Antimony (Sb) is an estrogenic metal. Exogenous exposure to Sb can affect estrogen levels and their receptor expression in organisms, exerting estrogen-disrupting effects and even inducing polycystic ovary syndrome (PCOS), which is accompanied by the progression of ovarian fibrosis. To investigate the pathological mechanism of this reproductive damage caused by Sb exposure, we exposed female zebrafish to Sb solution for 18 days for acute toxicity experiments. The results showed that Sb exposure affected the changes of GnRH, FSH, LH, E2 and T levels on the HPG axis, which disrupted the balance of sex steroid hormones in the internal environment of zebrafish and progression of PCOS. Furthermore, Sirius red staining revealed significant fibrosis in the ovarian tissues of Sb-exposed female zebrafish. This study adopted transcriptome sequencing and Western Blotting to explore the mechanisms of action. The biological processes and signaling pathways potentially associated with Sb-induced ovarian fibrosis were predicted by using GO annotation and KEGG pathway enrichment analysis, such as ECM receptors, TGF-β/Smad and WNT/β-catenin. The experiment results showed that Sb induced up-regulation of the transcription levels of the pro-fibrotic factors tgf-β3, wnt10a, ctnnb1, and β-catenin protein expression, suggesting the activation of the WNT/β-catenin pathways and TGF-β/Smad. Sb exposure led to up-regulation of ECM-related genes col2a1a, itgb1b.2, lamc1, fn1a and up-regulation of fibrosis markers α-SMA, Fn1a, col4a2 protein expression, Therefore, we hypothesized that Sb exposure activates the TGF-β/Smad and WNT/β-catenin pathways, leading to abnormal ECM deposition and promoting the progression of ovarian fibrosis in zebrafish.

Dysregulated amino acid metabolism is a key contributor to polycystic ovary syndrome (PCOS). This cross-sectional study revealed that serum levels of L-kynurenine (L-Kyn) were significantly elevated in women with PCOS, whereas pyridoxal 5'-phosphate (PLP) levels were markedly reduced. Moreover, human serum L-Kyn levels exhibited a positive correlated with low-density lipoprotein cholesterol (LDL-C) and a negative correlation with high-density lipoprotein cholesterol (HDL-C). Additionally, letrozole (LET) induced PCOS-like mice displayed increased hepatic L-Kyn levels. Mechanistically, both in vivo and in vitro experiments demonstrated that the upregulation of indoleamine 2,3-dioxygenase (IDO1) activates the aryl hydrocarbon receptor (AHR) - proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway in the liver of PCOS-like mice, thereby contributing to dyslipidemia. Treatment with epacadostat, an inhibitor of the enzyme IDO1, or PLP, a cofactor for L-Kyn catabolism, effectively restored ovarian function, improved glucose tolerance, and ameliorated lipid profile abnormalities in PCOS-like mice.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder often associated with obesity and insulin resistance (IR), though the role of thioredoxin-interacting protein (TXNIP) in obesity-induced IR in PCOS remains unclear. This study explores the relationship between TXNIP levels and obesity-associated IR in women with PCOS.

A case-control study was conducted from January 2019 to December 2020, including 161 women with PCOS and 107 healthy controls. PCOS patients were categorized into insulin-resistant (IR) and non-IR subgroups, further divided by BMI into obese, overweight, and normal weight groups. The metabolic parameters such as cholesterol, triglycerides, fasting blood glucose, homocysteine, and serum TXNIP levels were measured. Logistic regression assessed the relationship between TXNIP expression and metabolic dysfunction.

TXNIP levels were significantly higher in the PCOS group compared to controls (67% increase), with a further 56% increase in the IR subgroup. The TXNIP levels were elevated in the obese group compared to overweight and normal weight groups (P < 0.05). TXNIP expression was negatively correlated with obesity (R = - 0.116, P = 0.007) and HDL cholesterol (R = - 0.196, P = 0.001), but positively associated with triglycerides (R = 0.181, P = 0.003) and homocysteine (R = 0.130, P = 0.034). After adjusting for confounders, TXNIP remained significantly associated with IR (P < 0.05). TXNIP demonstrated excellent diagnostic performance in distinguishing IR from non-IR PCOS patients, with an AUC of 0.89 (95% CI 0.84-0.94; P < 0.001).

TXNIP is significantly correlated with IR in women with PCOS, highlighting its potential as a biomarker for metabolic abnormalities. Further research is needed to fully understand its role in obesity-induced IR in PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. Hyperandrogenemia (HA) is a hallmark of PCOS and is positively associated with metabolic complications. Androgens exert their biological actions through the androgen receptor (AR), which regulates transcriptional activity. Antiandrogens are not recommended for managing metabolic complications in PCOS due to their hepatotoxicity, despite being a viable therapy to treat HA. We hypothesized that the novel AR Proteolysis Targeting Chimera (PROTAC) degrader ARV-110 would downregulate AR protein levels and actions to abolish or mitigate HA-mediated metabolic complications using a well-established HA mouse model of PCOS. Three-week-old female mice were implanted with dihydrotestosterone (DHT) or control pellets. Four weeks later, mice were treated with low- (ARV-110-L, 1 mg/kg.day) or high-dose (ARV-110-H, 10 mg/kg.day) ARV-110 for an additional 8 weeks. ARV-110 dose-dependently reduced AR protein levels in white adipose tissue (WAT), kidney, liver, and ovary. ARV-110 attenuated DHT-induced increases in body weight, fat mass, kidney mass, WAT mass, circulating leptin and antimüllerian hormone, and altered glucose homeostasis. ARV-110-H increased kidney (UACR, KIM-1, NGAL) and liver (ALT, AST, LDH) injury markers and caused severe hepatomegaly, while ARV-110-L mostly spared those deleterious effects. Unbiased proteomics analysis revealed that ARV-110-H treatment severely affected the liver proteome and dysregulated multiple signaling and metabolic canonical pathways, while only minimal effects were observed with ARV-110-L treatment. In summary, our findings underscore the potential of AR PROTACs as a novel therapeutic approach for managing metabolic complications in PCOS, provided the dosing is carefully optimized to avoid adverse effects.

The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.

