Search

Background Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice. Objective To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS. Methods An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology. Results A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration. Conclusions The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of NOD-like receptor protein 3 （NLRP3） inflammasome and its relationship with granulosa cell apoptosis in patients with polycystic ovary syndrome （PCOS）. Methods: Follicular fluid and ovarian granulosa cells were collected from 17 PCOS patients（ PCOS group） and 20 non-PCOS patients（ control group）, and the expression levels of proinflammatory factor, TNF-α, IL-1β and IL-18 in follicular fluid were detected by ELISA. RT-PCR and Western blot were used to detect NLRP3 mRNA and NLRP3 inflammasome associated protein NLRP3, ASC and cleaved caspase-1 and autophagy related protein LC3-Ⅱ/LC3-Ⅰ and p62 expression level in granulosa cells. TUNEL assay was used to detect the apoptotic level of granulosa cells in both groups. NLRP3 silenced siRNA （si-NLRP3） and negative control sequence （si-NC） were transfected into human ovarian cancer granulosa cell line KGN cells by siRNA interference technique in vitro. TNF-α was used to simulate PCOS-related cell damage. KGN cells were divided into 4 groups according to different treatment methods: Ctrl group, TNF- α group, TNF- α+si-NLRP3 group and TNF-α+si-NC group. The levels of DHEA, testosterone, IL-1β and IL-18 in supernatant were detected by ELISA. TUNEL assay was used to detect the apoptosis level of KGN cells. The LC3-Ⅱ/LC3-Ⅰ and p62, NLRP3, ASC and cleaved caspase-1 protein expression levels, and NF-κB p-p65 level（ NF-κB p-p65/NF-κB p65） in KGN cells were detected by Western blot. Results: Compared with control group, the concentration of TNF-α, IL-1β, and IL-18 in follicular fluid of PCOS patients, and LC3-Ⅱ/LC3-Ⅰ, NLRP3 mRNA and the protein expression of NLRP3, ASC, and cleaved caspase-1 in granulosa cells of and apoptosis were significantly increased （P< 0.05 or P<0.01）, while the protein expression of p62 was significantly decreased （P<0.01）. Compared with Ctrl group, the levels of DHEA, testosterone, IL-1β and IL-18 in supernatant of TNF-α group, TNF-α+si-NC group, and TNF-α+si-NLRP3 group, and LC3- Ⅱ/LC3-Ⅰ, ASC and cleaved caspase-1 protein expression, and the level of NF-κB p-p65 and apoptosis were significantly increased （P<0.05 or P<0.01）, while p62 protein was significantly decreased （P<0.01）. NLRP3 was significantly decreased except in TNF-α+ si-NLRP3 group（ P<0.01）, while in the TNF-α group and TNF-α+si-NC group was significantly increased（ P<0.01）. However, compared with TNF-α group, the above indexes in TNF-α+si-NLRP3 group were significantly decreased （P<0.05）, and TNF-α+si-NC group had no significant change （P>0.05）. Conclusion: The over-activated NLRP3 inflammasome in granulosa cells may promote cell inflammatory injury and autophagy apoptosis in PCOS patients through NF-κB pathway. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a condition resulting from the interaction between environmental factors and hereditary components, profoundly affecting offspring development. Although the etiology of this disease remains unclear, aberrant in utero androgen exposure is considered one of the pivotal pathogenic factors. Herein, we demonstrate the intergenerational inheritance of PCOS-like phenotypes in F2 female offspring through F1 males caused by maternal testosterone exposure in F0 mice. We found impaired serum hormone expression and reproductive system development in prenatal testosterone-treated F1 male and F2 female mice (PTF1 and PTF2). In addition, downregulated N6-methyladenosine (m6A) methyltransferase and binding proteins induced mRNA hypomethylation in the PTF1 testis, including frizzled-6 (Fzd6). In the PTF2 ovary, decreased FZD6 protein expression inhibited the mammalian target of rapamycin (mTOR) signaling pathway and activated Forkhead box O3 (FoxO3) phosphorylation, which led to impaired follicular development. These data indicate that epigenetic modification of the mTOR signaling pathway could be involved in the intergenerational inheritance of maternal testosterone exposureinduced impairments in the PTF2 ovary through male PTF1 mice. [ABSTRACT FROM AUTHOR]

Alzheimer disease, the leading cause of dementia, and polycystic ovary syndrome, one of the most prevalent female endocrine disorders, appear to be unrelated conditions. However, studies show that both disease entities have common risk factors, and the amount of certain protein marker of neurodegeneration is increased in PCOS. Reports on the pathomechanism of both diseases point to the possibility of common denominators linking them. Dysregulation of the kynurenine pathway, insulin resistance, and impairment of the hypothalamic-pituitary-gonadal axis, which are correlated with amyloid-beta aggregation are these common areas. This article discusses the relationship between Alzheimer disease and polycystic ovary syndrome, with a particular focus on the role of disorders of tryptophan metabolism in both conditions. Based on a review of the available literature, we concluded that systemic changes occurring in PCOS influence the increased risk of neurodegeneration. [ABSTRACT FROM AUTHOR]

Purpose: PCOS and endometriosis are independent risk factors for perinatal outcomes. Little research has evaluated the concomitant effects of these conditions, nor have studies been conducted on a population database. We sought to identify the pregnancy, delivery, and neonatal outcomes in women with polycystic ovary syndrome (PCOS) and endometriosis vs. PCOS without endometriosis. Methods: A retrospective population-based cohort study was performed extracting data using ICD-9 codes from the HCUP-NIS Database from 2004 to 2014. Endometriosis in women with PCOS represented the study group (n = 163), and the remaining PCOS, non-endometriosis patients constituted the reference group (n = 14,719). Subjects were included once per delivery. Demographics were compared using chi-squared tests. Confounding effects in pregnancy outcomes were controlled using binary logistic regression analysis. Results: Concomitant endometriosis and PCOS patients were more likely to be white (88.5% vs.71.0%, p < 0.001), with BMI < 30 kg/m2 (87.1% vs.77.8%, p < 0.004) and from lower income quartiles (27.1% vs.17.1%, p < 0.017) when compared to PCOS without endometriosis. Comparing pregnancy complication rates, placental abruption (p < 0.018, aOR 3.01, 95% CI 1.21–7.50), Cesarean section (p < 0.003, aOR 1.75, 95% CI 1.21–2.53), deep venous thromboses (p < 0.002, aOR 74.31, 95% CI 4.57–1209.21), and venous thromboembolic events (p < 0.031, aOR 10.40, 95% CI 1.24–87.37), were increased in the study group compared to the reference group. Conclusion: Women with PCOS and endometriosis were more likely to be white, of lower socioeconomic status, lean, and experience abruptio-placenta, cesarean deliveries, and venous thromboembolisms. Since little was previously known about the combined outcomes of PCOS and endometriosis, it is difficult to counsel patients on risks. Our findings can help clinicians manage pregnant PCOS patients with endometriosis to minimize complications such as abruptio placenta and VTE. [ABSTRACT FROM AUTHOR]

