the IL-6/gp130 signaling inhibitor SC144 (10 mg/kg, SC, 3x/week) or its vehicle for 4 weeks. Body weight (gravimetry), fat mass (EchoMRI), kidney weight (gravimetry), serum IL-6 (Bioplex), glomerular filtration rate (GFR, transcutaneous fluorescence), as well as the renal injury markers urinary albumin to creatinine ratio (UACR, clinical chemistry analyzer), and NGAL (ELISA) were assessed. Renal gp130 protein and IL-6 mRNA expression were quantified by Western blot and RT-qPCR, respectively. The mitochondrial markers cytochrome C, succinate dehydrogenase A (SDHA), the mitochondrial stress protein HSP60, and voltage-dependent anion channel (VDAC) were assessed in the renal tissue by Western blot. H&E stained renal sections were used for histopathological analysis. Freshly isolated kidney mitochondria were used to measure mitochondrial reactive oxygen species (mtROS) by Amplex Red assay. Moreover, mitochondrial complex I and complex II-driven respiration along with complex IV activity were assessed using Oroboros Fluorespirometer. Results: DHT significantly (p<0.05) increased body weight (26.2±0.9 vs. 22.23±0.4 g), fat mass (3.2±0.4 vs. 1.9±0.4 g), kidney weight (365.6 ± 13.1 vs. 257.1 ± 3.7 mg), UACR (1,227±420 vs. 404±169 μg albumin/mg creatinine), urinary NGAL (2-fold), and serum IL-6 levels (2.2-fold). Additionally, DHT increased the expression of renal gp130 and IL-6 (1.5-fold) and decreased GFR (1067.2 ± 59.9 vs. 1335.6 ± 60.3 uL/min/100g body weight). Moreover, cytochrome c levels in PCOS mice were significantly lower (32%), while HSP60 levels were higher (4-fold). The latter changes were associated with higher mtROS generation (2-fold), as well as lower complexes I, II, III, and IV respiration (43-71%). PCOS mice also showed a worsen renal histological structure with congested glomeruli, exfoliation of luminal epithelial lining, and interstitial hemorrhage. SC144 therapy had no effect on kidney weight or GFR; however, it abolished DHT-induced increases in body weight and fat mass. Excitingly, SC144 treatment normalized the levels of UACR, and decreased both glomerular and tubular injury in PCOS mice. It also decreased renal HSP60 levels and mtROS generation and increased complex IV derived respiration. Conclusion and significance: Our findings suggest that IL-6/gp130 activation plays a significant role in renal outcomes in PCOS. Targeting IL-6 signaling could be a novel therapeutic approach to ameliorate renal injury in PCOS women. Supported by NIH grants NIGMS P20GM121334 to KSE, LLYC, and DGR; NIH-NIGMS P30GM149404 to SR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

<i>In Silico</i> Screening of a Phytochemical Naringin, Isolated from <i>Citrus decumana</i> var. <i>paradisi</i> Against the Genes of Polycystic Ovary Syndromenes of Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is a complex hormonal and metabolic disorder. The overproduction of androgens is the primary feature of PCOS. The currently available pharmacological agents recommended for the treatment of PCOS are linked with several adverse effects. Therefore, herbal-based drugs with lesser side effects, have become a favourable trend among people. A flavonoid glycoside, naringin isolated from different fruit parts of Citrus decumana var. paradisi (Macfad.) H.H.A. Nicholls exhibits a wide range of therapeutic properties. In the traditional system of medicine, it is used to improve ovarian health. To set down scientific evidence, molecular docking analysis was performed to find out the binding affinity of compound naringin with the protein CYP 17-cytochrome P 450, attributing to hyperandrogenism due to its overexpression, leading to PCOS. The docking score values were compared with the standard drug metformin to interpret the effectiveness of flavonoid naringin in the treatment of PCOS.

Use of nutraceuticals and micronutrient supplementation for the management of Polycystic Ovary Syndrome: a scoping review