Polycystic ovary syndrome (PCOS) is strongly associated with metabolic abnormalities, with 50-70% of patients exhibiting insulin resistance (IR), which significantly impacts the reproductive health of women in their reproductive years. Growth differentiation factor 15 (GDF15), a hormone responsive to nutritional stress, has been implicated in several diseases. This study sought to clarify the relationship between GDF15 levels and IR condition in PCOS patients. Based on the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), patients were categorized into an IR-PCOS group (n = 124) and a non-insulin-resistant group (non-IR-PCOS group, n = 109). Fasting blood samples were collected to measure GDF15 concentrations. To assess metabolic complications in relation to GDF15 levels, patients were also classified into high and normal GDF15 groups. Serum GDF15 levels were significantly higher in IR-PCOS patients (median 772.94 pg/ml) compared to non-IR-PCOS patients (median 575.80 pg/ml, P < 0.05). The high GDF15 group showed more severe metabolic and lipid abnormalities than the normal GDF15 group. Spearman correlation analysis revealed a correlation between increased GDF15 levels and impaired glucose metabolism. Logistic regression analysis identified GDF15, HDL-C, and prolactin as risk factors for IR in PCOS, and the fully adjusted regression coefficient for GDF15 levels and IR prevalence was 4.490 (95% CI 1.541 to 13.088). Restricted cubic spline analysis confirmed a positive association between GDF15 levels and IR within a specific range. The combined predictive probability of GDF15, prolactin, and HDL-C for IR was 0.763 (95% CI 0.701 to 0.826) according to ROC analysis. Elevated GDF15 levels may be associated with IR in PCOS patients, suggesting a potential role for GDF15 in the pathophysiology of IR in this condition.

Polycystic ovary syndrome (PCOS) occurs in women of reproductive age, impairing reproductive and metabolic processes. Variations in the cathepsin B (CTSB) gene can influence the disease prognosis by changing the activity, stability, or expression. These single-nucleotide polymorphisms (SNPs) can affect critical cellular functions like the deposition of extracellular matrix, inflammation, and tissue repair, leading to the development of multifactorial diseases. Our study aims to investigate the association between PCOS risk and CTSB SNPs. In this case-control study, 150 PCOS cases and 150 healthy women were enrolled. Genotyping was conducted using the PCR-RFLP method. Different computational databases were used to predict the impact of variations on the splicing sites. Regarding rs12898, the codominant homozygous (GG vs. AA) and recessive (GG vs. AA + AG) inheritance models reduced PCOS risk by 72% and 71%, respectively. PCOS risk was increased by 2.81, 2.94, 1.62, and 2.20 folds in the codominant (TT vs. CC), recessive (TT vs. CC + CT), T vs. C (rs8898), and T vs. C (rs3779659) modes, respectively. Based on haplotype analysis, Ars12898Trs8898Crs3779659, and Ars12898Crs8898Trs3779659 haplotypes significantly enhance PCOS risk by 1.57 and 3.34 folds, respectively. Furthermore, the interaction analysis indicated that AGrs12898/TTrs8898/CCrs3779659 and AAs12898/TTrs8898/CCrs3779659 genotype combinations strongly correlated with high PCOS risks by 2.59 and 4.20 folds, respectively. The CTSB rs12898 G > A and rs8898 C > T can potentially create or disrupt binding sites for several splicing factors. CTSB rs12898, rs8898, and rs3779659 SNPs were associated with PCOS risk in our population. Larger sample sizes will be necessary to confirm these findings and investigate other potential causal factors involved in PCOS etiology.

The pathophysiology of polycystic ovary syndrome (PCOS) is complex and heterogeneous. This systematic review and meta-analysis aimed to determine the triglyceride-glucose index and lipid ratios in women with and without PCOS.

Literature searches were performed in PubMed, Scopus, Web of Science, Scielo, and Embase for studies reporting the triglyceride-glucose index and total cholesterol/high-density lipoprotein (HDL)-cholesterol, triglyceride/HDL-cholesterol, and low-density lipoprotein (LDL)-cholesterol/HDL-cholesterol ratios. Results are reported as standardized mean differences (SMDs) along with their 95% confidence intervals (CIs).

The search identified 61 observational studies, including case-control (n = 37), cohort (n = 2), and cross-sectional (n = 22) studies reporting results of interest according to different PCOS diagnosis criteria. Compared with the control group, the PCOS group presented increased circulating triglyceride-glucose index (n = 9 studies, SMD, 0.41; 95% CI, 0.08-0.74) and total cholesterol/HDL-cholesterol (n = 35 studies, SMD, 1.70; 95% CI, 0.69-2.70), triglyceride/HDL-cholesterol (n = 31 studies; SMD, 0.81; 95% CI, 0.43-1.19), and LDL-cholesterol/HDL-cholesterol (n = 25 studies, SMD, 2.40; 95% CI, 0.45-4.35) ratios. Statistical heterogeneity values were very high (I 2 > 90%). The PCOS group displayed significantly higher body mass index and homeostatic model assessment of insulin resistance. The PCOS group was younger than the control group and had a higher total cholesterol/HDL-cholesterol ratio, and other lipid variables were comparable in all groups.

Patients with PCOS show significantly higher triglyceride-glucose index and total cholesterol/HDL-cholesterol, triglyceride/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol ratios than those without the syndrome.

This retrospective study aimed to examine the influence of hormonal and metabolic parameters across varying body mass index (BMI) levels on embryo quality and pregnancy outcomes in fresh embryo transfer cycles using assisted reproductive technology (ART) in patients diagnosed with polycystic ovary syndrome (PCOS).

A total of 167 women diagnosed with PCOS and 266 women without PCOS (control group) were included. Metabolic and hormonal parameters was compared between the two groups to evaluate their relationship with embryo quality and pregnancy outcomes. Subgroup analyses were performed to assess these effects in patients with normal and high BMI.