Background/Objectives: Temporomandibular dysfunction syndrome consists of several disorders of the masticatory system, namely those of the muscles, the joint itself, as well as the dental and periodontal system. This syndrome is often characterized by pain and an inability to perform functions within the dental–maxillary apparatus, which creates a certain degree of disability in patients. Women are more susceptible to this syndrome than men and hormonal factors, particularly estrogen, are central to its etiology and physiopathology. Methods: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Embase, and Web of Science databases regarding articles published from January 2008 to December 2023. Two authors conducted searches in the mentioned databases based on a pre-established search strategy using agreed-upon keywords. Additionally, each review author performed the selection process of eligible studies based on established inclusion criteria. The Newcastle–Ottawa scale and Risk of Bias tool 2 were used to assess each article for its methodological quality. Results: Of the 1030 records found in the four bibliographic databases, 22 studies were included in this review. Polymorphism in the alpha estrogen receptor appears to be significantly more prevalent in women with temporomandibular dysfunction, suggesting a genetic predisposition. There is a significant role of estrogen in the physiopathology of TMD-related pain. Women with polycystic ovary syndrome (PCOS) have a significantly higher incidence of TMD, accompanied by elevated inflammatory factors and decreased progesterone levels. In premenopausal women, there is scientific relevance to the association between beta-estradiol levels and TMD development and progression. The effects of estrogen hormones on temporomandibular dysfunction remain highly debated and challenging. Conclusions: These findings emphasize the importance of considering hormonal factors, genetic predisposition, and reproductive life stages in understanding and managing temporomandibular dysfunction. Further research is needed to elucidate the specific mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disorder whose etiology is not well understood and affecting 9–18% of women in reproductive age. We investigated the protective effects of phloretin against the PCOS, induced Bisphenol A (BPA) on prepubertal rat ovaries. This study started on female rats on the postnatal 28th day via subcutaneous injection by dissolving the compounds in corn oil at 30 min intervals, starting with phloretin, and followed by BPA. The dose of BPA was 50 mg/kg/day, and the doses of phloretin were 0.5, 5, and 50 mg/kg/day. Treatments were administered every day for 15 days. Likewise corn oil, BPA and testosterone propionate were given by the same way. BPA exposed groups, it has been observed that there are many cystic follicles in the ovary and their morphology has changed. Similarly, prolonged diestrus phases was observed in the smear cycle. The CYP11A1 and CYP17A enzymes stained intensively on the BPA group whereas these enzymes were stained weakly in the BPA + 5 and 50 mg/kg phloretin groups. In PCOS, induced by BPA, the cystic follicles were recorded on the ovaries whereas it was decreased in the BPA + phloretin groups. Prepubertal exposure to BPA was associated with decreased serum luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels, increased estrogen (ERRα) and dihydrotestosterone (DHT) levels in testosterone propiyonat and BPA + phloretin (0.5 mg/kg/day) groups. In conclusion, in rat model, phloretin has positive effects against BPA induced polycystic ovarian syndrome, also it caused positive effects on ovarian tissue and hormone secretion. [ABSTRACT FROM AUTHOR]

Purpose: To examine the pattern of kisspeptin expression throughout the menstrual cycle in polycystic ovary syndrome (PCOS) patients under the ovulation induction and identify any possible associations with early pregnancy. Materials and methods: A prospective cohort of 80 PCOS women who expressed the desire for fertility was enrolled in this study. All of them received the ovulation induction by using letrozole. Levels of kisspeptin, luteinizing hormone (LH), and estradiol (E2) were measured at three different time points during menstruation. The early pregnancy rate was recorded for the study participants after three ovulation cycles. Results: Kisspeptin levels varied regularly during the menstrual cycle, reaching a peak on the day of hCG injection and decreasing after ovulation. There was no significant correlation between kisspeptin and LH levels. Basal kisspeptin levels decreased after letrozole treatment without a significant difference while LH and E2 levels decreased significantly. PCOS participants who became pregnant early had higher basal kisspeptin levels compared to non-pregnant PCOS patients, which had a significant difference (P = 0.006). And the average basal kisspeptin level in pregnant patients was 2293.0 ± 398.7 pg/ml, with a 95% confidence interval of 1511.5–3074.5 pg/ml. Conclusion: Kisspeptin levels in PCOS women undergoing ovulation induction showed a regular variation, which was similar with the healthy women reported in previous studies. The use of LE may result in PCOS endocrine improvement and fertility achievement. In a certain range, kisspeptin might be a potential predictor for early pregnancy in PCOS patients as people with slightly higher basal kisspeptin levels seemed more likely to be pregnant. [ABSTRACT FROM AUTHOR]

Research often suggests that online support groups validate their members’ experiences, but feminists and sociologists have argued that they may also embrace individualistic or biomedical perspectives. Interviews with women with polycystic ovary syndrome (PCOS), associated with weight gain, highlighted that reading other women’s painful experiences in a Facebook support group helped them to accept their bodies, but that the group was replete with unwanted weight loss advice. Making sense of these contradictions this article makes three contributions. First, the findings illustrate that the way in which online support groups validate their members’ experiences may be more subterfuge and contradictory than previously thought. Second, the observations contribute to feminist research on online body positivity, as the women articulated an ambiguous desire to let themselves be rather than sought to become either traditionally thin and beautiful or in a popular feminist spirit confidently big and beautiful. Following from this observation, the article draws on and contributes to feminist media studies discussions on post- and popular feminism, suggesting that the women articulated a barely articulable emerging structure of feeling of yearning to let go of self-transformation, which pervades official health advice, support groups and much feminist content online. [ABSTRACT FROM AUTHOR]

Aim: Exclusion of polycystic ovarian morphology (PCOM) from the diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been proposed. We analyzed the profiles of adolescent women with suspected PCOS based on the Japan Society of Obstetrics and Gynecology (JSOG) diagnostic and Rotterdam criteria, excluding those with PCOM. Methods: Thirteen‐ to twenty‐one‐year‐old women with suspected or confirmed diagnosis of PCOS according to the JSOG and Rotterdam criteria were included in this study. Patient characteristics such as hormone levels and body mass index (BMI) were compared between the groups. Correlations between BMI and testosterone, and BMI and time to diagnosis were also analyzed. Results: Twenty‐nine patients were diagnosed with adolescent PCOS according to the JSOG criteria, and 11 patients according to the Rotterdam criteria after excluding the patients fulfilling the PCOM criteria. Serum testosterone levels were significantly higher in adolescents diagnosed with PCOS using the Rotterdam criteria than in those diagnosed using the JSOG criteria (p < 0.001). The obese group had significantly higher testosterone levels and a longer time from menarche to PCOS diagnosis. A positive correlation was observed between BMI and testosterone levels (r = 0.318, p = 0.014). Conclusion: Although adolescents with PCOS diagnosed using the Rotterdam criteria exhibited higher testosterone levels, which is a typical characteristic of this condition, the JSOG criteria may be useful for the early diagnosis of adolescent PCOS, including suspected cases. The differences between the two criteria may reflect the natural history of PCOS and its different reproductive and metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Aim: To establish cut‐off values for anti‐Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence‐Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria. Methods: Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut‐off values for AMH and AFC. Results: Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut‐off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20–29 and 30–39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut‐off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH. Conclusion: The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria. [ABSTRACT FROM AUTHOR]

