Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and reproductive features, was emphasized. The proteomic analysis highlighted metabolic biology known to be related to PCOS. A polygenic risk score (PRS) was associated with adverse cardiometabolic outcomes, with differing relevance of testosterone and body mass index in women and men. Finally, while oligo-anovulation and anovulatory infertility are features of PCOS, we observed no impact of PCOS susceptibility on childlessness. We suggest that PCOS susceptibility confers balanced pleiotropic influences on fertility in women, and life-long adverse metabolic consequences in both sexes.

Polycystic Ovary Syndrome (PCOS) represents a complex endocrine-metabolic condition which presents with hyperandrogenism and anovulation together with insulin resistance and chronic low-grade inflammation affecting 21% of women during their reproductive years globally. Nutrition has always played a pivotal role in managing PCOS. Emerging evidence demonstrates that micronutrients play an essential part in regulating molecular processes that drive the pathophysiology of PCOS. The deficiency of micronutrients exacerbates insulin resistance, oxidative stress and hormonal dysregulation through their negative impact on PI3K/Akt, NF-κB and Nrf2 and steroidogenic enzyme signaling pathways, all of which play a key role in the pathophysiology of PCOS. This review synthesizes a comprehensive analysis of scientific findings which demonstrate how micronutrient levels influence the regulation of insulin function, inflammatory reactions, oxidative balance, methylation activities and ovarian health in PCOS patients. It also evaluates the potential advantages of targeted micronutrient supplementation used alongside standard management strategies, considering factors such as bioavailability and nutrigenomics, while emphasizing the need for robust large-scale randomized clinical trials. Overall, a molecularly targeted approach to micronutrients represents an emerging precision-nutrition strategy aimed at improving metabolic, reproductive, and inflammatory outcomes in women with PCOS.

Polycystic Ovary Syndrome (PCOS) is a leading cause of female infertility and is associated with various health complications, including preterm abortions, anovulation, and ovarian cancer. It affects approximately 5% to 10% of women in their reproductive years. PCOS diagnosis often relies on ultrasound imaging to assess ovarian follicle size, count and arrangement. Accurately diagnosing PCOS in clinical practice poses significant challenges for radiologists due to the variability in follicle sizes and their complex relationships with surrounding blood vessels and tissues. This process is labor-intensive, prone to errors, and time-consuming. To address these challenges, numerous research efforts have focused on automating the detection of PCOS-affected ovaries. While advancements have been made, further improvements are needed to enhance diagnostic accuracy. Convolutional Neural Networks (CNNs) have shown promise in PCOS classification, but models relying solely on global features may achieve suboptimal results, as regional features are often overlooked. This paper introduces a feature fusion model named PCOSFusionNet designed to improve the accuracy of PCOS classification. The proposed system combines handcrafted features extracted using the Histogram of Oriented Gradients (HOG) descriptor with global features obtained from the VGG19 deep learning model. Additionally, Contrast Limited Adaptive Histogram Equalization (CLAHE) is applied during preprocessing to enhance image quality and improve feature extraction. The watershed method is employed for segmentation before classification. By integrating deep features with handcrafted features, the system achieves superior classification performance across multiple metrics, including accuracy, precision, recall, and F1-score, using five-fold cross-validation. The performance of the proposed PCOSFusionNet model was evaluated on two publicly available datasets. The first dataset (Dataset_1) contains 3856 ultrasound images and the second dataset (Dataset_2) comprises 12,680 ultrasound images. On these datasets, PCOSFusionNet achieved accuracies of 98.49% and 98.30%, respectively, surpassing existing state-of-the-art methods and demonstrating its effectiveness in PCOS diagnosis.

Background and Objectives: Obesity is a major contributor to female reproductive dysfunction, frequently resulting in menstrual irregularity, anovulation, and subfertility. Bariatric surgery improves metabolic health; however, its effect on reproductive outcomes-particularly the shift from assisted to spontaneous conception-remains incompletely defined. This study aimed to evaluate the impact of laparoscopic sleeve gastrectomy (LSG) on menstrual cycle regularity and spontaneous pregnancy rates in women of reproductive age. Materials and Methods: This retrospective observational study included 52 women aged 18-40 years who underwent LSG between January 2013 and October 2017. Self-reported menstrual history, as documented during routine preoperative assessment in the electronic medical records, and reproductive outcomes (including spontaneous and assisted conception) were compared between the preoperative and postoperative periods. The median follow-up duration was 38 months. Results: A significant improvement in menstrual regularity was observed (46.2% to 94.2%, p < 0.001). Among women attempting conception, 10/15 (66.7%) achieved spontaneous pregnancy; one conceived via ART. Notably, 57.1% of all pregnancies occurred within the first 12 months post-surgery, including three unintended conceptions. Additionally, among women who conceived spontaneously, four had a history of requiring assisted reproductive technologies (ART), including two who had previously failed to conceive despite ART treatment. Conclusions: LSG is associated with significant normalization of menstrual cycles and a qualitative shift toward spontaneous conception in morbidly obese women. The rapid return of fertility, which may exceed patient awareness, underscores the importance of comprehensive perioperative counseling regarding effective contraception to prevent unintended pregnancies during the active weight-loss phase.