In the PCOS group, hormonal and metabolic parameters such as insulin, blood lipids, luteinizing hormone (LH), anti-Müllerian hormone (AMH) and antral follicle counting (AFC) were significantly higher than in the control group. The PCOS group also produced more blastocysts and a higher proportion of high-quality blastocysts. However, pregnancy rate and clinical pregnancy rates were similar between the two groups, regardless of BMI. Among the high-BMI PCOS patients, the miscarriage rate was significantly higher compared to the control group, and its rate showed a positive correlation with BMI, LH, and total testosterone (TSTO) levels.

Hormonal imbalances and glucose-lipid metabolism have minimal influence on embryo development in PCOS patients. However, hormonal factors-particularly in PCOS patients with high BMI-significantly influence pregnancy outcomes, with elevated BMI and androgen levels increasing the risk of miscarriage. These findings underscore the importance of addressing metabolic and hormonal factors in the management of PCOS patients undergoing ART.

Although recent studies indicate a high prevalence of subclinical hypothyroidism (SCH) in women with polycystic ovary syndrome (PCOS), the reported prevalence rates vary widely. Therefore, we conducted this study to estimate the pooled prevalence of SCH among women with PCOS. Additionally, emerging evidence suggests that SCH may negatively impact insulin resistance in PCOS. Thus, we examined its effect on insulin resistance indices as our secondary objective.

We searched PubMed, Web of Science, Scopus, and Embase from their inception to February 25, 2024. Observational studies reporting the prevalence of SCH among women with PCOS were included. Joanna Briggs Institute's (JBI) critical appraisal checklist for prevalence studies was adopted for the risk of bias assessment. The random-effects model was employed to estimate the pooled prevalence with its 95% confidence intervals (CI). The weighted mean difference (WMD) was used to compare the insulin resistance indices between PCOS patients with and without SCH.

Twenty-nine studies comprising 5765 women with PCOS were included. The meta-analysis demonstrated that 19.7% (95% CI: 16.1%; 23.5%) of women with PCOS have SCH. PCOS patients with SCH had significantly higher HOMA-IR (WMD = 0.78, 95% CI: 0.34; 1.22) and fasting insulin (WMD = 2.38, 95% CI: 0.34; 4.42) levels than those without SCH. Differences in fasting plasma glucose and 2-hour postprandial glucose did not reach statistical significance.

This systematic review and meta-analysis found that approximately 20% of women with PCOS have SCH. This underscores the need for regular thyroid function testing in these patients. The prevalence of SCH is influenced by the TSH cut-off used for diagnosis, highlighting the need for establishing a standardized TSH cut-off value. Furthermore, SCH significantly elevates the HOMA-IR index and fasting insulin levels, highlighting its potential impact on insulin resistance. Whether these metabolic changes are clinically important and put these individuals at higher risk of developing type 2 diabetes mellitus and cardiovascular disease requires further investigation.

CRD42024510798.

Not applicable.

Serum AMH levels in adult women are part of the diagnostic criteria for polycystic ovary syndrome (PCOS), a condition with marked infertility and metabolic risks. Yet, little is known about AMH levels among women from ethnic minority populations, especially its associations with age and obesity. The objective is to describe the association of age and serum anti-mullerian hormone (AMH) among Samoan women, provide age specific AMH reference levels, and examine the associations of AMH with adiposity and reproductive factors.

A cross-sectional, retrospective study of a representative community-based sample from Samoa was conducted. 670 women with no known reproductive disorders, reproductive surgeries, or hormonal contraceptive use, age 25-51 years, were included. Adiposity was assessed by body mass index (BMI) using Polynesian-specific criteria for obesity. Serum AMH was determined by enzyme-linked immunosorbent assay. Serum total testosterone and sex hormone binding globulin were measured, and the free androgen index was calculated. Hormonal contraceptive use, menstrual regularity, and tobacco use were assessed by questionnaire. PCOS prevalence was estimated using current guidelines.

Despite a high prevalence of obesity and overweight in Samoan women, serum AMH and its age related decline were similar to those reported in other populations. AMH was negatively associated with age. AMH decline with age in Samoan women is best described by a cubic model. AMH was not associated with BMI or insulin resistance. PCOS prevalence was estimated at 3.4-5.1%.

This study was the first to construct an age specific AMH reference range for Samoan women. PCOS prevalence appears low, supporting other published studies that have demonstrated a complex relationship between adiposity and reproductive health in Samoan women.

Not applicable.

Polycystic ovary syndrome (PCOS) is linked to non-alcoholic fatty liver disease (NAFLD). Biochemical, sex hormonal, and anthropometric indicators have been explored for screening NAFLD in PCOS patients. However, the accuracy of NAFLD screening using these indicators in PCOS patients remains uncertain. This study aimed to identify biochemical, sex hormonal, and anthropometric indicators associated with NAFLD in overweight and obese PCOS patients and assess the diagnostic efficacy of combined indicators.

This cross-sectional study (Clinical trial number ChiCTR1900020986; Registration date January 24th, 2019) involved 87 overweight or obese women with PCOS (mean age 29 ± 4 years). Measurements included anthropometric indices, biochemistry, sex hormone levels, and liver proton density fat fraction (PDFF). Correlation analysis, intergroup comparisons, and logistic regression analysis were used to identify risk factors for NAFLD (PDFF > 5.1%). The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value were used to determine cut-off values and evaluate diagnostic accuracy.

Liver PDFF was 7.69% (3.93%, 14.80%) in overweight and obese PCOS patients, with 67.8% diagnosed with NAFLD. NAFLD was associated with increased body mass index (BMI), abdominal circumference (AC), and triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), glucose, insulin, and free testosterone (FT) levels, and with decreased high-density lipoprotein-cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels (P < 0.05). Risk factors for NAFLD in PCOS included BMI > 26.8 kg/m2, AC > 88.3 cm, triglyceride > 1.57 mmol/L, TC > 4.67 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, FT > 7.6 pg/mL and SHBG < 25 nmol/L (β = 1.411-2.667, P < 0.005). A multi-indicator model including triglycerides, LDL-C, glucose, insulin, and SHBG showed higher diagnostic accuracy (AUC = 0.899, P < 0.001) for screening NAFLD in PCOS patients than single indicators (AUC = 0.667-0.761, P < 0.05).

Overweight and obese PCOS patients have higher incidences of liver PDFF and NAFLD. A multi-indicator model including triglycerides > 1.57 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, and SHBG < 25 nmol/L is highly accurate for screening NAFLD in overweight and obese PCOS patients.