PCOS is a heterogeneous, multifactorial endocrine disorder with a complex pathophysiology. It is a globally rising infertility disorder that affects a large percentage of women of reproductive age, with a relatively high prevalence of 8–13%. Genome-wide association studies have revealed associations of genetic variations with many diseases, including PCOS. The cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by TNF-α. Therefore, this study aimed to investigate the association of TNF-α, CCR5-delta32, and CXCR2 gene variations with PCOS. Methodology: In this case control study, we used amplification-refractory mutation system (ARMS)-PCR to detect and determine the presence of the polymorphic variants TNF-α, CCR5-delta32, and CXCR2 in the study subjects. These gene polymorphs may serve as critical candidate gene variants in PCOS pathogenesis and therapeutics. Results: The case–control study's findings revealed that the majority of the biochemical and endocrine serum biomarkers examined in the investigation—including lipids (LDL, HDL, and cholesterol), T2DM markers (fasting glucose, free insulin, and HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone)—exhibited statistically significant changes in PCOS patients. The distributions of TNF-α (rs1800629), CCR5-delta32, and CXCR2 (rs2230054) genotypes analyzed within PCOS patients and healthy controls in the considered population were significant (p < 0.05). The heterozygosity of CXCR2-CA, TNF-α GA, and CCR5(WT+Δ32*) genotypes was significantly associated with PCOS susceptibility, with high OR and p < 0.05 in the codominant model. Similarly, the A allele of the TNF-α and CXCR2 genes, along with the CCR5Δ32*(mutant) allele, was significantly associated with PCOS susceptibility, with high OR and p < 0.05. Likewise, the CXCR2 (CA+AA) vs CC genotype was associated with increased susceptibility to PCOS, with OR 2.25, p < 0.032. Conclusions: Our study concludes that TNF-α rs1800629G>A, CXCR2-rs2230054C>T, and CCR5-Delta32 rs333 are potential loci for developing PCOS in the Tabuk population. These findings might eventually be useful in identifying and classifying those who are at risk for PCOS. To validate these results, it is advised that further longitudinal studies be conducted in diverse ethnic populations and with larger sample sizes. [ABSTRACT FROM AUTHOR]

Objective(s): Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice. Materials and Methods: Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. In vitro fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries. Results: PCOS-elevated concentration of LH and Testosterone was significantly (P<0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%. Conclusion: These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders. [ABSTRACT FROM AUTHOR]

Objective(s): Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of Δ tetrahydrocannabinol-9 (THC) on PCOS has not been evaluated. Therefore, this study aimed to investigate the immunomodulatory effects of THC in an animal model of PCOS. Materials and Methods: Twenty female Sprague-Dawley rats, aged 4 weeks, were divided into four groups. The control group received a normal diet, the sham group received a vehicle (carboxymethyl cellulose), the PCOS group received a high-fat diet (HFD) for 16 weeks followed by letrozole for 4 weeks, and the THC group received an HFD for 16 weeks followed by letrozole+THC (0.02 mg/kg) for 4 weeks. Results: The PCOS animals exhibited significantly higher levels of testosterone, insulin, triglycerides, and total cholesterol, along with elevated inflammatory and oxidative stress markers compared to the control group. Flow cytometry and real-time PCR analysis revealed an increase in M1 macrophage markers and a decrease in M2 macrophage markers compared to the control group. However, the administration of a low dose of THC mitigated these disturbances. Conclusion: Low-dose THC improved inflammatory responses and shifted the balance of M1/M2 macrophage markers towards M2 macrophages in the animal model of PCOS. [ABSTRACT FROM AUTHOR]

Introduction: Breastfeeding represents an important opportunity to optimize health outcomes for both mother and infant, particularly in the context of maternal metabolic conditions such as diabetes and polycystic ovary syndrome. However, evidence suggests that women affected by these conditions breastfeed at reduced rates and durations. Our aim was to use the large, prospective, community‐based Australian Longitudinal Study on Women's Health (ALSWH) to conduct an in‐depth exploratory analysis of breastfeeding outcomes in Australian women affected by key maternal metabolic conditions. Material and Methods: Data from 12 920 pregnancies to 5605 women from the 1973–1978 birth cohort of the ALSWH were examined. Univariable and multivariable regression using generalized estimating equation models were applied to assess breastfeeding initiation and duration (outcome measures) in relation to key self‐reported maternal metabolic diagnoses (pre‐gestational type 1 and type 2 diabetes, gestational diabetes, and polycystic ovary syndrome; main explanatory variables). Key sociodemographic and clinical covariates were also considered. Results: Results showed no significant association between specific maternal metabolic diagnoses (pre‐gestational or gestational diabetes, or polycystic ovary syndrome) and breastfeeding outcomes. However, maternal body mass index emerged as a key predictor of suboptimal breastfeeding outcomes. Pregnancies affected by maternal obesity were associated with a 2.1‐fold increase in the odds of not initiating breastfeeding, after adjusting for other key variables (95% CI 1.67 to 2.60, p < 0.01). Maternal overweight and obesity were, respectively, associated with an adjusted 1.4‐fold (95% CI 1.20 to 1.55, p < 0.01) and 1.8‐fold increase (95% CI 1.60 to 2.10, p < 0.01) in the odds of a breastfeeding duration less than 6 months. Conclusions: Maternal obesity, rather than any specific maternal metabolic condition, appears to be a key predictor of breastfeeding outcomes in Australian women. [ABSTRACT FROM AUTHOR]

