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From 1965-2015, immense strides were made into understanding the mechanisms underlying the common androgen excess disorders, premature adrenarche and polycystic ovary syndrome (PCOS). The author reviews the critical discoveries of this era from his perspective investigating these disorders, commencing with his early discoveries of the unique pattern of plasma androgens in premature adrenarche and the elevation of an index of the plasma free testosterone concentration in most hirsute women. The molecular genetic basis, though not the developmental biologic basis, for adrenarche is now known and 11-oxytestosterones shown to be major bioactive adrenal androgens. The evolution of the lines of research into the pathogenesis of PCOS is historically traced: research milestones are cited in the areas of neuroendocrinology; insulin resistance, hyperinsulinism, type 2 diabetes mellitus; folliculogenesis; androgen secretion; obesity; phenotyping, prenatal androgenization, epigenetics, and complex genetics. Large scale genome-wide association studies led to the 2014 discovery of an unsuspected steroidogenic regulator DENND1A (differentially expressed in normal and neoplastic development). The splice variant DENND1A.V2 is constitutively overexpressed in PCOS theca cells in long-term culture and accounts for their PCOS-like phenotype. The genetics are complex, however: DENND1A intronic variant copy number is related to phenotype severity, and recent data indicates that rare variants in a DENND1A regulatory network and other genes are related to PCOS. Obesity exacerbates PCOS manifestations via insulin resistance and pro-inflammatory cytokine excess; excess adipose tissue also forms testosterone. Polycystic ovaries in one-quarter of apparently normal women lie on the PCOS functional spectrum. Much remains to be learned.

Aim Methods Results Conclusions Describe the current phenotypes and clinical laboratory data regarding polycystic ovary syndrome (PCOS) in Japan, taking into account ethnic differences and obesity status.Data for 986 PCOS cases and 965 control cases were collected using a nationwide survey in Japan. Obese/overweight (body mass index [BMI] ≥25 kg/m2) and non‐obese/overweight (BMI <25 kg/m2) cases were compared.Japanese PCOS cases predominantly involved non‐obese/overweight patients, accounting for 75% of all cases. Among non‐obese/overweight PCOS cases, the incidence of both amenorrhea and clinical/biochemical hyperandrogenism was significantly lower than in obese/overweight PCOS cases, whereas the rate of elevated serum luteinizing hormone (LH) level was significantly higher. Even though the incidence of hirsutism in Japan is only 13.5%, the detection rate for hyperandrogenism increased by as much as 30.4% when hirsutism was added to the Japan Society of Obstetrics and Gynecology (JSOG) criteria for the diagnosis of hyperandrogenism in addition to elevated serum total testosterone level. When evaluated based on timing of blood sampling, the LH level and LH/follicle‐stimulating hormone ratio determined at the initial consultation involving a chief complaint of irregular menstrual cycle (after confirming the absence of follicles measuring ≥1 cm in diameter) were significantly higher than on days 2–3 or 4–6 of the menstrual cycle.Ethnic differences, including obesity status, affected the phenotype and clinical laboratory data of Japanese PCOS patients, such as the incidence rates of clinical/biochemical hyperandrogenism and the rate of elevated basal LH level. Adding hirsutism to the JSOG 2024 criteria would enhance the accuracy of PCOS diagnosis and enhance consistency with the Rotterdam 2003 criteria. Measuring basal LH level is useful for assessing the endocrinologic characteristics of Japanese PCOS cases, as well as lean Asian PCOS cases, but the timing of blood sampling can affect the result. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a disease affecting as many as about 10% of women of reproductive age, also 3-11% of teenage patients, and can lead to numerous complications and coexists with many diseases. Research is ongoing to establish an appropriate diagnostic and therapeutic path for adolescent girls with PCOS. It is also important to implement appropriate check-ups among teenagers with PCOS in order to prevent PCOS complications and initiate appropriate treatment as soon as possible and prevent the long-term consequences of these complications. The relationship between the cooccurrence of PCOS and diseases such as metabolic syndrome, hypertension, obesity, insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is increasingly being investigated. A great attention is also being paid to the problem of mental health in this group of patients. In our study, we will review the latest reports on the treatment of PCOS and look at the complications that this syndrome can cause. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complex and multifactorial endocrine disorder predominantly affecting premenopausal women, characterized by hyperandrogenism, chronic anovulation, and polycystic ovarian morphology. Hyperandrogenism, a central pathogenic factor, negatively influences metabolism through its effects on various tissues and organs, including adipose tissue, skeletal muscle, and the liver. The redistribution of adiposity towards visceral and intraperitoneal fat depots, driven by androgens, is correlated with an increased risk of abdominal obesity and insulin resistance. In skeletal muscles, hyperandrogenism induces a decrease in insulin sensitivity by disrupting insulin signaling and mitochondrial function, thereby contributing to the metabolic dysfunctions associated with PCOS. At the hepatic level, women with PCOS exhibit a higher prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), a relationship largely mediated by chronic inflammation and the proinflammatory effects of androgens. These findings underscore the importance of understanding the molecular mechanisms underlying the relationship between hyperandrogenism and metabolic dysfunctions in PCOS, with significant implications for the development of innovative and personalized therapeutic strategies. Given the high prevalence and significant impact of PCOS on metabolic health, future research should focus on elucidating these mechanisms and identifying more effective therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age. In Kazakhstan, the prevalence of this syndrome is particularly high compared with other countries and the global average. Currently, the diagnosis of PCOS is based on internationally established Rotterdam criteria, using hyperandrogenism as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible misdiagnosis, an additional criterion, especially for the diagnosis of PCOS in obese women, could be considered. The aim of this study was to identify whether anti-Müllerian hormone (AMH) or other biochemical criteria can be used for this purpose. Methods: A total of 138 women were recruited for this study and grouped into control (n = 46), obese subjects without PCOS (n = 67), and obese patients with PCOS (n = 25). The health status, anthropometric parameters, and serum indicators for glucose, glycosylated hemoglobin, and hormone levels were examined for all subjects. Statistical data were analyzed using GraphPad Prism 10 software for interpretation of the data. Results: Serum AMH, testosterone, and LH were positively correlated in obese PCOS patients, while AMH and FSH were negatively correlated. Compared with other biochemical indicators, the serum AMH and testosterone levels in obese PCOS patients were significantly higher than those in non-PCOS patients (regardless of obesity), and AMH was also positively correlated with testosterone. Conclusions: AMH appears to be a reliable criterion in addition to testosterone for the diagnosis of PCOS in obese women. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine syndromes affecting women at reproductive age. With increasing knowledge of the role of the microbiota in the pathogenesis of PCOS, new management strategies began to emerge. However, data on the impact of established treatment regimens, such as metformin and oral contraceptive agents, on the gut microbiota composition are scarce. This study aimed to evaluate the specificity of the gut microbiota in women with PCOS before and after treatment with oral contraceptives. Methods: We have systematically searched the following databases: PubMed/MEDLINE, Scopus, Web of Science and Google Scholar. The last search was performed on 13 May 2024. We included only full-text original research articles written in English. The risk of bias was assessed using a modified version of the Newcastle–Ottawa Scale. Results: The above described search strategy retrieved 46 articles. Additionally, 136 articles were identified and screened through Google Scholar. After removing duplicates, we screened the titles and abstracts, resulting in three eligible articles constituting the final pool. They were published between 2020 and 2022 and are based on three ethnically distinct study populations: Turkish, Spanish and American. The studies included a total of 37 women diagnosed with PCOS and using OCs. Conclusions: OC treatment does not seem to affect the gut microbiota in a significant way in patients with PCOS in short observation. Well-designed randomized controlled studies with adequate, unified sample size are lacking. [ABSTRACT FROM AUTHOR]