Polycystic Ovarian Syndrome is a leading gynecological condition that is being known to affect women fertility irrespective of their reproductive age. Though its prevalency and adverse effects in causing the female infertility is know to be reported worldwide, it has the steroidal pills having remarkable side effects as their effective medication to treat and manage its symptoms. Inorder to find a novel curative plant besed therapy, this study investigates the therapeutic potential of Terminalia chebula Retz. to manage the complications of PCOS. In this present study, the bioactive compounds of Terminalia chebula Retz. fruit extract were identified by GC-MS and the experimental animals (female Wistar rats) were categorized into six groups including control, letrozole-induced PCOS group, metformine treated as standard control, along with the groups orally treated with T. chebula fruit extracts at various concentrations. As a result of PCOS induction, the level of LPx got increased evidencing the increased lipid metabolism where the other antioxidant levels were decreased. The serum hormonal profile revealed a considerable decrease in estrogen and progesterone levels while the levels of LH, FSH, testosterone, and insulin were increased. The mRNA and protein expressions of CYP17A1, was upregulated whereas the CYP19A1 and PPAR-γ found to have lower expression on concerning the control group. These entire physiological, and biochemical observed during the successful induction of PCOS got restored to normal after being treated with the fruit extract of T. chebula in the experimental animals and implied its potentiality in managing the complications of PCOS.

To identify potential biomarkers in patients with polycystic ovary syndrome (PCOS) and atherosclerosis, and to explore the common pathologic mechanisms between these two diseases in response to the increased risk of cardiovascular diseases in patients with PCOS.

PCOS and atherosclerosis data sets were downloaded from the GEO database, and their differentially expressed genes were identified. Weighted gene co-expression network analysis was used to obtain intersection genes, and then protein-protein interaction and functional enrichment analysis were performed. Machine learning algorithms were used to select the key genes, which were then validated through external data sets. We constructed a nomogram to predict the risk of atherosclerosis in women with PCOS. Finally, the CIBERSORT algorithm was used to analyze the infiltration of immune cells in the atherosclerosis group.

We identified six hub genes (CD163, LAPTM5, TNFSF13B, MS4A4A, FGR, and IRF1) that exhibited excellent diagnostic value in validation data sets. Gene ontology terms and KEGG signaling pathway analysis revealed that key genes were associated with immune responses and inflammatory reactions. Abnormal immune cell infiltration was also found in the atherosclerosis group and was correlated with the six hub genes.

Common therapeutic targets of PCOS and atherosclerosis were preliminarily identified through bioinformatics analysis and machine learning techniques. These findings provide new treatment ideas for reducing the risk that PCOS will develop into atherosclerosis.

Polycystic ovary syndrome (PCOS) and autoimmune thyroid disease (AITD) have a high prevalence in women of reproductive age. PCOS can lead to long-term adverse health effects such as obesity, diabetes, and increased metabolic and cardiovascular risk. Although it is known that subclinical and clinical hypothyroidism may also worsen body mass index (BMI), lipid profile, and metabolic risk, there are few studies on the impact of elevated thyroid autoantibodies alone and associated chronic inflammation on metabolic complications in women with PCOS. The main aim of the study was to assess the prevalence of AITD among Polish women with PCOS and the metabolic impact of the co-occurrence of both diseases in euthyroid individuals. The additional aim was a review of the literature on the prevalence of co-occurrence of PCOS and AITD and the metabolic consequences of this condition.

A total of 424 women aged 16-46 years were recruited into the study-230 women diagnosed with PCOS and 194 women diagnosed with PCOS and co-occurrence of euthyroid AITD. Before participating in the study, patients signed a written informed consent. The study was approved by the local ethics committee. Statistical analysis was performed using IBM SPSS Statistics (v.25). A mini-review of the literature was performed using the PubMed database.

Women with co-occurrence of PCOS and euthyroid AITD had statistically significantly higher serum levels of total cholesterol (189.57 mg/dL vs. 180.16 mg/dL; p = 0.005; d Cohen's = -0.278), LDL-cholesterol (109.80 mg/dL vs. 102.01 mg/dL; p = 0.009; d Cohen's = -0.256), and triglycerides (107.77 mg/dL vs. 96.82 mg/dL; p = 0.027; d Cohen's = -0.219) compared to women with PCOS. The difference was observed regardless of body weight. BMI was also statistically significantly higher in the PCOS-AITD group (27.55 kg/m2 vs. 25.46 kg/m2; p = 0.003; d Cohen's = -0.319), as was the prevalence of obesity (32.5% vs. 20.7%; Chi-square = 7.956; p = 0.047). The mini-review of the literature did not find many studies evaluating the impact of thyroid autoantibodies on metabolic outcomes in PCOS euthyroid women, and the data are still inconclusive.

The presence of elevated serum concentrations of thyroid autoantibodies in euthyroid women with PCOS increases the risk of obesity and metabolic consequences. It is observed even in euthyroid and non-obese individuals. Consequently, the cardiovascular risk in these women may be higher than in PCOS women without elevated thyroid autoantibodies. It is important to assess thyroid autoantibodies in all women with PCOS. In euthyroid PCOS women with co-occurrence of elevated serum levels of thyroid autoantibodies, it is crucial to pay more attention to maintaining an appropriate body mass index. There is an urgent need for further studies in large groups of women assessing the impact of elevated thyroid autoantibodies alone on metabolic outcomes in euthyroid women with PCOS to confirm and clarify the results.

To determine whether long-term administration of synbiotics affects clinical, endocrine and metabolic aspects of polycystic ovary syndrome (PCOS) in overweight and obese subjects undergoing intensive lifestyle modifications.

During six-month trial, all subjects underwent intensive lifestyle modifications (diet and exercise). The subjects were randomized (1:1) to receive synbiotic supplementation (Synbiotic Group) or placebo (Placebo Group).