Introduction: The knowledge regarding eating behavior and disorders in women with polycystic ovary syndrome (PCOS) and severe obesity is limited. This study aimed to assess eating behavior and lifestyle factors in women with severe obesity (BMI ≥35 kg/m2), with and without PCOS, and the effect of weight loss on these behaviors. Material and Methods: A prospective clinical trial with participants screened for PCOS using National Institutes of Health criteria. Participants completed the Food Frequency Questionnaire, International Physical Activity Questionnaire, Three‐Factor Eating Questionnaire, and Questionnaire of Eating and Weight Patterns‐revised, and were evaluated regarding binge eating disorder using DSM‐5 criteria before and after a 12‐month weight loss intervention. Clinicaltrials.gov: NCT01319162. Results: 246 women were included (PCOS n = 63, age 33.0 ± 8.4, BMI 39.9 ± 4.7; non‐PCOS n = 183, age 37.7 ± 8.7, BMI 39.6 ± 4.3). Women with PCOS showed elevated baseline scores in cognitive restraint eating (50.0 [33.3–63.2]) compared to women without PCOS (38.9 [27.8–55.6]; p = 0.012). No differences were observed between groups in emotional and uncontrolled eating. In both groups, cognitive restraint eating was negatively correlated with energy intake (PCOS: r = −0.315, p < 0.05; non‐PCOS: r = −0.214, p < 0.001), while uncontrolled eating displayed a positive correlation with energy intake (PCOS: r = 0.263, p = 0.05; non‐PCOS: r = 0.402, p < 0.001). A positive correlation was found between emotional eating and energy intake only in women without PCOS (r = 0.400, p < 0.001). Baseline self‐reported energy intake and physical activity did not differ between groups. At 12‐month follow‐up, women with PCOS reported reduced fat intake. Women without PCOS reported reduced energy intake, carbohydrates and sugar, increased protein, reduced scores for emotional and uncontrolled eating, and heightened scores for cognitive restraint eating. Comparing changes from baseline to follow‐up, differences were found between groups in cognitive restraint, intake of fat, carbohydrates, and sugar. The mean weight loss was 12–14 kg, with no between‐group difference (p = 0.616). Conclusions: Women with severe obesity and PCOS showed elevated cognitive restraint eating behaviors compared to women without PCOS. Although significant weight loss was seen in both groups, alterations in eating behavior more favorable for weight loss were only seen in women without PCOS. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. Material and Methods: This work was a prospective cross‐sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. Results: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03–8.81) and prediabetes (OR: 3.94; 95% CI: 1.01–15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16–5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. Conclusions: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)‐induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle‐stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle‐stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone‐binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites–brain–ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin‐1), lipopolysaccharides/Toll‐like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. Key points: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS).Adropin regulated the ovarian steroidogenesis and sex hormone‐binding globulin in PCOS.Adropin improved lipid profile and decreased insulin resistance in PCOS.Adropin modulated the components of the gut–brain–ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS.Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll‐like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS. [ABSTRACT FROM AUTHOR]

Research question: In a randomized, triple-blind, placebo-controlled clinical trial (RCT), we investigated the effect of astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and assisted reproductive technology (ART) outcomes in 44 infertile Polycystic Ovary Syndrome (PCOS) patients. Design: Patients with PCOS were randomly divided into two groups. The intervention group received 6 mg AST, and the control group received placebo daily for 8 weeks. Blood samples were obtained from all patients before and after intervention and follicular fluid (FF) was collected during the ART procedure. Interleukin (IL) ‐6, IL‐1β were evaluated from serum samples and FF and OS markers (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD], and reactive oxygen species [ROS]) were measured from FF. The groups were compared for ART outcomes as well. Results: A significant decrease in IL-6 and IL-1β concentrations (both, P = < 0.01) serum levels was found following AST treatment. FF cytokine levels and OS markers did not differ significantly between the groups. Reproductive outcomes, including the number of oocytes retrieved (P = 0.01), the MII oocyte count (P = 0.007), oocyte maturity rate (MII %) (P = 0.02) and number of frozen embryos (P = 0.03) significantly improved after intervention. No significant differences were found in chemical, clinical and multiple pregnancies between the groups. Conclusions: AST pretreatment may modify inflammation and improve ART outcomes in PCOS infertile patients. Further investigations are recommended to verify these findings. [ABSTRACT FROM AUTHOR]

The main purpose of this article is to explore the relationship between autophagy and the pathological mechanism of PCOS, and to find potential therapeutic methods that can alleviate the pathological mechanism of PCOS by targeting autophagy. Relevant literatures were searched in the following databases, including: PubMed, MEDLINE, Web of Science, Scopus. The search terms were "autophagy", "PCOS", "polycystic ovary syndrome", "ovulation", "hyperandrogenemia", "insulin resistance", "inflammatory state", "circadian rhythm" and "treatment", which were combined according to the retrieval methods of different databases. Through analysis, we uncovered that abnormal levels of autophagy were closely related to abnormal ovulation, insulin resistance, hyperandrogenemia, and low-grade inflammation in patients with PCOS. Lifestyle intervention, melatonin, vitamin D, and probiotics, etc. were able to improve the pathological mechanism of PCOS via targeting autophagy. In conclusion, autophagy disorder is a key pathological mechanism in PCOS and is also a potential target for drug development and design. [ABSTRACT FROM AUTHOR]

Research question: Theca interna cells (TICs) are an indispensable cell source for ovarian follicle development and steroidogenesis. Recent studies have identified theca stem cells (TSCs) in both humans and animals. Interestingly, TSCs express mesenchymal stem cell (MSC)-related markers and can differentiate into mesenchymal lineages. MSCs are promising for tissue engineering and regenerative medicine due to their self-renewal and differentiation abilities. Therefore, this study investigated the potential origin of TICs from MSCs. Design: Whole ovaries from postmenopausal organ donors were obtained, and their cortex was cryopreserved prior to the isolation of stromal cells. These isolated cells were differentiated in vitro to TICs using cell media enriched with various growth factors and hormones. Immunocytochemistry, an enzyme-linked immunosorbent assay, flow cytometry, and reverse transcription–quantitative polymerase chain were employed at different timepoints. Data were analyzed using one-way ANOVA. Results: Immunocytochemistry showed an increase in TIC markers from day 0 to day 8 and a significant rise in MSC-like markers on day 2. This corresponds with rising androstenedione levels from day 2 to day 13. Flow cytometry identified a decreasing MSC-like cell population from day 2 onwards. The CD13+ cell population and its gene expression increased significantly over time. NGFR and PDGFRA expression was induced on days 0 and 2, respectively, compared to day 13. Conclusions: This study offers insights into MSC-like cells as the potential origin of TICs. Differentiating TICs from these widely accessible MSCs holds potential significance for toxicity studies and investigating TIC-related disorders like polycystic ovary syndrome (PCOS). [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro‐inflammatory cytokine interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF‐κB) subunit p65 by DHEA and weakened the transcriptional activity of NF‐κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF‐κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2‐Foxo1‐GSH‐NF‐κB pathway. [ABSTRACT FROM AUTHOR]