Polycystic Ovary Syndrome (PCOS) is a common hormonal condition affecting women of reproductive age(1). Women with PCOS experience a broad range of clinical symptoms, collectively grouped into reproductive, metabolic, psychological and anthropometric features(2). Complementary therapies, such as nutrient supplementation, have been identified as potential adjunct therapeutic approaches to support currently recommended lifestyle and pharmacological interventions(3). However, evidence for their overall efficacy and safety is inconsistent and unclear. This review aimed to systematically map the available literature on the use of nutrient supplementation for the management of PCOS features, including metabolic, reproductive, psychological and anthropometric. This review followed a systematic approach with literature searches using CINHAL, Cochrane reviews, Medline, PsycINFO, Scopus and LILACS conducted up to April 2022. All types of study designs were included if they reported on the efficacy or association between micronutrient supplementation and/or nutraceuticals on features of PCOS in women (≥ 18 years) with a confirmed diagnosis of PCOS. A total of 317 articles were included involving n = 23,926 women. Forty-three different supplements examined various clinical features of PCOS grouped into metabolic, reproductive, psychological and anthropometric. The most studied supplements included Inositols (n = 83), Vitamin D (n = 51), N-acetylcysteine (n = 25), Omega-3 fatty acids (n = 18) and Biotics (n = 14). Most studies (n = 262; 83%) reported on reproductive features followed by metabolic (n = 212; 66%), anthropometric (n = 181; 57%) and psychological (n = 5; 2%). Less than half (n = 148; 47%) of the included studies reported on the potential for adverse events. Our results highlight that the potential therapeutic benefit of micronutrient and nutraceutical supplementation on psychological features of PCOS warrants future exploration. Additional primary studies that are adequately powered are needed to investigate therapeutic doses needed for clinical benefits. Lastly, a more rigorous approach to monitoring and recording adverse event data is recommended.

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.

Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. This is a retrospective study, and subjects attended for care from 2004 to 2022. Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. We could not evaluate hormonal or ultrasound parameters in controls. Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. No funding was received in support of this study. The authors have no conflicts of interest to disclose. N/A.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Experimental animal models for polycystic ovarian syndrome (methods, effects, and implications)

&lt;p class="MDPI17abstract"&gt;Many studies have replicated the clinical and genetic features of polycystic ovarian syndrome (PCOS) using a range of experimental animal models to improve treatment outcomes. This article aims to present an overview of the various experimental animal models that have been used in PCOS research. In this study, we conducted a systematic review of relevant research articles on the induced animal model PCOS. We searched research articles in Indonesian and English published over the last five years through three databases: PubMed, ScienceDirect, Google Scholar. We use established inclusion and exclusion criteria to select suitable articles. Out of 19 research articles included in our systematic review, we found the animal model PCOS based Rotterdam criteria, PCOS-IR model, PCOS-Inflammation model, PCOS-Gut microbiota model and PCOS-syndrome metabolic model. Androgen agents such as testosterone propionate, free testosterone, DHEA, and letrozole, as well as sodium valproate, are effective in the induction of PCOS phenotypes based on the Rotterdam criteria (oligo/amenorrhea, hyperandrogenic, and polycystic ovaries).&lt;/p&gt;

BMI and Polycystic Ovary Syndrome: Demographic Trends in Weight and Health.

Introduction Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in adolescence and reproductive age. The distribution of PCOS across different body mass index (BMI) categories can vary, and research has shown associations between PCOS and weight status. This study tries to evaluate the distribution of PCOS in relation to BMI in women attending the PCOS clinic in a tertiary hospital in eastern India. Methodology This hospital-based cross-sectional study was carried out in the gynecology outpatient departmentof a tertiary care center. The study population included all the women in the age group between 15 and 45 years diagnosed as having PCOSusing the Rotterdam definition. The various physical, clinical, and biochemical parameters were measured in the study population and compared among the obese and lean PCOS patients. Results and discussion A total of 143 women were included in the study. The mean age of the study population was 26.8 years. Among these, the underweight and normal weight patients were categorized as lean PCOS patients, 35 in number (24.5%), and overweight and obese patients were categorized as obese PCOS patients, 108 in number (75.5%). All the physical parametermeasures like age (mean = 28.05, SD = 5.722), height (mean = 153.384, SD = 6.679), weight (mean = 68.182, SD = 11.501), waist circumference (mean = 95.135, SD = 10.291), hip circumference (mean = 101.47, SD = 9.320), waist-to-hip ratio (mean = 0.940, SD = 0.0831), and neck circumference (mean = 34.85, SD = 2.445) were significantly higher in the obese group as compared to the lean group. Menstrual irregularity was significantly more common in the obese PCOS patients as compared to the lean PCOS group (p = 0.02). There was a significant difference (p < 0.05) between the obese and lean PCOS patients when the biochemical parameters like fasting insulin, fasting glucose, and homeostatic model assessment of insulin resistance (HOMA-IR) were compared. There is a strong link between obesity, insulin resistance, and PCOS. Obesity can exacerbate insulin resistance, a common feature of PCOS, leading to increased levels of insulin and androgens. Conclusion The demographic distribution of PCOS in relation to BMI is essential for tailoring interventions and treatments.

Polycystic Ovary Syndrome and Irritable Bowel Syndrome: Is There a Common Pathway?