Subjects in the Placebo Group and the Synbiotic Group experienced significant reduction of BMI (- 8% and - 11%, respectively; both at P < 0.0001) and body fat percentage (- 11% and - 14%, respectively; both at P < 0.0001). These effects were statistically comparable for both groups. Total testosterone was not significantly changed in the Placebo Group (- 5%, P = 0.41) while it greatly declined in the Synbiotic Group (- 40%; P < 0.0001); the difference between these groups was significant (P = 0.0002). Synbiotic supplementation was superior to placebo in reducing LH (- 21%; P = 0.047), total cholesterol (- 6%; P = 0.002), low-density lipoprotein cholesterol (- 6%; P = 0.044), triglycerides (- 29%; P = 0.049), LPS (- 23%; P = 0.001) and LPS-binding protein (- 21%; P = 0.001).

Synbiotic supplementation led to a marked improvement of several key clinical and laboratory aspects of PCOS including an improvement of hyperandrogenism, lipid profile, and markers of endotoxemia.

Clinical Trial Registration Number: NCT03325023 (URL, clinicaltrials.gov; date of registration 10/26/2017).

This study aimed to identify shared gene expression related to circadian rhythm disruption in polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) to discover common diagnostic biomarkers. Visceral fat RNA samples were collected from 12 PCOS and 14 non-PCOS patients, a sample size representing the clinical situation and sufficient to capture PCOS gene expression profiles. Along with liver transcriptome profiles from NAFLD patients, these data were analyzed to identify crosstalk circadian rhythm-related genes (CRRGs) between the diseases. Single-sample and single-gene gene set enrichment analyses explored immune infiltration and pathways associated with CRRGs. Diagnostic biomarkers were identified using a random forest algorithm and validated through nomograms and a mouse model. Seven crosstalk CRRGs (FOS, ACHE, FOSB, EGR1, NR4A1, DUSP1, and EGR3) were associated with clinical features, immunoinflammatory microenvironment, and metabolic pathways in both diseases. EGR1, DUSP1, and NR4A1 were identified as diagnostic biomarkers, exhibiting robust diagnostic capacity (AUC = 0.7679 for PCOS, AUG = 0.9981 for NAFLD). Nomogram validation showed excellent calibration, and independent datasets confirmed their discriminatory ability (AUC = 0.6528 for PCOS, AUC = 0.8275 for NAFLD). Additionally, ceRNA networks and androgen receptor binding sites were identified, suggesting their regulatory roles. Mouse model validation confirmed significant downregulation of EGR1, DUSP1, and NR4A1 in liver tissues, consistent with sequencing data. This study identifies crosstalk CRRGs and diagnostic biomarkers shared between PCOS and NAFLD, highlighting their roles in immune and metabolic dysregulation. These biomarkers offer the potential for improving diagnosis and guiding targeted treatments for both diseases.

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder found in women of reproductive age and is characterized by both metabolic and reproductive dysfunction. Women with PCOS commonly have insulin resistance, increased susceptibility to type 2 diabetes mellitus, dyslipidemia, hyperinsulinemia, increased cardiovascular risk, hepatic steatosis, infertility, and an overall reduction in physical and psychological well-being. Several previous studies have shown a causal association between PCOS and hepatic disorders, such as chronic liver disease (CLD) and nonalcoholic fatty liver disease (NAFLD), where PCOS was identified as contributing to the hepatic features. Whilst it is recognized that PCOS may contribute to hepatic dysfunction, there is also evidence that the liver may contribute to the features of PCOS. The purpose of this review is to discuss the current understanding regarding hepatic involvement in PCOS pathophysiology, the inflammatory markers and hepatokines involved in the development of PCOS, and the role of genetics in the occurrence of PCOS. This review illustrates that PCOS and NAFLD are both common disorders and that there is both genetic and metabolic linkage between the disorders. As such, whilst PCOS may contribute to NAFLD development, the converse may also be the case, with a potential bidirectional relationship between PCOS and liver disease.

It is well known that both women with polycystic ovary syndrome (PCOS) and women with gestational diabetes mellitus (GDM) have increased risks of adverse pregnancy outcomes, but little is known whether the combination of these two conditions exacerbates the risks. We explored risk estimates for adverse pregnancy outcomes in women with either PCOS or GDM and the combination of both PCOS and GDM.

Nationwide register-based historical cohort study in Sweden including women who gave birth to singleton infants during 1997-2015 (N = 281 806). The risks of adverse pregnancy outcomes were estimated for women exposed for PCOS-only (n = 40 272), GDM-only (n = 2236), both PCOS and GDM (n = 1036) using multivariable logistic regression analyses. Risks were expressed as odds ratios with 95% confidence intervals (CIs) and adjusted for maternal characteristics, including maternal BMI. Women with neither PCOS nor GDM served as control group. Maternal outcomes were gestational hypertension, preeclampsia, postpartum hemorrhage, and obstetric anal sphincter injury. Neonatal outcomes were preterm birth, stillbirth, shoulder dystocia, born small or large for gestational age, macrosomia, low Apgar score, infant birth trauma, cerebral impact of the infant, neonatal hypoglycemia, meconium aspiration syndrome and respiratory distress.

Based on non-significant PCOS by GDM interaction analyses, we found no evidence that having PCOS adds any extra risk beyond that of having GDM for maternal and neonatal outcomes. For example, the adjusted odds ratio for preeclampsia in women with PCOS-only were 1.18 (95% CI 1.11-1.26), for GDM-only 1.77 (95% CI 1.45-2.15), and for women with PCOS and GDM 1.86 (95% CI 1.46-2.36). Corresponding adjusted odds ratio for preterm birth in women with PCOS-only were 1.34 (95% CI 1.28-1.41), GDM-only 1.64 (95% CI 1.39-1.93), and for women with PCOS and GDM 2.08 (95% CI 1.67-2.58). Women with PCOS had an increased risk of stillbirth compared with the control group (aOR 1.52, 95% CI 1.29-1.80), whereas no increased risk was noted in women with GDM (aOR 0.58, 95% CI 0.24-1.39).

The combination of PCOS and GDM adds no extra risk beyond that of having GDM alone, for a number of maternal and neonatal outcomes. Nevertheless, PCOS is still an unrecognized risk factor in pregnancy, exemplified by the increased risk of stillbirth.