Introduction: In humans, prenatal androgen excess can lead to a broad spectrum of pathologies in adulthood, including polycystic ovary syndrome (PCOS). Women with PCOS present a variety of reproductive and metabolic disturbances and they also face increased risk to develop neuropsychiatric disorders such as depression and anxiety. Despite the high prevalence, the cause of depressive and anxiety symptoms is not fully elucidated. The use of androgenized ewe models can provide valuable insights into the pathogenesis of PCOS, as they closely mimic the reproductive, neuroendocrine, and metabolic characteristics observed in women with this condition. Method: We studied the impact of prenatal exposure to testosterone propionate on cognitive and behavioral performances of Ile-de-France ewes, using a plethora of behavioral tests for anxiety and cognitive performances. Results: Our findings indicate that prenatal androgenized ewes exhibit markedly elevated levels of anxiety-like behavior compared to control animals, while showing no discernible differences in cognitive performance. Conclusion: These discoveries offer novel perspectives on how maternal androgen excess contributes to anxiogenic effects in PCOS preclinical models, underscoring the ewe's significance as a model for conducting mechanistic studies to unravel the physiological and molecular aspects of anxiety. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? SUMMARY ANSWER A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. WHAT IS KNOWN ALREADY The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. STUDY DESIGN, SIZE, DURATION This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0–14.8), 9.8 (5.1–15.1), and 6.0 (2.0–10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. MAIN RESULTS AND THE ROLE OF CHANCE The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98–4.60) in Denmark, 3.40 (3.11–3.74) in Finland, and 5.68 (5.20–6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40–5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32–3.51). LIMITATIONS, REASONS FOR CAUTION Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. STUDY FUNDING/COMPETING INTEREST(S) Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is resting energy expenditure (REE) altered in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Women with PCOS have a reduction in REE, when corrected for fat-free mass, independent of PCOS clinical phenotypes and BMI categories. WHAT IS KNOWN ALREADY Obesity is an important issue in women with PCOS, in terms of frequency and pathophysiological implications. It has been hypothesized that obesity may be favoured by alterations in REE, but the studies have been limited and conflicting. STUDY DESIGN, SIZE, DURATION This case–control study was a comparison of 266 women with PCOS and 51 healthy controls, recruited in the Verona 3P study from 2010 to 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with PCOS diagnosed by the Rotterdam criteria, with normal thyroid function and no interfering medications, were referred to the outpatient clinic of a tertiary care centre of endocrinology and metabolism for a measurement of REE. Healthy controls were recruited in the same period and submitted to the same procedure. In all subjects, REE was measured by indirect calorimetry and serum androgens were measured by LC-MS/MS. In women with PCOS, insulin sensitivity was assessed using the hyperinsulinemic–euglycemic clamp. MAIN RESULTS AND THE ROLE OF CHANCE REE was similar in women with PCOS and controls. However, REE corrected for fat-free mass (REE/FFM) was significantly lower in women with PCOS than in controls (31.8 ± 4.0 vs 35.4 ± 3.9 kcal/kgFFM·day, P  < 0.001). REE/FFM did not differ between normal-weight, overweight, or obese women with PCOS, and each of these subgroups showed lower REE/FFM values than controls. Reduced REE/FFM values were found in each phenotype of the syndrome. In multiple regression analysis, REE/FFM was independently associated with age and PCOS status, but not with fat mass. In PCOS women, REE/FFM was independently and directly associated with ovarian follicle number. LIMITATIONS, REASONS FOR CAUTION Limitations of the study are the cross-sectional design, which limits the causal inference of the results, and the unavailability of precise information about lifestyle factors, which may be potential confounders. Further prospective studies are needed to establish the importance of this phenomenon in contributing to the weight excess of PCOS. WIDER IMPLICATIONS OF THE FINDINGS A reduction of REE could potentially favour weight gain in women with PCOS and possibly contribute to the altered metabolic profile typical of this condition, even counteracting the therapeutic strategies aimed to reduce excess body fat in these women. Nevertheless, the presence of this abnormality in both obese/overweight and normal-weight patients suggests that other factors must play a role in this phenomenon. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by academic grants to PM from the University of Verona (FUR 2010-2022). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS), which is common among women of reproductive age, is characterized by low‐grade chronic inflammation and is associated with several health problems and dysbiosis. Kefir has been shown to have many beneficial health effects; however, its effect on PCOS is unknown. This study aimed to examine the effect of kefir on the intestinal microbiota and health outcomes in PCOS. In this intervention study, 17 women with PCOS consumed 250 mL/day of kefir (containing Lactobacillus kefiranofaciens subsp. kefiranofaciens, Lactobacillus kefiranofaciens subsp. kefirgranum, Lactobacillus kefiri, Lactobacillus acidophilus, Lactobacillus parakefiri, Lactobacillus bulgaricus, Lactobacillus reuteri, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus helveticus, Lactococcus lactis, Leuconostoc mesentereoides, Bifidobacterium bifidum, Streptococcus thermophilus, Kluyveromyces marxianus, Kluyveromyces lactis, Acetobacter pasteurianus, and Saccharomyces cerevisiae) for 8 weeks. Food consumption and physical activity records, anthropometrical measurements, quality of life, and fecal and blood samples were taken at the study's beginning and end. Quality of life in mental health (58.8 ± 15.08; 64.0 ± 15.23, respectively) and physical function (95.00 and 100.00, respectively) categories showed a significant increase after kefir intervention (p <.05). Additionally, Interleukin‐6 (IL‐6), one of the inflammatory cytokines, significantly decreased (174.00 and 109.10 ng/L, respectively) (p <.05). The intestinal barrier permeability was evaluated with zonulin, and no significant change was observed. Gut microbiota analysis showed that while the relative abundance of the class Bacilli and genus Lactococcus significantly increased, the genus Holdemania decreased with kefir consumption (p <.05). In conclusion, kefir appears to be beneficial for improving the microbiota and some health outcomes, like reducing inflammation and improving quality of life in PCOS. Therefore, kefir may be useful in the treatment of PCOS. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

• PCOS and hyperprolactinemia are well known to co-exist. • Metformin and cabergoline, can provide additional benefits when given together. • Prolactin levels along with other hormonal profile seems to get benefit from this combination. • BMI also exhibits positive responses to this combined therapy. Isntroduction. Polycystic ovary syndrome (PCOS) is a multifaceted endocrine-gynecological condition affecting a substantial number of women during their reproductive years. Metformin (MET) has been shown to improve ovarian function in PCOS-related conditions, while cabergoline is recognized for its powerful and sustained ability to reduce prolactin levels. This study investigates the potential impact of combining cabergoline with metformin while comparing it with metformin alone in the treatment of PCOS alongside hyperprolactinemia. To gather data, we searched PubMed, Google Scholar, ScienceDirect, and Cochrane Central. Eligible studies were randomized controlled trials involving patients with PCOS and hyperprolactinemia. Outcome measures included changes in the levels of prolactin, testosterone, DHEAS, BMI and menstrual irregularities. RevMan version 5.4 was used to analyze outcomes. This study incorporated three Randomized Controlled Trials (RCTs) involving 405 participants in total. Patients receiving a combination of metformin and cabergoline experienced significant reductions in prolactin and testosterone levels (p= <0.0001 and p=<0.0001, respectively). Conversely, alterations in DHEAS levels and BMI did not reach statistical significance (p = 0.19 and p = 0.71, respectively). Notably, women solely prescribed metformin exhibited significantly higher rates of menstrual irregularities compared to those receiving both metformin and cabergoline (p=<0.0001). Our analysis underscores the synergistic effect achieved by pairing metformin and cabergoline in patients with PCOS and hyperprolactinemia. However, we encountered only a restricted number of studies meeting our criteria. It is imperative to consistently assess the combined effects of metformin and cabergoline to gain deeper insights into their effectiveness in addressing PCOS and hyperprolactinemia. [ABSTRACT FROM AUTHOR]

