Effects of different PCOS phenotypes on placental three-dimensional power Doppler indices and placental volume during the first trimester.

INTRODUCTION: The aim of the present study was to evaluate the effects of different polycystic ovary syndrome (PCOS) phenotypes using first-trimester placental three-dimensional power Doppler indices and placental volume. METHODS: In this prospective case-control study, 170 pregnant women who met the inclusion criteria were divided into five groups according to PCOS phenotype: non-PCOS control (n = 34), PCOS phenotype A (n = 34), PCOS phenotype B (n = 34), PCOS phenotype C (n = 34), and PCOS phenotype D (n = 34). The primary outcomes determined in the present study were the differences in placental volume and placental flow index (FI), vascularization flow index (VFI), vascularization index (VI), and uterine artery pulsatility index (PI) betweenthe PCOS groups and control group. RESULTS: The mean placental volume and VI were significantly decreased in the phenotype A, B, and C groups compared to the control group and PCOS phenotype D group. The mean FI and VFI were significantly decreased in the phenotype A and B groups compared to the control group and PCOS phenotype C and D groups. The mean testosterone, dehydroepiandrostenedione, sex-hormone binding globulin, free androgen index, and insulin resistance levels were significantly increased in the phenotype A, B, and C groups compared to the control group and PCOS phenotype D group. DISCUSION: The results indicated that placental volume and placental vascular Doppler indices in the first trimester were more adversely affected in the PCOS A and B phenotypes than other PCOS phenotypes.

Common Beverage Consumption and Benign Gynecological Conditions.

The purpose of this article is to review the effects of four commonly consumed beverage types-sugar-sweetened beverages (SSBs), caffeinated beverages, green tea, and alcohol-on five common benign gynecological conditions: uterine fibroids, endometriosis, polycystic ovary syndrome (PCOS), anovulatory infertility, and primary dysmenorrhea (PD). Here we outline a plethora of research, highlighting studies that demonstrate possible associations between beverage intake and increased risk of certain gynecological conditions-such as SSBs and dysmenorrhea-as well as studies that demonstrate a possible protective effect of beverage against risk of gynecological condition-such as green tea and uterine fibroids. This review aims to help inform the diet choices of those with the aforementioned conditions and give those with uteruses autonomy over their lifestyle decisions.

Prevalence and correlates of diagnosed and probable polycystic ovary syndrome (PCOS) in a cohort of parous women.

OBJECTIVES: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women. METHODS: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups. RESULTS: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin. CONCLUSIONS: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity.

Exercise in the management of polycystic ovary syndrome: A position statement from Exercise and Sport Science Australia.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition amongst females of reproductive age, leading to lifelong cardiometabolic, reproductive, psychological, and dermatologic symptoms as well as a reduced quality of life. Lifestyle interventions, which can include structured exercise programmes delivered by appropriately trained exercise professionals such as clinical exercise physiologists, are considered first-line strategies in PCOS management due to their therapeutic effects on various health outcomes and quality of life. This position statement builds on the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS and describes the role of the exercise professional in the context of the multidisciplinary care team which includes physicians and allied health professionals. This position statement aims to equip exercise professionals with a broad understanding of the pathophysiology of PCOS, how it is diagnosed and managed in clinical practice, and evidence- and consensus-based recommendations for physical activity and exercise in PCOS management. In line with the physical activity recommendations for the general public, individuals with PCOS should aim to undertake between 150 to 300min of moderate-intensity or 75 to 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week. Additionally, muscle-strengthening activities on two non-consecutive days per week are recommended to maintain health and prevent weight gain. For further health benefits and to achieve modest weight loss, individuals with PCOS should aim for a minimum of 250min of moderate-intensity or 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week, plus muscle-strengthening activities on two non-consecutive days per week. Adolescents with PCOS should aim for a minimum of 60min moderate- to vigorous-intensity activity each day, incorporating muscle- and bone-strengthening activities three times per week. Finally, exercise professionals should consider the significant psychological burden, including weight stigma, and the high prevalence of comorbidities amongst individuals with PCOS and take appropriate measures to deliver safe and efficacious exercise interventions.

Protective Effects of Changbudodam-tang on Cell Death Signals on the Bone Marrow-Derived Human Mesenchymal Stem Cells via Regulation of MKK7/JNK/c-Jun Signaling Pathway.