Metabolic disorders in polycystic ovary syndrome (PCOS) patients have attracted increasing attention, and nonalcoholic fatty liver disease (NAFLD) in particular has been the focus of much research due to its high incidence and potential harm in patients with PCOS. However, little is known about whether PCOS is associated with more severe NAFLD histopathology. Although Jiawei Qi Gong Wan (JQGW) is widely used clinically, its specific effects and mechanisms on the liver remain unclear.

The aim of this study was to explore the mechanism of JQGW in improving metabolic abnormalities in the liver in PCOS mice in order to support the development of therapies to prevent PCOS complications.

A mouse model of PCOS was established by subcutaneously implanting letrozole tubes. The effect of JQGW on liver metabolism in mice was observed by measuring biochemical indicators in serum. Liver morphological changes were observed using hematoxylin and eosin staining along with Sirius red staining, while Western blotting and qRT-PCR were used to quantify the expression of genes and proteins related to liver fibrosis and inflammation processes. Network pharmacology was used to analyze the key factors that JQGW may target in improving liver fibrosis in PCOS mice, and the results were verified by Western blotting of liver tissue from PCOS mice.

PCOS mice had obvious liver metabolic dysfunction, inflammation, and fibrosis, all of which could be reversed by JQGW. Network pharmacology functional enrichment revealed that the overlapping targeted genes were enriched mainly in insulin resistance-related pathways and androgen-related pathways. We verified related proteins and found that JQGW improved liver fibrosis and inflammation in PCOS mice mainly by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways.

JQGW can improve liver metabolic function in a letrozole-induced PCOS mouse model by inhibiting liver fibrosis and inflammation, and it acts mechanistically by regulating the Akt2-FoxO1 and YAP/TAZ signaling pathways. Our findings thus provide a valuable reference for the advancement of therapeutic strategies aimed at addressing PCOS patients with abnormal liver metabolism.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age and is characterized by menstrual irregularities, metabolic imbalances and infertility. The pathogenesis of PCOS is complex and not fully understood, and chronic inflammation and insulin resistance are implicated in its progression. In this study, we investigated the role of m6A methylation, an important epigenetic modification, in the pathogenesis of PCOS. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq), we mapped the m6A methylation profile in granulosa cells from patients with PCOS and identified a significant regulatory effect on gene expression. CD36 is a novel m6A-regulated gene that may facilitate the progression of PCOS. We demonstrated that METTL3, an m6A methyltransferase, modulated CD36 expression and influenced glucose metabolism and inflammatory responses in PCOS. Employing KGN cells as a model of insulin resistance, we observed that CD36 knockdown ameliorated the impaired glucose uptake and significantly reduced the production of pro-inflammatory cytokines. These findings are consistent with the results of CD36 inhibition in a mouse model of PCOS, indicating a role of CD36 in modulating the disease phenotype. Our study delineates a previously unrecognized epigenetic mechanism involving m6A methylation in PCOS, highlighting the potential of targeting the METTL3-CD36 axis as a therapeutic strategy for managing ovarian inflammation and metabolic dysregulation in patients with PCOS.

Polycystic ovary syndrome (PCOS) involves complex genetic, metabolic, endocrine, and environmental factors. This study explores the effects of nicotinamide mononucleotide (NMN) in a letrozole-induced PCOS mouse model, focusing on metabolic regulation. Letrozole-induced aromatase inhibition elevated androgen and reduced bile acid levels, linking liver dysfunction and gut imbalance to PCOS. Letrozole-treated mice exhibited disrupted estrous cycles, ovarian congestion, and elevated testosterone. NMN intervention alleviated hyperandrogenism, ovarian abnormalities, and bile acid decline but did not fully restore the estrous cycle or improve lipid profiles. Metabolomic analysis showed that NMN partially reversed bile acid and lipid metabolism disturbances. These findings highlight NMN's protective role in reducing hyperandrogenism and ovarian cyst formation. However, effective PCOS treatment should target liver and gut metabolism, not just ovarian symptoms, to mitigate systemic effects. Bile acid dysregulation may play a key role in PCOS progression and warrants further investigation.

Polycystic Ovarian Syndrome (PCOS) is a prevalent metabolic and hormonal disorder affecting women of reproductive age. Limited data exists on Syrian women's PCOS awareness and health behaviors. This study aimed to gauge PCOS prevalence, knowledge, awareness, and health-related practices among Syrian women. A cross-sectional online survey was conducted from 11 February to 27 October 2022, targeting Syrian women aged 18-45. Collaborators from specific medical universities distributed a questionnaire adapted from a Malaysian paper through social media platforms. Out of 1840 surveyed Syrian women, 64.2% were aged 21-29, and 69.6% held bachelor's degrees. Those with a bachelor's degree exhibited the highest mean knowledge score (12.86), and women previously diagnosed with PCOS had a higher mean knowledge score (13.74) than those without. Approximately 27.4% were confirmed PCOS cases, and 38.9% had possible cases. Women with PCOS were 3.41 times more likely to possess knowledge about the condition. The findings suggest a moderate level of PCOS knowledge and health-related practices among Syrian women, emphasizing the need for increased awareness. Consistent local PCOS screening programs, in collaboration with obstetrics and gynecology professionals, are crucial for improving understanding and clinical symptom recognition of this condition among Syrian women.

This study aimed to investigate the impact of serum androgen levels on metabolic profiles in patients with polycystic ovary syndrome (PCOS).

We included 216 patients with PCOS and 216 healthy individuals selected as the control group. According to the measured serum androgen levels, patients with PCOS were divided into the hyperandrogenism group and non-hyperandrogenism group. Clinical metabolic indicators were assessed and compared between the two groups. Additionally, we assessed the correlation between androgen levels and clinical metabolic indicators.

The body mass index, waist-to-hip ratio, mF-G score, and acne score, as well as T, LH, LSH/FSH, FPG, Cr, UA, TG, TC, and LDL-C levels were significantly higher in the PCOS group than in the control group. The incidence of hyperandrogenism and clinical hyperandrogenism in the PCOS group was significantly higher than that in the control group. Regarding clinical hyperandrogenism, hirsutism, acne, and acanthosis nigricans were significantly more common in the PCOS group than in the control group. Serum androgen levels were significantly correlated with the mF-G score, acne score, FSH, glucose concentration at 30 min, glucose concentration at 60 min, glucose concentration at 120 min, FINS, N120, HOMA-IR, HbA1c, AUCG, UA, TG, and hHDL-Clevels.

