Obese Polycystic Ovary Syndrome Women Research Articles

Polycystic Ovary Syndrome, Insulin Resistance, and Cardiovascular Disease.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events. IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.

A Cross-Sectional Study of Protein Changes Associated with Dementia in Non-Obese Weight Matched Women with and without Polycystic Ovary Syndrome.

Dysregulated Alzheimer's disease (AD)-associated protein expression is reported in polycystic ovary syndrome (PCOS), paralleling the expression reported in type 2 diabetes (T2D). We hypothesized, however, that these proteins would not differ between women with non-obese and non-insulin resistant PCOS compared to matched control subjects. We measured plasma amyloid-related proteins levels (Amyloid-precursor protein (APP), alpha-synuclein (SNCA), amyloid P-component (APCS), Pappalysin (PAPPA), Microtubule-associated protein tau (MAPT), apolipoprotein E (apoE), apoE2, apoE3, apoE4, Serum amyloid A (SAA), Noggin (NOG) and apoA1) in weight and aged-matched non-obese PCOS (n = 24) and control (n = 24) women. Dementia-related proteins fibronectin (FN), FN1.3, FN1.4, Von Willebrand factor (VWF) and extracellular matrix protein 1 (ECM1) were also measured. Protein levels were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Only APCS differed between groups, being elevated in non-obese PCOS women (p = 0.03) relative to the non-obese control women. This differed markedly from the elevated APP, APCS, ApoE, FN, FN1.3, FN1.4 and VWF reported in obese women with PCOS. Non-obese, non-insulin resistant PCOS subjects have a lower AD-associated protein pattern risk profile versus obese insulin resistant PCOS women, and are not dissimilar to non-obese controls, indicating that lifestyle management to maintain optimal body weight could be beneficial to reduce the long-term AD-risk in women with PCOS.

Association of Neuregulin-4 levels and body mass index with hyperandrogenism in Polycystic Ovary Syndrome patients

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine and metabolic disease that affects approximately 15% of women of childbearing age worldwide. It is one of the causes of infertility and is characterized by hirsutism, acne, persistent or interrupted anovulation, and hyperandrogenemia. Neuregulin-4 (NRG-4) is an adipokine hormone from the protein neuregulin family. Its level is greater in PCOS than in control women, and Neuregulin-4 is linked to body fat percentage and liver fat, as well as insulin resistance (IR). Objectives: To estimate the serum NRG-4 levels in women diagnosed with (PCOS), to compare it with, non-PCOS healthy control and to explore the effect of hyperandrogenism on the obtained result. Patients and Methods: A case-control study was conducted in the Gynecology and the Infertility Clinics in Kut - Zahraa Hospital, Medical City, from September to December 2022. The study included 120 women aged (18-42) years, 60 of whom were diagnosed with polycystic ovaries, and the other 60 were in the control group. Results: Women with PCOS had a significantly higher NRG-4, LH, LH/FSH ratio, testosterone, free testosterone, and Dehydroepiandrosterone sulfate (DHEA-S) than the control groups. In this study, NRG-4 was significantly higher in obese and overweight PCOS women than in normal-weight women. Conclusion: The mean serum NGR-4 concentration is significantly increased in women with PCOS and could be a part of metabolic syndrome. NGR-4 levels were associated with obesity, hyperandrogenism (testosterone, free testosterone, and DHAES) and may have a role in the development of PCOS. Received: May,, 2022 Accepted: Oct, 2023 Published: Jan.2024

Altered Vitamin D Status and Bone Mineral Density in Obese and Non-obese Patients With Polycystic Ovary Syndrome: A Cross-Sectional Study in Turkey.

Background Polycystic ovary syndrome (PCOS) is the most common endocrinological disease in women of reproductive age. In addition to providing the basis for comorbidities such as metabolic and cardiovascular diseases, it also affects bone metabolism. This study aimed to determine whether there is a relationship between bone mineral density (BMD), vitamin D status, insulin resistance, sex hormones, and calcium metabolism disorders in women with PCOS. Methodology Fifty-six non-obese women with PCOS, 67 obese women with PCOS, and 45 normal weight controls participated in the study. Circulating levels of gonadotropins, estradiol, prolactin, dehydroepiandrosterone sulfate, total testosterone, thyroid stimulating hormone, sex hormone-binding globulin, insulin, glucose, and calcium metabolism parameters were assessed. We used the Homeostatic Model Assessment-Insulin Resistance Index to detect insulin resistance. BMD values in the various body regions were measured by dual X-ray absorptiometry. Results Women with PCOS had significantly lower vitamin D values and lumbar spine BMD than controls (p <0.001 and p <0.05, respectively). Among the patients with PCOS subgroups, vitamin D deficiency (VDD) was more frequent in obese PCOS patients (67.1%) than in non-obese patients (58.9%). We found significantly lower BMD at all sites only in the subgroup of the non-obese PCOS women than in controls (p <0.001). Conclusions VDD is prevalent in PCOS women in those with obesity and hyperandrogenemia. Non-obese PCOS women have significantly lower BMD measurements than healthy controls, but obese PCOS women have BMD values comparable with normal-weight eumenorrheic controls. Body mass index is the most important factor determining BMD in women with PCOS.