• Population-level data on the relationship between PCOS and gynecologic cancers are limited and conflicting. • We analyzed the USA-based National Inpatient Sample data over 4 years (2016–2019) • PCOS is significantly associated with higher risk of endometrial cancer. • PCOS does not associate with higher risk of ovarian and cervical cancers. This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database. We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016–2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI). Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18–1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45–0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51–0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32–4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89–1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62–1.11], p = 0.218). This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers. [ABSTRACT FROM AUTHOR]

• A meta -analysis address the impact of insulin resistance on IVF/ICSI in PCOS women. • Insulin resistance reduces MII oocytes, total embryo and clinical pregnancy rate. • Insulin resistance leads to a higher rate of miscarriage. • In women with PCOS, insulin resistance had a negative impact on IVF/ICSI outcomes. To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta -analysis. The systematic review and meta -analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: −2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: −0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: −1.54 to −0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: −1. 78 to −0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group. In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary. [ABSTRACT FROM AUTHOR]

• Prevalence of endometriosis among pregnant patients increased by 24 % from 2016 to 2020. • Endometriosis during pregnancy was associated with placenta previa, cesarean delivery, maternal age of ≥30 years, prior pregnancy loss, PCOS, and anxiety disorders. • Endometriosis during pregnancy was associated with increased severe maternal morbidity at delivery. • Severe maternal morbidity indicators associated with endometriosis included thromboembolism, sepsis, and hysterectomy. To examine pregnancy characteristics and maternal morbidity at delivery among pregnant patients with a diagnosis of endometriosis. This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 17,796,365 hospital deliveries from 2016 to 2020, excluded adenomyosis and uterine myoma. The exposure was endometriosis diagnosis. Main outcome measures were clinical and pregnancy characteristics and severe maternal morbidity at delivery related to endometriosis, assessed with multivariable regression model. Endometriosis was diagnosed in 17,590 patients. The prevalence of endometriosis increased by 24 % from one in 1,191 patients in 2016 to one in 853 patients in 2020 (adjusted-odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.19–1.30). Clinical and pregnancy characteristics that had greater than two-fold association to endometriosis included polycystic ovary syndrome, placenta previa, cesarean delivery, maternal age of ≥30 years, prior pregnancy loss, and anxiety disorder. Pregnant patients with endometriosis were more likely to have the diagnosis of measured severe maternal morbidity during the index hospitalization for delivery (47.8 vs 17.3 per 1,000 deliveries, aOR 1.91, 95%CI 1.78–2.06); these associations were more prominent following vaginal (aOR 2.82, 95%CI 2.41–3.30) compared to cesarean (aOR 1.85, 95%CI 1.71–2.00) deliveries. Among the individual morbidity indicators, endometriosis was most strongly associated with thromboembolism (aOR 5.05, 95%CI 3.70–6.91), followed by sepsis (aOR 2.39, 95%CI 1.85–3.09) and hysterectomy (aOR 2.18, 95%CI 1.85–2.56). When stratified for endometriosis anatomical site, odds of thromboembolism was increased in endometriosis at distant site (aOR 9.10, 95%CI 3.76–22.02) and adnexa (aOR 7.37, 95%CI 4.43–12.28); odds of sepsis was most increased in endometriosis at multi-classifier locations (aOR 7.33, 95%CI 2.93–18.31) followed by pelvic peritoneum (aOR 5.54, 95%CI 2.95–10.40); and odds of hysterectomy exceeded three-fold in endometriosis at adnexa (aOR 3.00, 95%CI 2.30–3.90), distant site (aOR 5.36, 95%CI 3.48–8.24), and multi-classifier location (aOR 4.46, 95%CI 2.11–9.41). The results of this nationwide analysis suggest that pregnancy with endometriosis is uncommon but gradually increasing over time in the United States. The data also suggest that endometriosis during pregnancy is associated with increased risk of severe maternal morbidity at delivery, especially for thromboembolism, sepsis, and hysterectomy. These morbidity risks differed by the anatomical location of endometriosis. [ABSTRACT FROM AUTHOR]

This article discusses the dysbiosis of the oral-gut microbiome in patients with polycystic ovary syndrome (PCOS) and its implications for noninvasive diagnosis. PCOS is a common reproductive endocrine disorder that affects women of reproductive age. The study analyzed the oral and gut microbiome of PCOS patients and healthy controls and identified differences in microbial composition and functionality between the two groups. The findings suggest that the oral and gut microbiota may serve as potential predictive markers for PCOS diagnosis, and combining microbial indicators with clinical indices can optimize the accuracy of PCOS discrimination. [Extracted from the article]

Polycystic Ovary Syndrome (PCOS) is a multifaceted condition influenced by genetic, hormonal, and environmental factors. Among environmental factors, Bisphenol A (BPA)—a recognized endocrine disruptor—has been implicated in the development of PCOS. The study aimed to compare BPA levels in women diagnosed with PCOS with those in healthy controls, using the high-performance liquid chromatography (HPLC) technique. The study involved 80 women diagnosed with PCOS and 50 healthy control participants. Demographic and biochemical parameters were recorded, including age, Body Mass Index (BMI), and levels of testosterone, estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Dehydroepiandrosterone Sulfate (DHEA-S), Thyroid Stimulating Hormone (TSH), and Insulin Resistance as measured by the Homeostatic Model Assessment (HOMA-IR). Furthermore, BPA levels were measured using the HPLC technique. Women with PCOS exhibited significantly higher mean age and BMI compared to healthy controls (p = 0.01, p < 0.0001, respectively). Additionally, higher levels of testosterone (p = 0.04), LH (p = 0.03) and BPA (p < 0.0001) were observed in women with PCOS. However, estradiol, FSH, PRL, LH/FSH ratio, DHEA-S, and TSH levels were not significantly different between the two groups. HOMA-IR levels were not recorded for the control group. A notable positive relationship emerged between Bisphenol A and luteinizing hormone (LH) levels (r = 0.23, p = 0.03), also significant negative correlation appeared between Bisphenol A and thyroid-stimulating hormone (TSH) levels. This study found that women with PCOS have elevated BPA levels compared with healthy controls, showing a need for further research on the relationship between BPA exposure and the development of PCOS. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder. Atrial natriuretic peptide (ANP) is a risk factor for PCOS. Corin protein has an essential role in ANP synthesis. This study aimed to evaluate corin as a sensitive biomarker for PCOS. Materials and Methods: A case-control study was conducted with 70 PCOS patients and 70 healthy females. Plasma Corin levels were quantified using enzyme-linked immunosorbent assay. Results: The median plasma corin levels in PCOS patients and controls were 1785 and 822.5 pg/mL, respectively. Plasma corin levels were significantly elevated in PCOS patients than in the controls (p < 0.001). The optimal cut-off value was set at 1186 pg/mL. The sensitivity and specificity of Corin were 100% and 97.1%, respectively. Plasma corin levels were surrogate predictors for infertility in women with PCOS. It had an odds ratio of 5.9 (95% confidence interval: 1.1–32.7) (p = 0.04). Plasma corin levels were more highly detected in patients with PCOS than in the controls. Conclusion: Plasma corin level has reasonable diagnostic interpretation for PCOS. Corin appears as a worthy distinct predictor of infertility in PCOS women. Therefore, Corin may be a substantial biomarker for PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS. [ABSTRACT FROM AUTHOR]