Background Polycystic ovary syndrome (PCOS) is a common female cardiometabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. Objective To determine the association between the prevalence of PCOS and obesity. Materials and methods A systematic review was conducted to identify population studies on PCOS prevalence globally through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institutes of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality. Results Fifty-eight studies with 85 956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria. Conclusion The prevalences of PCOS and obesity appear to be modestly associated, although our data cannot establish causality. This study also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology [ABSTRACT FROM AUTHOR]

Context Controversial results have emerged regarding whether polycystic ovary syndrome (PCOS) is protective or increases the risk of bone frailty. Objective This study investigated whether the PCOS condition affects bone parameters of premenopausal women. This is an update for a previous meta-analysis published in 2019. Data Sources We searched MEDLINE and Embase. Study Selection Studies were considered eligible for the update if published in English between October 1, 2018, and December 31, 2023. The diagnosis of PCOS should be based on National Institutes of Health criteria, the Rotterdam Consensus, Androgen Excess & PCOS Society criteria, or International Classification of Diseases codes in women over 18 years old. Only records with the Newcastle-Ottawa Scale ≥ 6 were selected for data extraction. Data Extraction Data were extracted by 2 independent reviewers. Data Synthesis We identified 31 studies that met the inclusion criteria for qualitative analysis from 3322 studies in the whole period (1990-2023). Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30 305 women with PCOS and 10,1907 controls. Contrasting profiles emerged after stratification using a body mass index (BMI) cutoff of 27 kg/m2. Individuals with PCOS and a BMI <27 kg/m2 exhibited lower vertebral and nonvertebral bone density, reduced bone turnover marker (osteocalcin), and increased bone resorption marker (C-terminal type I collagen) levels. Conversely, individuals with PCOS and a BMI ≥27 kg/m2 exhibited increased vertebral and nonvertebral bone mineral density, with no significant changes in bone formation and resorption markers (except osteocalcin). Conclusion The findings of this study alert for a low bone mass, low bone formation, and increased bone resorption PCOS with a BMI <27 kg/m2. [ABSTRACT FROM AUTHOR]

This meeting report discusses the progress in inositol research within the field of polycystic ovary syndrome (PCOS). It highlights the role of inositol as an insulin sensitizer and its involvement in steroidogenesis. The report explores the efficacy of myo-inositol in treating PCOS, including its ability to improve hormonal, reproductive, and metabolic alterations commonly seen in hyperandrogenic PCOS. The authors suggest that the combination of myo-inositol and α-lactalbumin has a synergistic effect that is more effective than myo-inositol alone in treating PCOS. They also propose that PCOS should be stratified into different clinical subtypes for personalized treatment approaches. The study emphasizes the importance of considering factors such as inositol ratios, absorbance rates, and insulin resistance when using inositol therapy for PCOS. [Extracted from the article]

