Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis of PCOS involves a complex interplay of genetic and environmental factors, including insulin resistance (IR) and resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, and adipose tissue, activate downstream signaling pathways like PI3K-AKT and MAPK-ERK upon binding. These pathways regulate glucose uptake, storage, and lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis and insulin signaling. Environmental factors such as endocrine-disrupting chemicals and lifestyle choices also exacerbate PCOS traits. Other than lifestyle modification and surgical intervention, management strategies for PCOS can be achieved by using pharmacological treatments like antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, and ovulation drugs to improve insulin sensitivity and ovulatory function, as well as combined oral contraceptives with or without cyproterone to resume menstrual regularity. Despite the complex pathophysiology and significant economic burden of PCOS, a comprehensive understanding of its molecular and cellular mechanisms is crucial for developing effective public health policies and treatment strategies. Nevertheless, many unknown aspects of PCOS, including detailed mechanisms of actions, along with the safety and effectiveness for the treatment, warrant further investigation.

Background: Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. Methods: A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, androstenedione), SHBG, and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration\'s tool for RCTs and the Newcastle-Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and the 95% confidence interval (95%CI) of circulating inflammatory markers, androgens, and LH between baseline and post-weight loss values. Results: Eleven studies (n = 323) were eligible for the systematic review, of which nine (n = 286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n = 286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n = 140), TNF-α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n = 162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n = 147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n = 197) after weight loss compared to baseline levels among PCOS women. A meta-analysis of five studies (n = 173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD -0.43, 95%Cl, -0.65, -0.21). Conclusions: These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation.
METHODS: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.
RESULTS: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well.
CONCLUSIONS: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS.

UNASSIGNED: Polycystic ovary syndrome (PCOS) is an endocrine metabolic disorder in reproductive-aged women. The study was designed to investigate the metabolic characteristics of different phenotypes in women with PCOS of reproductive age.
UNASSIGNED: A total of 442 women with PCOS were recruited in this cross-sectional study. According to different phenotypes, all women were divided into three groups: the chronic ovulatory dysfunction and hyperandrogenism group (OD-HA group, n = 138), the chronic ovulatory dysfunction and polycystic ovarian morphology group (OD-PCOM group, n = 161), and the hyperandrogenism and polycystic ovarian morphology group (HA-PCOM group, n = 143). The metabolic risk factors and prevalence rates of metabolic disorders among the three groups were compared.
UNASSIGNED: The body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) of women from the OD-HA group and HA-PCOM group were significantly higher than those of women from the OD-PCOM group (p < 0.05). The serum insulin concentration and homeostasis model assessment of insulin resistance (HOMA IR) at 2 h and 3 h after oral glucose powder in women from the OD-HA group and HA-PCOM group were significantly higher than those from the OD-PCOM group (p < 0.05). The serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in women from the OD-HA group and HA-PCOM group were significantly higher than those in women from the OD-PCOM group (p < 0.05). The prevalence rates of impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), insulin resistance (IR), metabolic syndrome (MS), nonalcoholic fatty liver disease (NAFLD), and dyslipidemia of women with PCOS were 17.9%, 3.6%, 58.4%, 29.4%, 46.6%, and 43.4%, respectively. The prevalence rates of IGT, IR, MS, NAFLD, and dyslipidemia of women in the OD-HA group and HA-PCOM group were significantly higher than those of women in the OD-PCOM group (p < 0.05). T concentration (>1.67 nmol/L) and Ferriman-Gallwey (F-G) score (>3) significantly increased the risk of metabolic disorders in women with PCOS (p < 0.05).
UNASSIGNED: The phenotypes of OD-HA and HA-PCOM in women with PCOS were vulnerable to metabolic disorders compared to OD-PCOM. Thus, the metabolic disorders in women with PCOS especially those with the HA phenotype should be paid more attention in order to reduce long-term complications.

Idiopathic hirsutism (IH) is a common clinical condition with multiple diagnostic and therapeutic uncertainties. There are no clear recommendations for the diagnosis and management of the condition. This practice update was developed to guide the primary care physicians and the specialists in better and more systematic management of IH particularly in the Indian context. Twelve experienced members consisting of eminent endocrinologists, physicians, a dermatologist, a gynaecologist and a psychiatrist were invited by the Integrated Diabetes and Endocrine Academy (IDEA). A literature search was performed using online databases from PubMed, Cochrane Library and Google Scholar. Published articles from peer-reviewed indexed journals, with a preference for meta-analyses and randomized controlled trials, were selected. A meeting took place with all the 12 members individually giving their opinions on predetermined questions of interest. After the initial meeting during IDEACON 2023, two more meetings were held and the practice update was formulated after voting. Practice updates were made on important areas such as the cut-off for modified Ferriman-Gallwey Score for the Indian population, conditions to be excluded before diagnosing IH, when to refer to specialists, investigations in a suspected case of IH and choice of therapies for its management.

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.