Elevated serum androgen levels are commonly observed in patients with PCOS and are associated with multiple metabolic abnormalities. Therefore, it is recommended to regularly monitor glucose and lipid metabolism-related indicators in patients with PCOS who have elevated androgen levels.

Polycystic ovary syndrome (PCOS) is a common, heterogeneous clinical syndrome affecting women. Investigating oxidative stress in women is crucial, as it is linked to insulin resistance and endothelial dysfunction. Chlorogenic acid, a bioactive component found in green coffee, has numerous documented health benefits. This study aimed to assess the beneficial effects of green coffee consumption on paraoxonase-1 (PON-1) activity and malondialdehyde (MDA) levels in women with PCOS.

This study was a double-blind randomized clinical trial that included 44 patients with PCOS. Participants were randomly assigned to either the intervention or control group. For 6 weeks, the intervention group (n=22) received 400 mg of green coffee supplements, while the control group (n=22) received 400 mg of a starch-based placebo. Anthropometric indices, dietary assessments, and physical activity levels were evaluated before and after the 6-week intervention period. Additionally, blood samples were collected for laboratory analysis.

Supplementation with green coffee increased PON-1 levels by 3.5 units, a significant finding (p=0.038). Additionally, the intake of green coffee supplements significantly reduced blood cholesterol levels by 18.8 units (p=0.013) and triglyceride levels by 6.1 units (p=0.053). However, no significant differences were observed in the levels of MDA, high-density lipoprotein, low-density lipoprotein, fasting blood sugar, insulin, or homeostatic model assessment of insulin resistance as a result of the intervention.

Supplementation with green coffee alters PON-1 activity and cholesterol levels in women with PCOS. However, it has no significant impact on MDA levels or glycemic status.

Objectives: This study aimed to explore the effect and mechanism of Yunkang oral liquid (YK) on polycystic ovary syndrome (PCOS). Methods: PCOS model rats were prepared by injecting exogenous androgen dehydroepiandrosterone, and YK was administered simultaneously for 28 days during modeling. The morphology of ovaries and uterus was observed using H&E staining, and serum levels of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. Additionally, serum lipids (TG, HDL-c), blood glucose (GLU), and aminotransferase (AST, ALT) levels were detected. The expression of androgen receptor (AR) protein was determined by Western blotting. Results: YK treatment resulted in reduced serum levels of T, LH and FSH, ameliorated ovarian polycystic-like pathological changes and uterine morphology in PCOS rats, and decreased serum TG, GLU, AST and ALT levels, elevated serum HDL-c levels, and improved abnormalities of glycolipid metabolism accompanying PCOS. Moreover, YK decreased the expression of ovarian AR in PCOS rats. Conclusions: This study indicates that YK may protect the ovaries by inhibiting the expression of AR, which could be a potential treatment for PCOS.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often accompanied by various symptoms including significant pain, such as dysmenorrhea, abdominal, and pelvic pain, which remains underexplored. This retrospective study examines electronic health records (EHR) data to assess the prevalence of pain in women with PCOS. Conducted on May 29, 2024, using data from 120 Health Care Organizations within the TriNetX Global Network, the study involved 76,859,666 women from diverse racial backgrounds. The analysis focused on the prevalence of pain among women with PCOS, both overall and in those prescribed PCOS-related medications. Relative risk ratios (RR) were calculated for future health outcomes and stratified by self-reported race. The study found that 19.21% of women with PCOS experienced pain, with the highest prevalence among Black or African American (32.11%) and White (30.75%) populations. Both the PCOS and PCOS and Pain cohorts exhibited increased RR for various health conditions, with significant differences noted across racial groups for infertility, ovarian cysts, obesity, and respiratory diseases. Additionally, women with PCOS who were treated with PCOS-related medications showed a decrease in pain diagnoses following treatment. In conclusion, this study highlights the critical need to address pain in the diagnosis and management of PCOS due to its significant impact on patient health outcomes.

Polycystic ovary syndrome (PCOS) is associated with impaired adipose tissue physiology. Elevated brown adipose tissue (BAT) mass or activity has shown potential in the treatment of PCOS. In this study, we aimed to investigate whether BAT-derived exosomes (BAT-Exos), as potential biomarkers of BAT activity, exert similar benefits as BAT in the treatment of PCOS. PCOS was induced in female C57BL/6J mice orally administered 1 mg/kg of letrozole for 21 days. Subsequently, the animals underwent transplantation with BAT or administered BAT-Exos (200 μg) isolated from young healthy mice via the tail vein; healthy female mice were used as controls. The results indicate that BAT-Exos treatment significantly reduced body weight and improved insulin resistance in PCOS mice. In addition, BAT-Exos improved ovulation function by reversing the acyclicity of the estrous cycle, decreasing circulating luteinizing hormone and testosterone, recovering ovarian performance, and improving oocyte quality, leading to a higher pregnancy rate and litter size. Furthermore, western blotting revealed reduced expression of signal transducer and activator of transcription 3 (STAT3) and increased expression of glutathione peroxidase 4 (GPX4) in the ovaries of mice in the BAT-Exos group. To further explore the role of the STAT3/GPX4 signaling pathway in PCOS mice, we treated the mice with an intraperitoneal injection of 5 mg/kg stattic, a STAT3 inhibitor. Consistent with BAT-Exos treatment, the administration of stattic rescued letrozole-induced PCOS phenotypes. These findings suggest that BAT-Exos treatment might be a potential therapeutic strategy for PCOS and that the STAT3/GPX4 signaling pathway is a critical therapeutic target for PCOS.

We aimed to evaluate the risk of cardiovascular disease (CVD) in women with polycystic ovary syndrome (PCOS) and estimate the global incidence of PCOS-associated CVD.