Observational investigations recommend that mineral supplements were associated with a higher risk of polycystic ovary syndrome (PCOS) and its risk factors (insulin resistance, hyperandrogenism, and obesity), but the relationship with risk of PCOS, hyperandrogenism, obesity, and insulin resistance was unclear. This study was to investigate the potential causal impact of genetically predicted levels of magnesium (Mg), calcium (Ca), selenium (Se), zinc (Zn), iron (Fe), and omega-3 (ω-3) on polycystic ovary syndrome (PCOS) and its associated risk factors. A two-sample Mendelian randomization (MR) analysis was conducted. The genetic variations obtained from GWAS of individuals with European ancestry were found to be associated with the genetically predicted levels of Ca, Mg, Zn, Se, Fe, or ω-3. The data obtained from the FinnGen Consortium and MAGIC were utilized for the outcome of GWAS. The study found that there was a correlation between genetically predicted higher levels of Se and a reduced risk of insulin resistance, with a decrease of 2.2% according to random-effect IVW (OR 0.978, 95% CI 0.960–0.996, p = 0.015). The association between genetically determined mineral levels and PCOS was found to be limited, with an odds ratio (OR) ranging from 0.875 (95% CI: 0.637–1.202, p value = 0.411) for Ca. Limited scientific proof was found for the efficacy of other genetically determined mineral levels on hyperandrogenism, obesity, and insulin resistance. These findings suggested a causal relationship between genetically predicted higher levels of Se and a reduced risk of insulin resistance. Nonetheless, there is limited evidence supporting a causal association between various genetically determined mineral levels and the risk factors associated with PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is a common and frequently undiagnosed female endocrine disorder that is associated with diverse symptoms and features, and an increased risk of long-term chronic diseases such as type 2 diabetes and cardiovascular disease. Pharmacotherapy for polycystic ovary syndrome should be directed at the key concerns of the individual patient. The combined oral contraceptive pill or metformin may be prescribed for irregular periods. The combined oral contraceptive pill is preferred over antiandrogens for treatment of hirsutism and acne. Metformin is of benefit for reducing excess body weight and improving hormonal and metabolic outcomes in those with high metabolic risk (e.g. body mass index greater than 25 kg/m²). Inositol appears to have limited benefits for metabolic outcomes, although it is associated with fewer adverse effects than metformin. Modification of lifestyle factors is important as part of a holistic approach to managing polycystic ovary syndrome. Anti-obesity drugs may be considered for weight management in addition to lifestyle interventions. [ABSTRACT FROM AUTHOR]

Aim: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that affects the endocrine glands and reproductive processes in adolescent girls, potentially impacting their quality of life. This study aims to compare the quality of life between adolescent girls with PCOS and those without PCOS. The present study is an analytical cross-sectional study. It involved 12–18-year-old girls who were diagnosed with PCOS based on the Rotterdam criteria for the case group. An ordinal logistic regression model was employed to assess the impact of the studied variables on different levels of quality of life, and Odds Ratio (OR) values were determined for predictor variables. The findings of the study revealed that the control group had a significantly higher percentage of individuals with excellent quality of life (score 209–260) compared to the group with polycystic ovary syndrome (p<0.05). The results of the ordinal logistic regression analysis indicated that age variables (OR=0.64, CI 95 %; 0.44–0.93), menstrual disorders (OR=0.07, CI 95 %; 0.01–0.38), and micromastia (OR=0.03, CI 95 %; 0.004–0.34) were identified as factors influencing the quality of life of girls with polycystic ovary syndrome. It was concluded that patients with PCOS had a lower quality of life score. The variables of age, menstrual disorders, and micromastia were determined as influencing factors the quality of life. The results of this study are significant and warrant further research in this area, particularly with regard to the financial resources of patients in the challenging economic circumstances facing the nation – the majority of which are brought on by economic sanctions. [ABSTRACT FROM AUTHOR]