Acne vulgaris is one of the most prevalent dermatologic disorders in adolescent and adult women. Beyond classic pathogenic factors, such as sebaceous hypersecretion, follicular hyperkeratinization, Cutibacterium acnes overgrowth, and inflammation, endocrine drivers are pivotal. Polycystic ovary syndrome (PCOS) is common across reproductive ages and frequently presents with dermatologic manifestations, notably acne, through mechanisms dominated by hyperandrogenism and compounded by insulin resistance (IR). This narrative review synthesizes current evidence linking PCOS with acne, explains the interrelated roles of hyperandrogenism and IR, and outlines evidence-based management strategies tailored to women with PCOS. The Rotterdam diagnostic framework remains the globally favored standard for PCOS, emphasizing combinations of oligo-/anovulation, clinical/biochemical hyperandrogenism, and polycystic ovarian morphology. PCOS pathophysiology involves dysregulation of the hypothalamic-pituitary-ovarian axis with increased gonadotropin-releasing hormone pulsatility, elevated luteinizing hormone, and suppression of follicle-stimulating hormone, promoting thecal androgen excess and impaired folliculogenesis. IR, prevalent in PCOS, augments ovarian/adrenal androgen synthesis and lowers sex hormone-binding globulin levels, increasing free testosterone and sebum production; IGF-1 signaling further amplifies sebogenesis and follicular hyperkeratinization. Emerging data implicate genetic/epigenetic determinants, endocrine-disrupting chemicals, gut microbiome dysbiosis, and endoplasmic reticulum stress as modulators of the PCOS-acne phenotype. Epidemiologic studies and meta-analyses report higher acne prevalence and severity in PCOS, particularly among adolescents. First-line therapy includes combined oral contraceptive pills with antiandrogenic progestins; spironolactone is an effective adjunct. Where indicated, metformin addresses IR and may improve acne and ovulatory function. Judicious use of standard acne modalities such as topical retinoids, benzoyl peroxide, and oral/topical antibiotics remains essential; oral isotretinoin is reserved for refractory disease with careful risk management. PCOS-associated acne reflects converging endocrine and metabolic disturbances. Integrating androgen-targeted therapy, IR mitigation, and guideline-based acne care provides the most durable control. Future research should refine phenotype-directed treatment and clarify the contributions of microbiome, environmental exposures, and cellular stress pathways.

Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder affecting 5%-18% of women of reproductive age worldwide. It is characterized by hyperandrogenemia (HA), anovulation, and polycystic ovarian morphology (PCOM), severely impacting women's reproductive and metabolic health. Obesity has become increasingly common among PCOS patients in recent years. Obesity can further exacerbate the metabolic and reproductive dysfunctions of PCOS through mechanisms such as insulin resistance (IR) and chronic low-grade inflammation. It may even have adverse effects on mental health. However, the specific pathogenesis and effective therapeutic targets of PCOS with obesity remain incompletely understood. This review presents a narrative review of recent research, focusing on the molecular mechanisms that drive autophagy in the context of obesity associated with polycystic ovary syndrome (PCOS), endoplasmic reticulum stress (ERS), gut microbiota imbalances, and disruptions in the hypothalamic-pituitary-ovarian (HPO) axis. It also explores corresponding therapeutic strategies. The aim is to provide fresh perspectives and insights for future mechanistic research and clinical interventions in this field.

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10-20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18-42), and the mean BMI was 30.6 kg/m[2] (17-51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = -0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = -0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = -0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = -0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = -0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that significantly affects both obese and non-obese women of reproductive age. Besides genetic and epigenetic factors, obesity and insulin resistance (IR) play a key role in the pathogenesis of PCOS, contributing to its endocrine, reproductive, and metabolic manifestations. Even though metformin remains a well-established treatment in the management of PCOS, emerging therapies and integrative approaches warrant comparison. This narrative review aims to understand the pathophysiology of PCOS and compare the role of metformin with that of new emerging therapies, including sodium-glucose cotransporter-2 (SGLT-2) inhibitors, oral contraceptive pills (OCPs), inositol supplements, and lifestyle modifications, thereby empowering clinicians to provide personalized medicine based on each patient's unique presentation. This review explores the safety, efficacy, and clinical outcomes of these interventions on weight reduction, hormonal balance, menstrual regularity, and metabolic outcomes in both obese and non-obese women with PCOS.