Objective: One of the main features of polycystic ovary syndrome (PCOS) is increased adipose tissue, which can result in hormonal disturbances. In the present study, we aimed to investigate which indicator of obesity could better associate with hormonal disturbances in PCOS women. Methods: In this cross-sectional analysis, women with PCOS were included according to the Rotterdam criteria. Fasting blood samples were analyzed for biochemical, metabolic, and hormonal parameters. Anthropometric measures comprised body composition indices (assessed by bioelectric impedance analysis [BIA]), waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR). Linear regression modeling was used to assess the association between anthropometric indices and hormonal imbalance, adjusted for age, mensuration status, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR). Receiver operating characteristics (ROC) curves were utilized to ascertain the sensitivity, specificity, and optimal cut-off points of various anthropometric indices in identifying hyperandrogenism. Results: A total of 129 PCOS women with a median (interquartile range [IQR]) age of 32.0 (23.0–32.0) years and a median BMI of 26.3 (23.00-29.70) kg/m2 were enrolled. In the adjusted linear regression model, BMI (β = 0.053, P < 0.001), waist circumference (β = 0.021, P = 0.001), WHtR (β = 3.325, P = 0.002), total fat mass (β = 0.021, P = 0.002), trunk fat mass (β = 0.038, P = 0.006), and leg fat mass (β = 0.045, P = 0.004) were positively associated with free androgen index (FAI). In addition, BMI (β=−0.017, P = 0.003), waist circumference (β=−0.008, P = 0.002), WHtR (β=−1.167, P = 0.004), total fat mass (β=−0.008, P=0.003), trunk fat mass (β=−0.017, P=0.001), and leg fat mass (β=−0.018, P=0.004) were negatively associated with the serum level of sex hormone binding globulin (SHBG). WHtR showed the greatest area under the curve (AUC) value (AUC = 0.676, P = 0.001) for identifying hyperandrogenism (FAI ≥ 4.97 or total testosterone ≥ 0.7 ng/mL) in PCOS women with corresponding sensitivity of 87.30% and specificity of 39.70%. Conclusions: WHtR is related to hyperandrogenism in PCOS better than other anthropometric measures. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting one in five women of reproductive age. Polycystic appearance of the ovaries in ultrasonography is associated with oligomenorrhea, and clinical and or biochemical hyperandrogenism. PCOS has been associated with voice alterations for many years. However, there is insufficient research on voice analysis in PCOS patients. Objectives: This research aimed to examine the voice characteristics among women with PCOS. Patients and methods: Our study included 25 women confirmed with PCOS and 25 control. A complete voice assessment was performed for all participants using primary demographic data, vocal symptoms, auditory perceptual evaluation of the voice, Arabic version of the Voice Handicap Index, acoustic analysis, and video laryngoscopic examination of the larynx. Results: Our study revealed statistically significant differences between PCOS and control groups in phonasthenic symptoms, auditory perceptual assessment of the voice, acoustic parameters, and laryngoscopic examination. Conclusion: PCOS women with hirsutism are complaining of vocal symptoms, changes in vocal characters, and deterioration of the acoustic parameters of the voice. High serum levels of androgen can cause the deepening of the voice, which is essential for the early detection of vocal symptoms in PCOS patients to prevent virilization of their voice. Trial registration: NCT06085170. Registered 20 August 2023—retrospectively registered, https://www.google.com/url?sa=t&source=web&rct=j&opi=89978449&url=https://classic.clinicaltrials.gov/ct2/show/NCT06085170&ved=2ahUKEwjEyLqUq6KGAxWxRPEDHb57DIQQFnoECBQQAQ&usg=AOvVaw1xTurnA6mJEZ9PK0vQS8VL. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the intima-media thickness (IMT) and elasticity of the carotid artery in non-obese polycystic ovary syndrome (PCOS) patients using a quantitative technique for vascular elasticity measurement and to explore the influencing factors. Methods: Sixty non-obese patients without metabolic and cardiovascular diseases who were diagnosed with PCOS in the Women and Children's Hospital of Chongqing Medical University from January to December 2022 were prospectively selected (case group), and 60 healthy volunteers matched for body mass index were included as the control group. Body weight, height, heart rate, blood pressure, and waist-to-hip ratio were recorded. Fasting blood samples were drawn from the elbow vein to measure hormone levels including total testosterone (TT), sex hormone-binding globulin (SHBG), fasting plasma glucose (FPG), fasting insulin (FINS), lipids, and homocysteine (Hcy). The insulin resistance index (HOMA-IR) and free androgen index (FAI) were calculated. Ultrasound elastography was used to measure the IMT and elastic function parameters of the right carotid artery, including vessel diameter, wall displacement, stiffness coefficient, and pulse wave velocity. Differences in various parameters between the two groups were analyzed, and correlations between the carotid stiffness coefficient and other serological indicators were assessed using Spearman correlation analysis. Results: No significant differences in age, body mass index, heart rate, systolic blood pressure, and diastolic blood pressure were observed between the two groups (all P>0.05), while the waist-to-hip ratio (WHR) was higher in the case group than in the control group (P<0.05).The hormone level serological indicators TT and FAI were higher in the case group than in the control group, and SHBG was lower in the case group than in the control group (all P<0.05). The metabolism-related serum indicators LDL-C, HDL-C, FPG, triglycerides, and total cholesterol levels were not statistically different between the two groups (all P>0.05), and serum FINS, HOMA-IR, and Hcy levels were significantly higher in the case group than in the control group (all P<0.05).No significant difference in carotid artery diameter was observed between the case group and control group (P>0.05). The carotid artery displacement in the case group was significantly smaller than that in the control group (P<0.05), and carotid IMT, hardness coefficient, and pulse wave propagation velocity were greater in the case group than in the control group (all P<0.05). The carotid elastic stiffness coefficient was positively correlated with WHR, TT, SHBG, FAI, FINS, HOMA-IR and Hcy to varying extents and negatively correlated with SHBG. Conclusion: In non-obese PCOS patients with no metabolic or cardiovascular disease, the carotid stiffness coefficient was increased and correlated with indicators of hyperandrogenism, insulin resistance, and hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a hormonal disorder that affects 