Polycystic ovary syndrome (PCOS) is a leading cause of infertility, with an estimated worldwide prevalence between 5% and 15%. We conducted a case-control study with 121 PCOS patients and 155 controls to assess the association between coffee intake and the presence of having a diagnosis of PCOS in women in Murcia, Spain. The PCOS diagnosis was determined following Rotterdam criteria (the presence of two of the following three conditions: hyperandrogenism, oligo-anovulation, and/or polycystic ovarian morphology). Coffee consumption was assessed using a validated food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. Coffee consumption was categorized into never, less than one cup per day, one cup per day, and two or more cups per day. We found a significant inverse linear trend: the higher the coffee consumption, the lower the probability of having PCOS in multivariable analysis (p-trend = 0.034). Women who presented with PCOS were less likely to drink one cup of coffee compared to those who had never drunk coffee (OR = 0.313, 95% CI: 0.141-0.69). The consumption of at least one cup of coffee per day may be associated with a decrease in PCOS symptoms.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with significant metabolic implications, including an increased risk of cardiovascular diseases and diabetes. Kallistatin, a serine proteinase inhibitor with anti-inflammatory and antioxidative properties, has been identified as a potential biomarker for PCOS due to its role in modulating inflammation and oxidative stress.
METHODS: This prospective cohort study was conducted at a university hospital\'s gynecology clinic. It included 220 women diagnosed with PCOS and 220 healthy controls matched for age and body mass index. Kallistatin levels were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA) techniques. Associations between kallistatin levels and clinical manifestations of PCOS, including hyperandrogenism and metabolic profiles, were examined.
RESULTS: Kallistatin levels were significantly lower in patients with PCOS (2.65 ± 1.84 ng/mL) compared to controls (6.12 ± 4.17 ng/mL; p < 0.001). A strong negative correlation existed between kallistatin levels and androgen concentrations (r = -0.782, p = 0.035). No significant associations were found between kallistatin levels and insulin resistance or lipid profiles.
CONCLUSIONS: The findings indicate that reduced kallistatin levels are closely associated with PCOS and could serve as a promising biomarker for its diagnosis. The specific correlation with hyperandrogenism suggests that kallistatin could be particularly effective for identifying PCOS subtypes characterized by elevated androgen levels. This study supports the potential of kallistatin in improving diagnostic protocols for PCOS, facilitating earlier and more accurate detection, which is crucial for effective management and treatment.

UNASSIGNED: To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation.
UNASSIGNED: Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included.
UNASSIGNED: The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%.
UNASSIGNED: Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant.
UNASSIGNED: Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.

OBJECTIVE: Do hyperactive kisspeptin neurons contribute to abnormally high LH secretion and downstream hyperandrogenemia in polycystic ovary syndrome (PCOS)-like conditions and can inhibition of kisspeptin neurons rescue such endocrine impairments?
CONCLUSIONS: Targeted inhibition of endogenous kisspeptin neuron activity in a mouse model of PCOS reduced the abnormally hyperactive LH pulse secretion and hyperandrogenemia to healthy control levels.
BACKGROUND: PCOS is a reproductive disorder characterized by hyperandrogenemia, anovulation, and/or polycystic ovaries, along with a hallmark feature of abnormal LH hyper-pulsatility, but the mechanisms underlying the endocrine impairments remain unclear. A chronic letrozole (LET; aromatase inhibitor) mouse model recapitulates PCOS phenotypes, including polycystic ovaries, anovulation, high testosterone, and hyperactive LH pulses. LET PCOS-like females also have increased hypothalamic kisspeptin neuronal activation which may drive their hyperactive LH secretion and hyperandrogenemia, but this has not been tested.
METHODS: Transgenic KissCRE+/hM4Di female mice or littermates Cre- controls were treated with placebo, or chronic LET (50 µg/day) to induce a PCOS-like phenotype, followed by acute (once) or chronic (2 weeks) clozapine-N-oxide (CNO) exposure to chemogenetically inhibit kisspeptin cells (n = 6 to 10 mice/group).
METHODS: Key endocrine measures, including in vivo LH pulse secretion patterns and circulating testosterone levels, were assessed before and after selective kisspeptin neuron inhibition and compared between PCOS groups and healthy controls. Alterations in body weights were measured and pituitary and ovarian gene expression was determined by qRT-PCR.
RESULTS: Acute targeted inhibition of kisspeptin neurons in PCOS mice successfully lowered the abnormally hyperactive LH pulse secretion (P < 0.05). Likewise, chronic selective suppression of kisspeptin neuron activity reversed the previously high LH and testosterone levels (P < 0.05) down to healthy control levels and rescued reproductive gene expression (P < 0. 05).
METHODS: N/A.
CONCLUSIONS: Ovarian morphology was not assessed in this study. Additionally, mouse models can offer mechanistic insights into neuroendocrine processes in PCOS-like conditions but may not perfectly mirror PCOS in women.
CONCLUSIONS: These data support the hypothesis that overactive kisspeptin neurons can drive neuroendocrine PCOS-like impairments, and this may occur in PCOS women. Our findings complement recent clinical investigations using NKB receptor antagonists to lower LH in PCOS women and suggest that pharmacological dose-dependent modulation of kisspeptin neuron activity may be a valuable future therapeutic target to clinically treat hyperandrogenism and lower elevated LH in PCOS women.
BACKGROUND: This research was supported by NIH grants R01 HD111650, R01 HD090161, R01 HD100580, P50 HD012303, R01 AG078185, and NIH R24 HD102061, and a pilot project award from the British Society for Neuroendocrinology. There are no competing interests.