There is increasing evidence that selenium (Se) and its major transport protein, selenoprotein-P (SePP), may be associated with polycystic ovary syndrome (PCOS). However, the association of serum Se and SePP levels with circulating adipokines in this population has not received sufficient attention. In the present study, we aimed to investigate the associations of serum Se and SePP with circulating adipokine levels in patients with PCOS. In this cross-sectional study, 115 patients aged 18–45 years with PCOS diagnosed according to the Rotterdam Consensus Criteria were recruited. The general characteristics of the participants were collected using a general questionnaire and anthropometric measurements were taken. Blood samples were obtained and serum levels of leptin, adiponectin, visfatin, resistin, and omentin-1, as well as markers of glucose metabolism, were measured. Serum levels of Se and SePP were inversely correlated with fasting blood glucose (FBS), serum insulin, and homeostatic model assessment for insulin resistance (HOMA-IR). In addition, serum levels of Se and SePP were positively correlated with serum levels of adiponectin and visfatin. Although there was no significant correlation between serum Se and serum omentin-1 levels, a significant positive correlation was found between serum SePP levels and this adipokine. The present study found that serum Se and SePP levels were positively correlated with serum adiponectin and visfatin levels. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Copyright of Anatolian Journal of General Medical Research is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction and purpose: Polycystic ovary syndrome (PCOS) is the most common endocrine disease in the female reproductive age. As treatment guidelines include lifestyle changes, various diet types are being evaluated in terms of efficacy among them ketogenic diet (KD) which was also assessed in terms of its influence on another ovarian related disease - ovarian cancer. The aim of this paper is an analysis of the available scientific data in respect of the role of the KD as a part of the therapy of ovarian related disorders. The search was conducted using PubMed and Google Scholarship databases. Brief description of the state of knowledge: Ketogenic diet demonstrates favorable effects in the hormonal profile of PCOS-affected women. It was also noticed that its administration results in the reduction of BMI and the improvement in glycemic parameters. Most of the research was conducted by linking the ketogenic diet with the caloric restriction. In the matter of ovarian cancer the results are unclear; some of the research states the improvement of the quality of life of the participants, but there is some alarming data of the possible role of KD in enhancing the tumor growth. Conclusions: Ketogenic diet merits further research as a possible factor in the treatment of PCOS as foregoing results are pointing to its efficacy. Nevertheless, still more data is needed to determine its role as studies were conducted within a short period of time with relatively small research groups. There are also other limitations such as the lack of comparison with other dietary patterns with the caloric deficit which makes it difficult to deduce the main profitable factor. When it comes to ovarian cancer the results of the current data are also unclear and unambiguous with the possible negative effects. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFASs) are a class of anthropogenic organic compounds widely present in the natural and human living environments. These emerging persistent pollutants can enter the human body through multiple channels, posing risks to human health. In particular, exposure to PFASs in women may cause a series of reproductive health hazards and infertility. Based on a review of the existing literature, this study preliminarily summarizes the effects of PFAS exposure on the occurrence and development of female reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS), endometriosis, primary ovarian insufficiency (POI), and diminished ovarian reserve (DOR). Furthermore, we outline the relevant mechanisms through which PFASs interfere with the physiological function of the female ovary and finally highlight the role played by nutrients in reducing the reproductive health hazards caused by PFASs. It is worth noting that the physiological mechanisms of PFASs in the above diseases are still unclear. Therefore, it is necessary to further study the molecular mechanisms of PFASs in female reproductive diseases and the role of nutrients in this process. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this systematic review was to evaluate the effects of testosterone on uterine and ovarian pathology in transmasculine patients at the time of gender-affirming surgery. Methods: Searches were conducted using MEDLINE, CINAHL with Full Text, Cochrane Library, Scopus, and Europe PMC for articles published before April 5, 2021, containing concepts of testosterone use, uterine histopathology, and transgender population. The initial search yielded a total of 658 abstracts. Studies were analyzed in full text if they reported one or more uterine or ovarian histopathological findings in a noncisgender population receiving testosterone for gender affirmation. Rayyan software was used for the abstract review. Results: This review was registered with PROSPERO. Twenty-eight full-text articles were reviewed, of which 17 met the inclusion criteria. Two reviewers performed data extraction and risk of bias assessment. Thirteen studies included endometrial histopathology results, representing 522 patients. Endometrial findings demonstrated that 254 patients (48.7%) were atrophic, 243 (46.6%) were proliferative, and 16 (3.0%) were secretory. Twelve patients (2.3%) had endometrial intraepithelial neoplasia (EIN), including one (0.2%) with focal adenocarcinoma. Eleven studies reported ovarian histopathology in 410 patients and 765 ovaries. A total of 143 (34.9%) patients had polycystic-appearing ovaries. Three (0.7%) patients had benign ovarian neoplasms. No ovarian malignancies were reported. Conclusion: The endometrium was predominately found to be atrophic or proliferative, with low rates of EIN and carcinoma. No ovarian malignancy was observed. Based on this review, patients on testosterone do not have an increased risk of precancerous endometrial lesions due to unopposed hormones in the setting of amenorrhea. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the differential variations in the metabolic composition of follicular fluid (FF) among normal-weight patients with polycystic ovary syndrome (PCOS) and controls and to identify potential biomarkers that may offer insights into the early identification and management of these patients. Methods: We collected FF samples from 45 normal-weight women with PCOS and 36 normal-weight controls without PCOS who were undergoing in vitro fertilization–embryo transfer. An untargeted metabolomic study of collected FF from infertile women was performed using high-performance liquid chromatography–tandem spectrometry (LC-MS). The tendency of the two groups to separate was demonstrated through multivariate analysis. Univariate analysis and variable importance in projection were used to screen out differential metabolites. Metabolic pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a diagnostic model was established using the random forest algorithm. Results: The metabolomics analysis revealed an increase in the expression of 23 metabolites and a decrease in that of 10 metabolites in the FF of normal-weight women with PCOS. According to the KEGG pathway analysis, these differential metabolites primarily participated in the metabolism of glycerophospholipids and the biosynthesis of steroid hormones. Based on the biomarker combination of the top 10 metabolites, the area under the curve value was 0.805. The concentrations of prostaglandin E2 in the FF of individuals with PCOS exhibited an inverse association with the proportion of high-quality embryos (p < 0.05). Conclusions: Our research identified a distinct metabolic profile of the FF from normal-weight women with PCOS. The results offer a broader comprehension of the pathogenesis and advancement of PCOS, and the detected differential metabolites could be potential biomarkers and targets for the treatment of PCOS. [ABSTRACT FROM AUTHOR]

The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The US Food and Drug Administration has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering promise for guiding the advancement of PCOS treatments. In this context, we outline the genetic and epigenetic advancement in PCOS, which provide novel insights into the pathogenesis of this complex disease. We also delve into the prospective method for harnessing genetic and epigenetic strategies to identify potential drug targets and ensure target safety. Additionally, we shed light on the preliminary evidence and distinctive challenges associated with gene and epigenetic therapies in the context of PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a diverse endocrine disorder widely recognized as the prevailing metabolic condition among women in their reproductive years. The precise pathophysiological mechanisms underlying PCOS remain incompletely understood. However, existing evidence suggests that the development of PCOS may be linked to factors such as abdominal obesity, hyperandrogenism, and insulin resistance (IR). Excessive central adiposity in women with PCOS may lead to the development of a chronic, low-grade inflammation characterized by the activation of proinflammatory cytokines. The cytokines that belong to the IL-12 family are a collection of distinct heterodimeric cytokines that include IL-12, IL-23, IL-27, and IL-35. Recent research has provided further evidence regarding the significance of IL-12 cytokines in influencing both innate and adaptive immune responses in different diseases. Additionally, these studies have discovered diverse roles for certain members of the IL-12 family, encompassing multiple immunological functions that can either act as effectors or regulators. In this discourse, we examine the distinctive and atypical structural and functional attributes of this particular cytokine family. This study aims to offer a comprehensive overview of the pathophysiological significance of the IL-12 family cytokines in PCOS patients. Additionally, the therapeutic potential of the cytokines as novel approaches for PCOS treatment will be proposed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polycystic ovary syndrome (PCOS) is a complex disorder that can negatively impact the obstetrical outcomes. The aim of this study was to determine the predictive performance of four machine learning (ML)-based algorithms for the prediction of adverse pregnancy outcomes in pregnant patients diagnosed with PCOS. Materials and Methods: A total of 174 patients equally divided into 2 groups depending on the PCOS diagnosis were included in this prospective study. We used the Mantel–Haenszel test to evaluate the risk of adverse pregnancy outcomes for the PCOS patients and reported the results as a crude and adjusted odds ratio (OR) with a 95% confidence interval (CI). A generalized linear model was used to identify the predictors of adverse pregnancy outcomes in PCOS patients, quantifying their impact as risk ratios (RR) with 95% CIs. Significant predictors were included in four machine learning-based algorithms and a sensitivity analysis was employed to quantify their performance. Results: Our crude estimates suggested that PCOS patients had a higher risk of developing gestational diabetes and had a higher chance of giving birth prematurely or through cesarean section in comparison to patients without PCOS. When adjusting for confounders, only the odds of delivery via cesarean section remained significantly higher for PCOS patients. Obesity was outlined as a significant predictor for gestational diabetes and fetal macrosomia, while a personal history of diabetes demonstrated a significant impact on the occurrence of all evaluated outcomes. Random forest (RF) performed the best when used to predict the occurrence of gestational diabetes (area under the curve, AUC value: 0.782), fetal macrosomia (AUC value: 0.897), and preterm birth (AUC value: 0.901) in PCOS patients. Conclusions: Complex ML algorithms could be used to predict adverse obstetrical outcomes in PCOS patients, but larger datasets should be analyzed for their validation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization. [ABSTRACT FROM AUTHOR]