6–12% of United States women of reproductive age. Because women with PCOS are at an increased risk of developing type 2 diabetes, clinical practice guidelines from a number of organizations (e.g. American Diabetes Association, American College of Obstetricians and Gynecologists, US Preventive Services Task Force) recommend that individuals with PCOS are routinely screened for diabetes. Guidelines further indicate that an oral glucose tolerance test (OGTT) should be used for diabetes screening in women with PCOS as opposed to an A1C or fasting plasma glucose test. The purpose of this study is two-fold: 1) to estimate rates of diabetes screening among a nationwide sample of commercially insured women with PCOS and 2) to report the percentage of women screened using each test (OGTT, A1C, fasting plasma glucose) among those who were screened. Methods: We used the MarketScan Commercial Claims database (2011–2019) to identify a sample of women aged 18–64 years with PCOS who were free from diabetes at baseline and had ≥ 5 years of continuous enrollment in their insurance plan. PCOS was ascertained using International Classification of Disease diagnosis codes (ICD-9: 256.4; ICD-10: E28.2). Diabetes screening was ascertained using Current Procedural Terminology (CPT) codes (A1C: 8303683037; Fasting blood sugar: 82947; OGTT: 82950). Diabetes screening rates were calculated for the overall study sample as well as across subgroups defined by age, overweight/obesity, hypertension, hypercholesterolemia, and vascular disease. Results: In our sample of 191,110 commercially insured women with PCOS, 73.40% were screened at least once for diabetes during a five-year period. Among the women screened, 19.24% were screened using the Androgen Excess Society (AES)-recommended OGTT, 61.58% were screened using A1C, and 23.37% were screened using fasting blood sugar. Conclusions: In a sample of commercially insured individuals spanning the timeframe 2011–2019, nearly 75% of women with PCOS complied with the ACOG screening guidelines for diabetes. Although OGTT is recommended as the preferred screening tool for women with PCOS it was less commonly used than A1C and fasting blood sugar tests. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) are androgen excess disorders requiring the determination of classic androgen levels for diagnosis. 11-oxygenated androgens have high androgenic potential, yet their clinical value in those disorders is not clear. Additionally, the role of endocrine disruptors (EDs), particularly in IH, remains understudied. We analyzed 25 steroids and 18 EDs in plasma samples from women with IH, PCOS, and controls using LC-MS/MS. Cytokine levels and metabolic parameters were assessed. Comparisons included non-obese women with PCOS (n = 10), women with IH (n = 12) and controls (n = 20), and non-obese versus obese women with PCOS (n = 9). Higher levels of 11-oxygenated androgens were observed in women with PCOS compared to those with IH, but not controls. Conversely, 11-oxygenated androgen levels were lower in women with IH compared to controls. Cytokine levels did not differ between women with IH and controls. Bisphenol A (BPA) levels were higher in obese women with PCOS compared to non-obese women with PCOS. Bisphenol S occurrence was higher in women with PCOS (90%) compared to controls (65%) and IH (50%). Significant correlations were found between androgens (11-ketotestosterone, androstenedione, testosterone) and insulin and HOMA-IR, as well as between immunomodulatory 7-oxygenated metabolites of DHEA and nine interleukins. Our data confirms that PCOS is a multiendocrine gland disorder. Higher BPA levels in obese women might exacerbate metabolic abnormalities. IH was not confirmed as an inflammatory state, and no differences in BPA levels suggest BPA does not play a role in IH pathogenesis. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a gynecological disorder among reproductive-aged women and a major cause of infertility. Different treatment options are being employed but with side effects. This has mandated alternative treatment options, especially complementary therapy. This study therefore investigated the possible protective effects of methanol extract of Drymaria cordata in Letrozole-induced PCOS. The plant is folklorically used in the treatment of diverse ailments including PCOS, fibroids, uterine/ovarian/breast tumors, and cancers. Forty-eight female Wistar rats were acclimatized and initially divided into two groups: group I(control group) and group II(PCOS group). PCOS was induced by the oral administration of letrozole/high-fat diet for 21 days. After the induction, the PCOS group was sub-divided into four groups (n = 4): group II (positive control with PCOS), group III (MET 2mg/kg), group IV (MEDC 200mg/kg), and group V (MEDC 400mg/kg). Rats were orally treated with MET and MEDC for six weeks after the PCOS induction. At the end of the experimental period, blood samples were collected, sera were separated, mitochondria were isolated, and the mPT, some apoptotic biomarkers, hormonal and lipid profiles, and oxidative stress markers were determined. Ovarian histological evaluation and GC–MS analysis of MEDC were carried out. There was no significant mPT pore opening in the PCOS (untreated) group. However, treatments with MEDC caused significant mPT pore opening, upraised caspase 9, caspase 3, and Bax, and decreased anti-apoptotic Bcl-2 levels. The MEDC treatments restored the hormonal and lipid profiles, increased the levels of GSH-Px and SOD and decreased TBARS. Histological examination revealed resolved ovarian cysts and improved follicular growth with MEDC treatments. Comparable results were observed for both MEDC and metformin. The GC–MS analysis revealed the presence of some major pharmacologically relevant compounds. These findings suggest that MEDC contains phytochemicals that can protect against letrozole-induced PCOS possibly by normalizing the impaired hormonal balance, restoring the lipid profile, and improving the antioxidant milieu of the system. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common reproductive and endocrine disorders in women of childbearing age, and the pathogenesis is unknown. Insulin resistance, hyperandrogenism and obesity are important pathophysiological basis. Glucose-dependent insulinotropic peptide (GIP) is a gastrointestinal hormone involved in the regulation of insulin secretion. Literature studies have shown that GIP is correlated with insulin resistance, hyperandrogenism, obesity and other characteristic changes of PCOS, and it may contribute to the onset and progression of PCOS by affecting the function of hypothalamic-pituitary-ovarian axis, suggesting that GIP is associated with PCOS. This paper reviews the research progress of the correlation between GIP and PCOS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings. [ABSTRACT FROM AUTHOR]