We conducted a meta-analysis across five databases to evaluate the risk of CVD among women with PCOS. The global incidence of PCOS-associated CVD was calculated by a population attributable fraction modelling using the pooled risk ratio (RR), PCOS prevalence, CVD incidence number, and age-standardized rate (ASIR), from the Global Burden of Diseases 2019. An estimated annual percentage change (EAPC) was used to assess the temporal trend of PCOS-associated CVD. The risk of CVD was significantly increased in women with PCOS for an all-age group (pooled RR 1.51, 95% confidence interval 1.36-1.69) and 10- to 54-year-olds (1.37, 1.17-1.59). Globally, from 1990 to 2019, the PCOS-associated CVD cases in women across the all-age group has raised from 102 530 to 235 560. The most affected regions were East Asia and the Pacific (108 430, 66 090-166 150) in 2019. South Asia has the highest increase trend of PCOS-associated CVD ASIRs (EAPC 2.61%, 2.49-2.73). The annual increase in ASIR in PCOS-CVD incidence for the 10-54 age group (EAPC 0.49%, 0.41-0.56) is faster than that of the all-age group (0.34, 0.27-0.42). The middle- or low-middle sociodemographic index countries experienced higher increase trend of CVD due to PCOS in the past 30 years.

Women with PCOS have a significantly increased risk of CVD. Efficient measures to enhance its prevention and treatment are important for regions with a high PCOS-associated CVD burden, especially premature CVD in women under 55 years.

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder in women associated with increased cardiovascular risk. Cinnamon, a Chinese herbal medicine, is known for its anti-inflammatory and insulin-sensitizing properties, making it a potential therapeutic agent for PCOS-related cardiovascular complications. This systematic review and meta-analysis aimed to assess the impact of cinnamon supplementation on cardiovascular risk markers in women diagnosed with PCOS.

Twelve randomized controlled trials (RCTs) were included in the analysis. The primary outcomes assessed were body weight, insulin resistance measured by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and fasting blood sugar (FBS).

The meta-analysis revealed a statistically significant effect of cinnamon on reducing weight. Under the random-effects model, the pooled weighted mean difference (WMD) was -0.47 kg (95 % CI: -0.80 to -0.15, p < 0.001; I2 = 0.0 %). There was also a beneficial impact on insulin resistance, with reduced HOMA-IR scores following cinnamon supplementation (SMD=0.5015, 95 % CI: 0.2496 to 0.7533, p < 0.0001). Additionally, there was a significant improvement in FBS levels (pooled WMD: -7.72 mg/dL, 95 % CI: -12.33 to -3.12, p < 0.001; I2 = 91.3 %). The meta-analysis indicated a tendency towards reduced total cholesterol (WMD: -11.12 mg/dL, 95 % CI: -19.06 to -3.18, p = 0.01; I2 = 0.0 %) and LDL levels (WMD: -11.11 mg/dL, 95 % CI: -18.22 to -4.00, p < 0.01; I2 = 0.0 %) following cinnamon intervention. Substantial heterogeneity was observed among the studies, indicating the need for further research with larger sample sizes and standardized methodologies.

Cinnamon supplementation demonstrates promising effects on body weight, blood sugar, total cholesterol, LDL, and insulin resistance in women with PCOS, indicating its potential in mitigating cardiovascular risk factors associated with this condition.

In our study, we aimed to investigate the Achilles tendon thickness (ATT) and asprosin levels in patients with polycystic ovary syndrome (PCOS) and to evaluate the relationship of these parameters, which may be related to cardio-metabolic diseases.

In our prospective cross-sectional study, 45 female patients with PCOS and 30 female healthy individuals similar in age were included. Serum dehydroepiandrosterone sulfate (DHEAS), total testosterone, anti-Müllerian hormone (AMH) and asprosin levels were measured using appropriate kits and homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio was calculated. ATT measurements were performed by two radiologists using a high-resolution ultrasound doppler system.

Serum DHEAS, total testosterone, AMH and asprosin levels, HOMA-IR value, LF/FSH ratio, and ATT values were higher in patients with PCOS compared to healthy controls. Correlation analysis was performed between ATT and other parameters in patients with PCOS. In univariate analysis, parameters associated with ATT were detected as asprosin, DHEAS and AMH. In the linear regression analysis performed with significant parameters, asprosin and DHEAS levels were found to be associated with ATT.

ATT values and serum asprosin levels were found to be significantly increased in patients with PCOS, and there is a very close positive relationship between ATT and serum asprosin levels. For this reason, it was thought that ATT measurement could be a cheap, simple and non-invasive monitoring parameter that can be used in the routine cardiometabolic follow-up of patients with PCOS.

Zishen Qingre Lishi Huayu recipe (ZQLHR) has shown significant therapeutic effects in treating sex hormone levels and follicular developmental disorders in patients with polycystic ovary syndrome (PCOS). However, little is known about the potential mechanisms of its treatment.

Dehydroepiandrosterone and a high-fat diet induced the PCOS model rat. The serum of rats was collected to detect the levels of sex hormones and inflammatory cytokines by enzyme-linked immunosorbent assay, and the ovaries were collected for ovarian histopathology and qPCR assay to detect the levels of inflammatory cytokines in ovarian tissues. Granulosa cells (GCs) were collected for western blot assay to detect of IL-1β, IL-6R, and LOX protein expression levels.

ZQLHR could reduce body weight, regulate estrous cycles, and improve serum sex hormone levels, follicular development, and insulin resistance (IR) in PCOS model rats. In addition, ZQLHR treatment improved the levels of inflammatory cytokines in serum and ovary, and regulated the protein expression of IL-6R, IL-1β, and LOX in GCs of PCOS model rats. The results showed that the HOMA-IR index increased with the increasing levels of IL-6, IL-1β, and CRP, and decreased with the increased IL-10.

This study reveals that the treatment of endocrine disorders and ovulation disorders in PCOS with ZQLHR may be closely related to the improvement of systemic and ovarian inflammation in PCOS patients, as well as the inhibition of IL-6R, IL-1β, and LOX expression in GCs, which reemphasizes the role of reducing chronic inflammatory states in the treatment of PCOS. Moreover, this study reemphasizes the correlation between multiple inflammatory mediators and IR.

The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with in vitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), μmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.