Objectives: Polycystic ovary syndrome (PCOS) is one of the most common disorders and it shows up to 20% prevalence in reproductive-aged women populations, but no cures are available to date. We aimed to investigate the protective effects of Changbudodam-tang (CBD) on cell death signaling pathways, inflammation, and oxidative stress observed in Bone-Marrow derived human mesenchymal stem cell (BM-hMSC) by means of PCOS therapeutics in the future. Methods: BM-hMSCs were applied with cell deaths and injuries. Apoptosis and pyroptosis signals were quenched with their related signaling pathways using quantitative PCR, Western blot, and fluorescence image analysis. Results: Our data clearly displayed hydrogen peroxide- and nigericin-treated cell death signaling pathways via regulations of mitochondrial integrity and interleukin (IL)-1ß at the cellular levels (p < 0.01 or 0.001). We further observed that pre-treatment with CBD showed protective effects against oxidative stress by enhancement of antioxidant components at the cellular level, with respect to both protein and mRNA expression levels (p < 0.05, 0.01 or 0.001). The mechanisms of CBD were examined by Western blot analysis, and it showed anti-cell death, anti-inflammatory, and antioxidant effects via normalizations of the Jun N-terminal kinase/mitogen-activated protein kinase kinase 7/c-Jun signaling pathways. Conclusion: This study confirmed the pharmacological properties of CBD by regulation of cellular oxidation and the inflammation-provoked cell death condition of BM-hMSCs, which is mediated by the MKK7/JNK/c-Jun signaling pathway.

The impact of obesity surgery on newborn anthropometrics in women with and without polycystic ovary syndrome.

PURPOSE: Obesity surgery and polycystic ovary syndrome (PCOS) are both associated with increased risk of intrauterine growth restriction. We investigated whether offspring of mothers with PCOS who underwent obesity surgery had an increased risk of deviating birth anthropometrics compared to offspring of mothers without PCOS. METHODS: In this observational study, data from two study databases (BAROBS and PregMet2) were supplemented with data from patient's records from secondary and tertiary hospitals. In total, 162 offspring born to mothers with PCOS (n = 48) and without PCOS (n = 114) were included. Forty-nine offspring were born prior to, and 113 after obesity surgery. RESULTS: Mean ± SD birthweight (BW), birth length (BL), and head circumference (HC) before and after surgery for offspring born to mothers with PCOS were 3987 ± 495 g vs 3396 ± 526 g (P = 0.001), 52.2 ± 1.6 cm vs 50.1 ± 2.2 cm (P = 0.010), and 36.3 ± 1.97 cm vs 35.3 ± 1.66 cm (P = 0.183), respectively. In the non-PCOS group BW, BL and HC before and after were 3859 ± 603 g vs 3490 ± 538 g (P = 0.001), 51.3 ± 2.0 cm vs 49.9 ± 2.5 cm (P = 0.013), and 36.4 ± 2.0 cm vs 35.3 ± 1.8 cm (P = 0.016), respectively. Post-surgery, we found no difference in z-score BW, (∆-0.08, P = 0.677), BL (∆0.21, P = 0.184), and HC (∆0.14, P = 0.476) between children of PCOS and non-PCOS mothers. COMCLUSION: Babies born after obesity surgery were smaller and shorter in both the PCOS and non-PCOS group. Post-surgery anthropometrics were similar in babies born to mothers with and without PCOS.

Cytoarchitectural differences in reproductive organs of some polycystic ovary-like induced animal models.

Polycystic ovary syndrome (PCOS) is the most common gynaecological, endocrine disorder that occurs during reproductive age and is a significant cause of anovulatory infertility. Letrozole is an aromatase inhibitor which negates the action of the aromatase enzyme, which results in the buildup of male hormones (testosterone) in the females, causing hyperandrogenism, which is a hallmark of Polycystic Ovarian Syndrome. Mifepristone (RU486) is a progestin antagonist that acts to arrest the actions of the progesterone hormone, resulting in follicular atresia and anovulation. DHEA is an androgen which was also administered in a bid to cause hyperandrogenism in the rats.This study aimed to evaluate the effects of these hormones on the cytoarchitecture of the ovaries and uterus to assess their various PCOS-like histological features.Animals were grouped mainly into three: Letrozole, Mifepristone and DHEA groups, which were further divided into two subgroups each, administered low and high doses of letrozole orally, Mifepristone and Dehydroepiandosterone (DHEA) subcutaneously. Each of the subgroups also had a comparison control group. Following the completion of administration, the Wistar rats were euthanized, and their ovaries and uterus were collected for histological analysis.Increased proliferation of ovarian follicles was noted in the treated groups compared to control, as well as thickening of the endometrial layer.