Ovarian hyperthecosis (OHT) is a rare cause of severe hyperandrogenism in the adolescent age group. We describe two case reports, and present an approach to management in this age group based on a review of the literature. Patient A presented at age 13 years with a 2 year history of androphonia and hirsuitism. Her testosterone level was elevated at 8.3 nmol/L, and there was marked enlargement of her ovaries bilaterally. There were no focal adrenal or ovarian lesions identified on imaging. She was treated with a gonadotropin releasing hormone (GnRH) agonist and spironolactone with biochemical and clinical improvement. Patient B presented at age 14 years with secondary amenorrhoea, and a 2 year history of androphonia, hirsutism and androgenetic alopecia. Her testosterone level was 12 nmol/L, and a pelvic ultrasound revealed numerous follicles in each ovary which were otherwise normal in size. She was managed with GnRH agonist initially, and now continues on a combined oral contraceptive pill. Ovarian hyperthecosis needs to be considered in pre-menopausal women presenting with severe hyperandrogenism, after exclusion of androgen-producing adrenal and ovarian tumours. The principles of management in this age group are gonadotropin suppression and hormone replacement. [ABSTRACT FROM AUTHOR]

Introduction: In females with congenital adrenal hyperplasia (CAH), the influence of hyperandrogenism and glucocorticoid supplementation on neurocognition is controversial. Objectives: To identify possible differences in visual working memory and verbal memory in adolescent girls with CAH due to 21-hydroxylase deficiency and matched controls. Moreover, to study if any relationship between variables associated with CAH and the scores of the selected memory tests was present. Material and methods: In total 39 individuals were studied, female adolescents with CAH and age and pubertal stage matched healthy male and female controls (13 in each group). Sociodemographic, clinical, hormonal, and neurocognitive variables were explored. In female adolescents with CAH, variables related to the disease (age at diagnosis, clinical form, time since diagnosis, and glucocorticoid doses) were correlated with the scores obtained for neurocognitive variables. Results: The mean age was 13.9 ± 3.3 years. In female adolescents with CAH the results were worse compared to controls in Free Recall (p = 0.039) and in Visual Memory Span score (p = 0.016). Age at diagnosis was negatively correlated to number of hits (p = 0.04), number recalled backward (p = 0.03), Visual Memory Span test score (p = 0.04) and Total Free Recall (p = 0.04), i.e., memory was worse with later diagnosis. Conclusions: Female adolescents with CAH had worse visual working memory compared to matched controls, but not in verbal memory. Age at diagnosis was negatively associated with the memory tests. [ABSTRACT FROM AUTHOR]

Abstract Insulin resistance (IR) is a well-recognized covariate of Polycystic Ovarian Syndrome (PCOS) with varying burden and risk factors among populations. The relationship of insulin secretory defect or ISD with PCOS is less understood. The presence of IR and ISD as well as their covariates have been explored in the present case-control study among young adult to early middle-aged, normal weight to obese, Bangalee women with PCOS. A number of 158 PCOS [age 23 (15–34) years, Median (Range)] and 126 Non-PCOS [24 (19–34) years] females were recruited purposively with PCOS diagnosed following Modified Rotterdam Criteria 2003. Hormones were measured by CLIA method and lower abdominal ultrasonography was done by trained personnel. IR and ISD were assessed by homeostasis model assessment with 75th percentile values of HOMA-IR (2.4) and HOMA%B (143) in Non-PCOS group considered as the cut-off values. Hyperandrogenism (HA) was measured by calculating Fasting Androgen Index (FAI). HOMA-IR was high among 52% of PCOS and 28% of Non-PCOS women. Body Mass Index (BMI) and HA were independently associated covariates of IR (p