Little is known about how polycystic ovary syndrome (PCOS) is linked to irritable bowel syndrome (IBS). This study aimed to review the existing literature regarding the association between PCOS or its symptoms and complications with IBS. In this review, studies that investigated the proposed cross-link between features of PCOS and IBS were included. This review collectively focused on recent findings on the mechanism and novel insight regarding the association between IBS and PCOS in future clinical practice. An electronic search of PubMed, Scopus, Epistemonikos, Cochrane Library and Google Scholar was performed. We did not restrict the study setting and publication date. The existing evidence has not completely answered the question of whether there is an association between PCOS and IBS and vice versa. Six case-control studies (793 women with PCOS and 547 women in the control group) directly assessed the association between PCOS and IBS. The prevalence of IBS among women with PCOS in these studies has ranged from 10% to 52% compared with 5%-50% in control groups. Evidence suggested the common pathways may have contributed to the interaction between IBS and PCOS, including metabolic syndrome, sex hormone fluctuation, dysregulation of neurotransmitters, psychological problems and environmental and lifestyle factors. To date, it is still ambiguous which of the mentioned components largely contributes to the pathogenesis of both. Although limited evidence has shown a higher prevalence of IBS in women with PCOS, there are several potential, direct and common indirect pathways contributing to the development of both IBS and PCOS.

Systematic Review on the Various Clinical Features of Polycystic Ovary Syndrome (PCOS) Patients

Systematic Review on the Various Clinical Features of Polycystic Ovary Syndrome (PCOS) Patients

BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response

Abnormal autophagy is one of the vital features in polycystic ovary syndrome (PCOS). However, the underlying molecular mechanisms remain unelucidated. In this study, we aimed to investigate whether Block of Proliferation 1 (BOP1) is involved in the onset of autophagy activation of granulosa cells in PCOS. Firstly, we found that BOP1 expression was significantly down-regulated in the ovaries of PCOS mice, which was associated with the development of PCOS. Next, local injection of lentiviral vectors in the ovary for the overexpression of BOP1 significantly alleviated the phenotypes of elevated androgens, disturbed estrous cycle, and abnormal follicular development in PCOS mice. Subsequently, we found that knockdown of BOP1 activated autophagy of granulosa cells in the in vitro experiments, whereas overexpression of BOP1 inhibited autophagy in both in vivo and in vitro models. Mechanistically, BOP1 knockdown triggered the nucleolus stress response, which caused RPL11 to be released from the nucleolus into the nucleoplasm and inhibited the E3 ubiquitination ligase of MDM2, thereby enhancing the stability of p53. Subsequently, P53 inhibited mTOR, thereby activating autophagy in granulosa cells. In addition, the mRNA level of BOP1 was negatively correlated with antral follicle count (AFC), body–mass index (BMI), serum androgen levels, and anti-Mullerian hormone (AMH) in patients with PCOS. In summary, our study demonstrates that BOP1 downregulation inhibits mTOR phosphorylation through activation of the p53-dependent nucleolus stress response, which subsequently contributes to aberrant autophagy in granulosa cells, revealing that BOP1 may be a key target for probing the mechanisms of PCOS.

Gonadal dysfunction in women with diabetes mellitus.

It is well known that both type 1 and type 2 diabetes mellitus (DM) are related to increased risk for cardiovascular (CV) and chronic kidney disease (CKD). However, besides these prominently presented complications, DM has also been associated with reproductive dysfunctions. It seems that these disorders are met in up to 40% of women with DM and consist of delayed menarche, all types of menstrual disorders, such as amenorrhea, oligomenorrhea, menstrual irregularity, as well as menorrhagia, infertility, characteristics of polycystic ovary syndrome (PCOS) and early (or rarely late) menopause. In type 1 DM (T1DM), insulin treatment, although it has reduced the rates of insulinopenic-induced hypogonadotropic hypogonadism, an entity commonly presented in many women with the disease in the past decades, when it is used in excess it can also promote hyperandrogenism. Regarding type 2 DM (T2DM), insulin resistance (IR) and hyperinsulinemia have mainly been implicated in the pathogenesis of reproductive dysfunctions, as insulin can act as gonadotropin on the theca cells of the ovary and can lead to hyperandrogenism and inhibition of proper ovulation. This review aims to detail the reproductive dysfunctions associated with DM and provide scientific data to enlighten the underlying pathogenetic mechanisms.

Androgen receptor actions on AgRP neurons are not a major cause of reproductive and metabolic impairments in peripubertally androgenized mice.

Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron-specific androgen receptor knockout alleviates some PCOS-like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti-related peptide (AgRP)-expressing neurons, which are important for both reproductive and metabolic function. We used a well-characterised peripubertal androgenized mouse model and Cre-loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co-expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT-induced androgen-induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons.

Exploring the physiological factors relating to energy balance in women with polycystic ovary syndrome: a scoping review.