Association of diabetes mellitus with risk of reproductive impairment in females: A comprehensive review.

Reproductive impairment is the most prevalent yet most ignored complication of diabetes mellitus. In diabetes, the problem associated with reproductive health is comprehensive in both males and females. Diabetic females have problems like delayed menarche, irregular menstrual cycle, subfertility, complications in pregnancy and early menopause. This may decrease reproductive age in diabetic females as the menarche is delayed and menopause is early in them. Like diabetic males, diabetic females also have the negative effect of oxidative stress on the reproductive system. This may lead to dysfunction of the ovary. It affects the physiological cycle like the ovary's maturation, embryo development and pregnancy. These complications also affect the offspring, and they may also become diabetic. This review aims to concentrate on the effect of diabetes on the reproductive system of females and the impairment caused by it. We will also discuss in detail the role of the hypothalamus-pituitary ovary axis, diabetes impact on different reproductive phases of females, and the sexual disorders that occur in them.

Changes in adverse obstetrical and neonatal outcomes over time in American women with polycystic ovary syndrome: an 11-year study of a population database.

PURPOSE: To determine whether the prevalence in American demographic and resultant adverse obstetric outcomes changed in women with polycystic ovary syndrome between the years of 2004-2014 inclusively, based on data derived from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. METHODS: This is a retrospective population-based study using data derived from the HCUP-NIS database from the years of 2004-2014, inclusively. Within this group, all pregnancies to women with PCOS were identified and separated by year, creating 11 groups. RESULTS: Risk factors including non-Caucasian race, lower socioeconomic status, and rates of obesity and thyroid disease increased over time. The rates of gestational diabetes mellitus demonstrated a slight decrease, (21.3% in 2004 to 18.0% in 2014, P = 0.01). The number of women with preterm premature rupture of membranes decreased from 3.0% in 2004 to 2.0% in 2014 (P = 0.04). Rates of preterm delivery decreased from 14.8% in 2004 to 9.8% in 2014 (P < 0.001). Rates of cesarean section decreased from 57.3% in 2004 to 45.7% in 2014 (P < 0.001), while rates of spontaneous vaginal delivery increased from 37.4% in 2004 to 50.1% in 2014 (P < 0.001). The rate of wound complications decreased from 2.1% in 2004 to 0.4% in 2014 (P < 0.001). However, the rate of congenital anomalies increased from 0.5% in 2004 to 1.2% in 2014 (P = 0.001). CONCLUSIONS: In spite of increases in demographic risk factors associated with increased pregnancy complications, we hypothesize that the interventions made to minimize the risks of cesarean section and manage metabolic complications in women with PCOS during the period of study have resulted in improved pregnancy outcomes during the period of study.

Association of obstructive sleep apnea syndrome with polycystic ovary syndrome through bidirectional Mendelian randomization.

Background: Observational studies have established a link between polycystic ovary syndrome (PCOS) and obstructive sleep apnea syndrome (OSAS), with obesity being a significant confounding factor that complicates the understanding of causality. This study seeks to clarify the causal relationship by utilizing bidirectional two-sample Mendelian randomization (MR) analysis. Methods: A bidirectional MR strategy was implemented to investigate the potential causal relationship between PCOS and OSAS. Instrumental variables (IVs) for PCOS were sourced from a dataset comprising 3,609 cases and 229,788 controls. For OSAS, statistical data were obtained from a genome-wide association study (GWAS) involving 38,998 subjects, alongside a control group of 336,659 individuals. Our MR analysis utilized several methods, including inverse variance weighted (IVW), weighted mode, weighted median, simple mode, and MR-Egger, primarily focusing on the IVW technique. Sensitivity tests were conducted to ensure the robustness of our findings. Results: Utilizing the IVW method, we identified a notable causal association from OSAS to PCOS, with an odds ratio (OR) of 1.463 and a 95% confidence interval (CI) of 1.086-1.971 (p = 0.012). In the opposite direction, PCOS also appeared to significantly affect OSAS development, indicated by an OR of 1.041 and a 95% CI of 1.012-1.072 (p = 0.006). The MR-Egger intercept test showed no evidence of directional pleiotropy, affirming the credibility of our causal findings (p > 0.05). Conclusion: This study suggests a bidirectional causal relationship between PCOS and an increased risk of OSAS. These insights could guide future screening and prevention strategies for both conditions.

Nutritional and exercise interventions to improve conception in women suffering from obesity and distinct nosological entities.