Introduction. Previously, it was shown that the “classic” phenotypes of polycystic ovarian syndrome (PCOS) are associated with significant decrease in gut microbiota alpha diversity as compared with healthy women.The aim of the study. To establish cut-off points for alpha diversity indices, significant in polycystic ovarian syndrome with hyperandrogenism.Material and methods. The manuscript presents a sub-study of Eastern Siberia PCOS Epidemiology and Phenotype Study, conducted in Eastern Siberia (Russia) from 2016 to 2019. All participants (175 women of reproductive age: 26 women with PCOS (according to Rotterdam criteria (2003)) and hyperandrogenemia (increased levels of total testosterone (TT) and/or free androgenindex(FAI), and/ordehydroepiandrosterone sulphate (DHEAS)), 149 – without hyperandrogenemia) were recruited during the annual employment medical assessment. Methods included a questionnaire survey, anthropometry and modified Ferriman – Gallwey score, gynecological examination, pelvic ultrasound, and blood serum tests for TT, DHEAS, sex hormone-binding globulin, FAI, prolactin, thyroid-stimulating hormone, and 17-hydroxyprogesterone. Five indices of alpha diversity (amplicon sequencing variant, Shannon index, Simpson index, Chao index, and abundance-based coverage Index) were estimated for the gut microbiota using amplicon metasequencing. Statistical analysis included ROC-analysis for development of cut-off points for the indices, associated with hyperandrogenism in women of reproductive age with PCOS. Results. According to results of ROC-analysis, the greatest sensitivity with moderate specificity, with a high area under the curve was established for the Shannon and Simpson indices with cut-off points classifying women with or without hyperandrogenemia – 5.84 and 0.97, respectively.Conclusions. The developed criteria for assessing alpha diversity using cut-off points for the most significant indices can be useful for monitoring the results of different therapeutic interventions (prebiotics, probiotics, etc.) in hyperandrogenic phenotypes of PCOS.

Abstract Background Polycystic ovarian syndrome (PCOS) is a common endocrine disorder affecting one in five women of reproductive age. Polycystic appearance of the ovaries in ultrasonography is associated with oligomenorrhea, and clinical and or biochemical hyperandrogenism. PCOS has been associated with voice alterations for many years. However, there is insufficient research on voice analysis in PCOS patients. Objectives This research aimed to examine the voice characteristics among women with PCOS. Patients and methods Our study included 25 women confirmed with PCOS and 25 control. A complete voice assessment was performed for all participants using primary demographic data, vocal symptoms, auditory perceptual evaluation of the voice, Arabic version of the Voice Handicap Index, acoustic analysis, and video laryngoscopic examination of the larynx. Results Our study revealed statistically significant differences between PCOS and control groups in phonasthenic symptoms, auditory perceptual assessment of the voice, acoustic parameters, and laryngoscopic examination. Conclusion PCOS women with hirsutism are complaining of vocal symptoms, changes in vocal characters, and deterioration of the acoustic parameters of the voice. High serum levels of androgen can cause the deepening of the voice, which is essential for the early detection of vocal symptoms in PCOS patients to prevent virilization of their voice. Trial registration NCT06085170. Registered 20 August 2023—retrospectively registered, https://www.google.com/url?sa=t&source=web&rct=j&opi=89978449&url=https://classic.clinicaltrials.gov/ct2/show/NCT06085170&ved=2ahUKEwjEyLqUq6KGAxWxRPEDHb57DIQQFnoECBQQAQ&usg=AOvVaw1xTurnA6mJEZ9PK0vQS8VL .

Clitoral enlargement (clitoromegaly) due to non-hormonal causes, particularly due to vascular malformation, is rare. Only eight such cases are reported in the literature. We report an additional case of isolated vascular malformation implicating the clitoris of a young girl child and its surgical management.

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

Abstract Introduction 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. Materials and 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. Conclusion 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.

INTRODUCTION. Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Clinical practice guidelines on PCOS recommend combined oral contraceptives (COCs) as first-line therapy. Given the association of PCOS with a number of clinical conditions, including obesity, type 2 diabetes mellitus, metabolic syndrome, anxiety and depressive disorders, an increased risk of endometrial cancer, and cardiovascular diseases, it is important to describe and systematise data on the benefits and risks associated with COCs.AIM. This study aimed to review current data on the use of COCs in PCOS, focusing on the rationality of prescribing, the main risks of using COCs, and the measures to minimise these risks.DISCUSSION. Hirsutism is the most prominent clinical manifestation of hyperandrogenism; in PCOS, its prevalence is 65–75%. COCs containing progestins with anti-androgenic properties are effective in treating hirsutism and superior to anti-androgens alone. Women with PCOS are at increased risk of endometrial cancer due to prolongation of the oestrogen-dependent proliferative phase. This risk can be mitigated by the normalising effect of COCs on the menstrual cycle and the effect of the progestin component of COCs. This review highlights the controversial nature of data on the association of COCs with emerging or exacerbating mental disorders, impaired glucose tolerance, and arterial hypertension/other cardiovascular risks in PCOS. Since the main safety issue with COCs is their thrombogenicity, clinicians should take special care when prescribing medicinal products from this group to PCOS patients. Data on the effect of COCs on fertility in women with PCOS are limited, but there is published evidence of an adverse effect of long-term use of COCs on the results of assisted reproductive technologies.CONCLUSIONS. The key benefit of the non-contraceptive use of COCs in PCOS is in treating hyperandrogenism, mainly hirsutism. To achieve effect, the patient should take COCs containing progestins with anti-androgenic properties for at least 6 months. PCOS patients can also use COCs for contraception. Clinicians prescribing COCs to women with PCOS should consider the individual patient context, the aim of treatment, and any potential risks associated with COCs.