Polycystic ovary syndrome (PCOS) occurs in 8%-13% of reproductive-aged women and is associated with reproductive, metabolic, and psychological dysfunction. Overweight and obesity are prevalent and exacerbate the features of PCOS. The aim of this review is to evaluate the extent of evidence examining the physiological factors affecting energy homeostasis, which may impact weight gain, weight loss, and weight maintenance in PCOS, and identify research gaps and recommendations for future research. Literature searches using MEDLINE, EMBASE, PsycInfo, AMED, CINAHL, and Cochrane Central Register of Controlled Trials were conducted up to June 22, 2022. Abstracts, non-English-language articles, and reviews were excluded. A total of n = 78 (n = 55 energy intake and n = 23 energy expenditure) primary research papers were included. Papers with multiple outcomes of interest were counted as separate studies. Energy-intake studies (n = 89) focussed on assessing food, nutrient, or supplements stimuli and were grouped into the outcomes of gastrointestinal appetite hormones (n = 43), adipokines (n = 34), subjective appetite (n = 9), functional brain imaging (n = 3), and neuropeptides (n = 0). Energy-expenditure studies (n = 29) were grouped into total energy expenditure (n = 1), resting energy expenditure (n = 15), meal-induced thermogenesis (n = 3), nutrient oxidation (n = 5), and metabolic flexibility (n = 5). Across both energy-intake and -expenditure papers, 60% of the studies compared outcome responses in women with PCOS with a control group. Results were inconsistent, with 57% reporting no differences and 43% reporting altered responses in PCOS compared with controls, including blunted appetite hormone responses, metabolic inflexibility, and reduced energy expenditure. The authors identified that there is inconsistent, yet preliminary, evidence of possible altered physiological factors, which may impact energy balance and weight management. Further work is needed to act on the identified clinical and research gaps to support women with PCOS and health professionals in informing and achieving realistic weight-management goals for women with PCOS. Systematic Review Registration: The protocol was prospectively registered on the Open Science Framework on February 16, 2021 (https://osf.io/9jnsm).

Investigating the causal impact of polycystic ovary syndrome on gestational diabetes mellitus: a two-sample Mendelian randomization study.

Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM. The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome. The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method. We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS.

Insights From Liquid Chromatography-Mass Spectrometry-Measured Androgens in Indian Women With Polycystic Ovary Syndrome.

Hyperandrogenemia is the defining feature of polycystic ovary syndrome (PCOS). Increasingly androgens are being advocated to be measured through liquid chromatography-mass spectrometry (LC-MS/MS). The role of LC-MS/MS over immunoassay in diagnosis of PCOS has been debated over a long time. We analyzed the role of androgens as measured by LC-MS/MS in diagnosing women with PCOS. We performed a prospective case-control study involving 59 women with PCOS compared with 30 age- and BMI-matched controls. In PCOS phenotypes A-C (hyperandrogenic by definition), 19/47 (40%) had normal testosterone (T) levels but 14/19 (75%) had either elevated androstenedione (A4) or dehydroepiandrosterone. A4 had the highest area under curve (0.89) for diagnosing PCOS followed by T (0.81). Even in the PCOS-D phenotype (sonologic polycystic ovaries + oligomenorrhoea), A4 was significantly higher as compared to controls though still in normal range. A4 had arole in diagnosing hyperandrogenism in women with PCOS. Further studies clarifying the role of androgen profiles in diagnosing PCOS and its cost-effectiveness may be required in the future.

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.

Polycystic ovary syndrome and its management: In view of oxidative stress.

In the past two decades, oxidative stress (OS) has drawn a lot of interest due to the revelation that individuals with many persistent disorders including diabetes, polycystic ovarian syndrome (PCOS), cardiovascular, and other disorders often have aberrant oxidation statuses. OS has a close interplay with PCOS features such as insulin resistance, hyperandrogenism, and chronic inflammation; there is a belief that OS might contribute to the development of PCOS. PCOS is currently recognized as not only one of the most prevalent endocrine disorders but also a significant contributor to female infertility, affecting a considerable proportion of women globally. Therefore, the understanding of the relationship between OS and PCOS is crucial to the development of therapeutic and preventive strategies for PCOS. Moreover, the mechanistic study of intracellular reactive oxygen species/ reactive nitrogen species formation and its possible interaction with women's reproductive health is required, which includes complex enzymatic and non-enzymatic antioxidant systems. Apart from that, our current review includes possible regulation of the pathogenesis of OS. A change in lifestyle, including physical activity, various supplements that boost antioxidant levels, particularly vitamins, and the usage of medicinal herbs, is thought to be the best way to combat this occurrence of OS and improve the pathophysiologic conditions associated with PCOS.

Targeted deletion of NR2F2 and VCAM1 in theca cells impacts ovarian follicular development: insights into polycystic ovary syndrome?†.

Defining features of polycystic ovary syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis, and peripheral levels of androgens. In previous studies, we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as granulosa cell functions. We propose that theca cells impact follicle integrity by regulating androgen production and action, as well as granulosa cell differentiation/luteinization in response to androgens and gonadotropins that may underlie PCOS.