Infertility among women, particularly those living with obesity, presents a multifaceted challenge with implications for reproductive health worldwide. Lifestyle interventions, mainly focusing on weight loss, have emerged as promising strategies to improve fertility outcomes in this population. This review aims to explore the effectiveness of various lifestyle interventions, encompassing dietary modifications and exercise regimens, in enhancing fertility outcomes among women with obesity and associated conditions such as polycystic ovary syndrome, congenital adrenal hyperplasia, type 2 diabetes mellitus, premenopause, hypothyroidism and eating disorders. Methodology of study search encompass a broad spectrum, ranging from interventions targeting weight management through slow or rapid weight loss to dietary approaches emphasizing whole food groups, specific nutrients, and dietary patterns like low-carbohydrate or ketogenic diets, as well as the Mediterranean diet. By synthesizing existing findings and recommendations, this review contributes to the understanding of lifestyle interventions in addressing infertility, with an emphasis on the population of women of reproductive age with excess weight and known or unknown infertility issues, while promoting their integration into clinical practice to optimize reproductive health and overall well-being.

Effect of melatonin supplementation on cardiometabolic risk factors, oxidative stress and hormonal profile in PCOS patients: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: To investigate whether melatonin supplementation can enhance cardiometabolic risk factors, reduce oxidative stress, and improve hormonal and pregnancy-related factors in patients with PCOS. METHODS: We conducted a systematic search of PubMed/Medline, Scopus, and the Cochrane Library for articles published in English from inception to March 2023. We included randomized controlled trials (RCTs) on the use of melatonin for patients with polycystic ovary syndrome (PCOS). We performed a meta-analysis using a random-effects model and calculated the standardized mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Six studies met the inclusion criteria. The result of meta-analysis indicated that melatonin intake significantly increase TAC levels (SMD: 0.87, 95% CI: 0.46, 1.28, I2 = 00.00%) and has no effect on FBS, insulin, HOMA-IR, TC, TG, HDL, LDL, MDA, hs-CRP, mFG, SHBG, total testosterone, and pregnancy rate in patients with PCOS compare to controls. The included trials did not report any adverse events. CONCLUSION: Melatonin is a potential antioxidant that may prevent damage from oxidative stress in patients with PCOS. However, the clear effect of melatonin supplementation on cardiometabolic risk factors, hormonal outcomes, and pregnancy-related outcomes needs to be evaluated further in large populations and long-term RCTs.

Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance.

INTRODUCTION: This study investigated changes in plasma microbial-derived extracellular vesicles (EVs) in patients with polycystic ovary syndrome and insulin resistance (PCOS-IR) before and after metformin treatment, and aimed to identify bacterial taxa within EVs that were biologically and statistically significant for diagnosis and treatment. METHODS: The case-control study was conducted at Xiamen Chang Gung Hospital, Hua Qiao University. Plasma samples were collected from five PCOS-IR patients of childbearing age before and after 3 months of metformin treatment, and the samples were sequenced. The diversity and taxonomic composition of different microbial communities were analyzed through full-length 16 S glycosomal RNA gene sequencing. RESULTS: After metformin treatment, fasting plasma glucose levels and IR degree of PCOS-IR patients were significantly improved. The 16 S analysis of plasma EVs from metformin-treated patients showed higher microbial diversity. There were significant differences in EVs derived from some environmental bacteria before and after metformin treatment. Notably, Streptococcus salivarius was more abundant in the metformin-treated group, suggesting it may be a potential probiotic. DISCUSSION: The study demonstrated changes in the microbial composition of plasma EVs before and after metformin treatment. The findings may offer new insights into the pathogenesis of PCOS-IR and provide new avenues for research.

The latest reports and treatment methods on polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an increasingly recognized endocrine disorder. The pathogenesis is not fully known. Polycystic ovary syndrome is still difficult to diagnose correctly, despite simple diagnostic criteria. The aim of the study is to review the current knowledge about PCOS and treatment options for patients with the disease. To explore this topic, publications were reviewed and conclusions drawn from them. The incidence of hyperandrogenism in a patient with PCOS may be as high as 60-80%. Increased androgen levels affect ovulation and menstruation, and also result in hirsutism and acne. Additionally, patients have problems with proper glucose tolerance (insulin resistance), type 2 diabetes, hypertension, cardiovascular diseases and metabolic syndrome. PCOS results in various symptoms in patients.The latest treatment methods were analysed. A standard review of publications in the field of diagnosis and treatment of PCOS, IR and hyperandrogenism was used.Lifestyle, especially diet, deserves special attention due to its ease of use. Sleep quality, physical activity and stress reduction are also important. Diet should be the treatment of first choice. Only if dietary intervention does not bring results, the doctor considers pharmacotherapy. Recently, acupuncture and herbal medicine, vagus nerve stimulation have been used in the treatment of PCOS and regulation of hormone levels. Patients are given supplementation to improve the quality of functioning, but it must be remembered that inappropriate doses or too long use may result in a toxic effect opposite to the therapeutic one.Appropriate diet, physical activity - lifestyle changes are crucial in the treatment of PCOS. Supplementation and pharmaceuticals support treatment. It is mandatory to examine these environmental and lifestyle factors as they not only contribute to the occurrence of the disease but also influence its progression.