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.

Background: A combination of genetic and environmental factors contribute to the highly common, complex, and varied endocrine condition known as polycystic ovary syndrome (PCOS) in women. PCOS primarily affects women between the ages of 15 and 35 who are in the early to late stages of pregnancy. Thus, this study aimed to evaluate the serum levels of irisin, subfatin, and adropin in PCOS with and without obesity compared to the control group.Methods: The present cross-sectional study was conducted in 2022 at Al-Nahrain University/Department of Chemistry (Baghdad, Iraq). The serum levels of irisin, subfatin, and adropin were measured with the enzyme-linked immunosorbent assay (ELISA) method. Body mass index, lipid profile, insulin, fasting glucose, follicle-stimulating hormone, and luteinizing hormone levels were also evaluated. The data were analyzed using one-way analysis of variance (ANOVA) by GraphPad Prism software version 8.0.2. A P

Predominantly androgen secreting juvenile granulosa cell tumors (JGCT) are uncommon and few reports have been published. We present a case of a JGCT that presented with signs of prepubertal hyperandrogenism and insulin resistance to highlight the possible interaction between hyperandrogenemia and hyperinsulinism. A 4-year-old girl presented with acanthosis nigricans and hyperinsulinism, mimicking the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome at an age much younger than is typical for this diagnosis. Laboratory studies revealed elevated insulin, inhibin A and B, and total testosterone. All laboratory results normalized after unilateral salpingo-oophorectomy. The final diagnosis was Stage 1A JGCT. This case highlights the importance of including ovarian tumors in the differential diagnosis when considering causes of virilization and insulin resistance. This case also suggests a potential relationship between excess testosterone secretion and hyperinsulinemia and strengthens evidence that hyperandrogenemia may promote hyperinsulinism in ovarian disease.

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies among young women. Ultrasound evidence of polycystic ovaries is one of its crucial diagnostic criteria. Objectives: Our main objective is to study the contribution of ultrasound data in diagnosing PCOS. In addition, we aim to establish a new cutoff point for the use of ultrasound and to determine its sensitivity as well as its specificity. Design: It was a prospective study, including all patients presenting with clinical hyperandrogenism. Methods: The ultrasound examination of these patients was performed using a novel ultrasound machine (18 MHz) compared to an older ultrasound machine (2 Hz–8 MHz). Inclusion criteria encompassed adult female patients over 18 years presenting symptoms suggestive of PCOS, particularly hyperandrogenism and oligo-anovulation, meeting Rotterdam's diagnostic criteria. Prior to inclusion, assessments were conducted to eliminate other potential causes explaining hyperandrogenism or menstrual disorders in both groups. Results: We examined 92 patients diagnosed with PCOS. Menstrual disorders were the main symptoms, with amenorrhea being more frequent in the PCOS group (G1) (48.9% vs the control group (G2): 11.1%). The follicle number was significantly lower in the control group, as assessed by both ultrasound machines (p < 10−3). The accuracy of the new ultrasound device was evaluated compared to the old one using the receiver operating characteristic (ROC) curve, revealing a cutoff of 18 follicles (sensitivity of 68.1%, specificity of 100%) and an area under the curve of 0.955. We found a significant difference between the median values of the number of follicles (NF) by both ultrasound machines (18 vs 12). It was positively correlated with an index of r = 0.916. For the volume, it was distinctively higher in G1 (p < 10−3). ROC curve analysis revealed an ovarian volume cutoff of 9.25 ml with a sensitivity of 48.9% and a specificity of 100%. Both ultrasound machines were positively correlated with an index of r = 0.979 (p < 10−3). Conclusion: In conclusion, we were able to establish significant correlations between the new and the old ultrasound devices for both the NF and ovarian volume. Our study is distinctive as it represents the first on the African continent to re-evaluate the ultrasound criterion for PCOS. Plain language summary: Validating ultrasound criteria for PCOS in North African patients In this study, we explored patients using ultrasound to better diagnose Polycystic Ovary Syndrome (PCOS) in North African women. Ovarian follicles are small sacs in a woman's ovaries that not only release eggs but also produce important hormones like estrogen and progesterone. These hormones regulate the menstrual cycle, prepare the body for pregnancy, and influence many aspects of a woman's health and well-being. We set new standards for measuring follicles and ovaries to improve diagnosis accuracy. Background: Polycystic Ovary Syndrome (PCOS) is often diagnosed using ultrasound in North African women. Current ultrasound standards may not be accurate enough for this group. This study aimed to improve PCOS diagnosis by setting new standards for measuring ovarian sizes and follicle numbers. Methods: We reviewed a new ultrasound method. We then established new measurement thresholds specific to North African women. These new standards were tested for accuracy in diagnosing PCOS. Results: Our new measurement thresholds were more accurate in diagnosing PCOS. The improved standards led to better identification of PCOS in North African women. This suggests that current ultrasound methods might need adjustments based on population-specific data. Conclusions: Using ultrasound with new measurement standards can improve PCOS diagnosis in North African women. Adjusting diagnostic criteria to specific populations may enhance overall healthcare outcomes. [ABSTRACT FROM AUTHOR]

Introduction: 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. Materials and 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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 (ODHA 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. Results: 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 ODPCOM 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 ODHA 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). Conclusion: 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 longterm complications. [ABSTRACT FROM AUTHOR]