Polycystic ovary syndrome (PCOS) is a complex metabolic and hormonal disorder that occurs in women. It manifests itself in menstrual disorders, changes in appearance related to excessive hair growth and acne. PCOS is also associated with the risk of other diseases, glucose tolerance (insulin resistance), type 2 diabetes, hypertension, cardiovascular diseases and metabolic syndrome. Polycystic ovary syndrome is still difficult to diagnose correctly, despite simple diagnostic criteria.The symptoms and course of the disease vary, specific to each patient. Patients struggle with PCOS, not being aware that it is a significant medical problem. The patients have always had problems with menstruation, so they think it is normal.The article reviews and describes various treatment methods: Hormone therapy, pharmacological methods, supplementation, non-pharmacological methods such as herbal medicine, acupuncture.

Productivity loss due to polycystic ovary syndrome and its relationship to race, mental health and healthcare delivery indices.

Objective: To study the impact of polycystic ovary syndrome (PCOS) on work-related impairments and explore relationships with race, mental health, and healthcare delivery indices. Design: A cross-sectional internet-based survey. Setting: North American women with PCOS between August 2022 and October 2022. Patients: Individuals with a self-reported diagnosis of PCOS. Interventions: Not applicable. Main Outcome Measures: The primary outcome was missed work because of PCOS. The secondary outcomes included leave from work, impacts on the quality of work, and feelings of being held back at work because of PCOS. Results: Of 1,105 respondents, 1,058 reported having PCOS diagnosed by a physician. Of this group, 50.4% reported missing work because of PCOS, 72% felt that PCOS impacted the quality of their work, and 51.5% felt held back at work by PCOS. Multivariate analyses revealed that missing work because of PCOS was independently associated with black race, lack of insurance, requiring multiple doctors for a PCOS diagnosis, needing ≥3 doctors for current care, decreased satisfaction with care, and symptoms of anxiety and depression. Conclusions: Polycystic ovary syndrome significantly impacts employment-related productivity. Factors such as race, mental health, and healthcare delivery appear to play a crucial role in the extent of this impact.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Targeted inhibition of kisspeptin neurons reverses hyperandrogenemia and abnormal hyperactive LH secretion in a preclinical mouse model of polycystic ovary syndrome.

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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). PARTICIPANTS/MATERIALS, SETTING, 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): 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.

Association of Polycystic Ovarian Syndrome (PCOS) With Vaginal Microbiome Dysbiosis: A Scoping Review.

The aim of this scoping review was to explore the potential relationship between vaginal microbiome dysbiosis and polycystic ovarian syndrome (PCOS). Four databases were utilized to identify primary literature based on a pre-determined exclusion and inclusion criteria. The electronic databases searched include MEDLINE, Embase, Cochrane Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. After an initial double-blind screening and removal of duplicates, 81 articles remained. Articles were included based on preselected inclusion and exclusion criteria, type of study, and date of publishing. Specifically, primary literature that focused on subjects that were diagnosed with PCOS and that discussed PCOS in relation to the vaginal microbiome was included. Literature reviews, studies with animal subjects, and studies that did not discuss PCOS and the vaginal microbiome were excluded. Current data from the five articles included in this review suggests that there is a relationship between PCOS and vaginal microbiome dysbiosis. Specifically, dysbiosis of the vaginal flora may be due to vaginal pH alterations secondary to decreased vaginal Lactobacillus species and elevated pathogenic species including Streptococcus, Actinomyces, Prevotella, Gardnerella, and Mycoplasma species. The manifestation of this vaginal microbiome dysbiosis is often bacterial and fungal vaginitis. Therefore, more studies are needed to explore the possibility of treating PCOS with probiotics designed to reestablish a healthy Lactobacillus-dominant vaginal microbiome. In addition, further studies on the microbial composition of the vaginal microbiota in PCOS patients could identify microbial biomarkers for diagnosing PCOS.