Cardiovascular dysfunctions complicate 10–20% of pregnancies, increasing the risk for postpartum mortality. Various gestational insults, including preeclampsia are reported to be associated with adverse maternal cardiovascular outcomes. One such insult, gestational hyperandrogenism increases the risk for preeclampsia and other gestational morbidities but its impact on postpartum maternal health is not well known. We hypothesize that gestational hyperandrogenism such as testosterone (T) excess will adversely impact the maternal heart in the postpartum period. Pregnant ewes were injected with T propionate from day 30 to day 90 of gestation (term 147 days). Three months postpartum, echocardiograms, plasma cytokine profiles, cardiac morphometric, and molecular analysis were conducted [control (C) n = 6, T-treated (T) n = 7 number of animals]. Data were analyzed by two-tailed Student's t test and Cohen's effect size (d) analysis. There was a nonsignificant large magnitude decrease in cardiac output (7.64 ± 1.27 L/min vs. 10.19 ± 1.40, P = 0.22, d = 0.81) and fractional shortening in the T ewes compared with C (35.83 ± 2.33% vs. 41.50 ± 2.84, P = 0.15, d = 0.89). T treatment significantly increased 1) left ventricle (LV) weight-to-body weight ratio (2.82 ± 0.14 g/kg vs. 2.46 ± 0.08) and LV thickness (14.56 ± 0.52 mm vs. 12.50 ± 0.75), 2) proinflammatory marker [tumor necrosis factor-alpha (TNF-α)] in LV (1.66 ± 0.35 vs. 1.06 ± 0.18), 3) LV collagen (Masson's Trichrome stain: 3.38 ± 0.35 vs. 1.49 ± 0.15 and Picrosirius red stain: 5.50 ± 0.32 vs. 3.01 ± 0.23), 4) markers of LV apoptosis, including TUNEL (8.3 ± 1.1 vs. 0.9 ± 0.18), bcl-2-associated X protein (Bax)+-to-b-cell lymphoma 2 (Bcl2)+ ratio (0.68 ± 0.30 vs. 0.13 ± 0.02), and cleaved caspase 3 (15.4 ± 1.7 vs. 4.4 ± 0.38). These findings suggest that gestational testosterone excess adversely programs the maternal LV, leading to adverse structural and functional consequences in the postpartum period. NEW & NOTEWORTHY: Using a sheep model of human translational relevance, this study provides evidence that excess gestational testosterone exposure such as that seen in hyperandrogenic disorders adversely impacts postpartum maternal hearts. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting approximately 5 to 18% of women of reproductive age and 3 to 11% of teenagers. The diagnostic criteria used in adult patients are not suitable for the diagnosis of adolescent patients, because some of the features may be physiological for puberty, so research is still ongoing to improve the criteria for diagnosing PCOS in teenagers. Polycystic ovary syndrome is associated with hormonal and metabolic changes and may predispose to the occurrence of many other diseases, such as obesity, metabolic syndrome, hypertension, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Due to the high prevalence of PCOS and the various health problems it brings, it is necessary to select adolescent girls from the risk group, make an efficient diagnosis, start appropriate treatment, and lead the patient through a lifestyle change as soon as possible. Researchers' attention is increasingly focused on patients presenting with PCOS already in their teenage years. In our work, we want to look at the latest reports regarding the prevalence, pathophysiology and diagnosis of PCOS in adolescent girls. [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]

AbstractContextObjectiveMethodsResultsConclusionsPolycystic ovary syndrome (PCOS) is an endocrine gynaecological disorder that affects many women of childbearing age.To evaluate the efficacy and safety of glucose-like peptide-1 receptor agonists for obese women with PCOS.We searched the PubMed, Embase, WOS, and Cochrane Libarary databases up to June 2023. Studies were eligible if they were randomised controlled trials (RCTs) comparing GLP-1RAs against any other treatments for patients with PCOS.Overall, a total of 8 RCTs were included in this review, 7 of the RCTs compared GLP-1RAs with metformin, and 1 RCT compared GLP-1Ras with dapagliflozin. Compared with control group, GLP-1RAs were more effective at improving insulin sensitivity, reducing BMI, and resulting in a smaller waist circumference.GLP-1RAs may be a good option for obese women with PCOS, especially those with insulin resistance. However, high-quality studies are also needed in the future to assess the efficacy of GLP-1RAs in women with PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is associated with a low‐grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a PCOS‐like mouse model, it is demonstrated that hyperandrogenism affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site‐specific manner. Co‐treatment with an androgen receptor antagonist prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)‐exposed mice displayed a drastically reduced eosinophil population in the uterus and visceral adipose tissue (VAT). A higher frequency of natural killer (NK) cells and elevated levels of IFN‐γ and TNF‐α are seen in uteri of androgen‐exposed mice, while NK cells in VAT and spleen displayed a higher expression level of CD69, a marker of activation or tissue residency. Distinct alterations of macrophages in the uterus, ovaries, and VAT are also found in DHT‐exposed mice and can potentially be linked to PCOS‐like traits of the model. Indeed, androgen‐exposed mice are insulin‐resistant, albeit unaltered fat mass. Collectively, it is demonstrated that hyperandrogenism causes tissue‐specific alterations of immune cells in reproductive organs and VAT, which can have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS. [ABSTRACT FROM AUTHOR]