Body mass index is a good predictor of metabolic abnormalities in polycystic ovary syndrome.

To assess which parameters among hyperandrogenism (total testosterone-tT-or free androgen index-FAI), sex hormone binding globulin (SHBG) or body mass index (BMI) could better predict a worse metabolic profile in women with polycystic ovary syndrome (PCOS). Five hundred and eighty-six women with PCOS and clinical or biochemical hyperandrogenism were included. Receiver Operating Characteristics (ROC) curves with tT, FAI, SHBG and BMI were performed for metabolic parameters and a cut-off with sensitivity and specificity was obtained for each parameter. The women were then divided into three groups and compared according to their BMI. Based on the ROC curves, tT proved not to be a good predictor of metabolic alterations. FAI and SHBG resulted to be good predictors of some markers of metabolic damage. The area under the curves (AUC) of SHBG were greater than those of FAI. SHBG levels affects the values of homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, high density lipoproteins (HDL), low density lipoproteins (LDL), and total cholesterol also when corrected for BMI. However, the highest AUCs of the ROC curves were observed when BMI was used, which was significantly related to all the metabolic parameters analyzed. Dividing women according to their BMI, BMI between 25.00 and 30.00 kg/m2 had a worse metabolic profile but still in a normal range, while BMI≥30 kg/m2 women had a significant metabolic derangement. BMI is a good predictor factor of metabolic changes in PCOS women at any age, and obesity is associated to the appearance of metabolic complications. Overweight and obese PCOS women should be addressed to perform a complete metabolic assessment.

Successful Pregnancy in Morbidly Obese Women of Polycystic Ovary Syndrome With Various Treatment Options With Individual Consequences: Case Series

Objective: The objective of the study was to compare the effectiveness of different treatment options in the management of infertility across three cases in morbidly obese women with polycystic ovary syndrome (PCOS). Case study &amp; results: The first case is 30 years old with secondary infertility for two years with two abortions and a body mass index (BMI) is 69, she tried all lifestyle modifications with no response to weight reduction and she was conceived spontaneously without fertility treatment and subsequent antenatal care progressed without any complications until 36 weeks complicated with raised blood sugar beyond the normal level but not so high and intrauterine fetal death one week later ended by spontaneous normal vaginal delivery. The second case is 24 years old with BMI 66 is undergone weight reduction, ovulation induction with clomiphene citrate and gonadotropin injections with good ovulation response but no pregnancy, in vitro fertilization was performed but aborted at 8 weeks gestation, one year later after the use of metformin and ovulation induction with injections patient conceived and her pregnancy complicated by pre-eclampsia, gestational diabetes treated with insulin and preterm delivery. The third case is 40 years old with primary infertility for 5 years with BMI 70, she is known case diabetes mellitus 10 years back controlled with insulin, and hypertension on treatment, undergone bariatric surgery and one year later IVF was done after the failure of multiple ovulation induction, her diabetes mellitus and hypertension control well with treatment and delivered at 39 weeks by elective cesarean section with a birth weight of 4.5 kg. Discussion: PCOS is a genetic condition, worsened by obesity. The prevalence of obesity in PCOS women is up to 80%. There is a strong relationship between PCOS and obesity making the condition more complex. The majority of women with PCOS are either overweight or obese and the pathogenesis of obesity in PCOS has not yet been exactly identified. Obesity has adverse effects on fertility through anovulation, poor implantation, and quality oocyte. Conclusion: The ideal treatment of infertility in morbidly obese PCOS women has not been defined, but generally, before deciding which treatment option is preferred, proper weight loss and control of the metabolic state are carried out for successful pregnancy

Short-term and low-dose liraglutide plus metformin decreased body mass index and insulin resistance more than metformin alone in obese women with polycystic ovary syndrome: An open-label randomized controlled study

Background and objectives: Reduction of weight improves different manifestations of polycystic ovary syndrome (PCOS). This study compared the effects of liraglutide plus metformin versus metformin alone on weight loss and metabolic profiles in obese women with PCOS. Methods: This open-label randomized controlled clinical trial consecutively recruited newly-diagnosed PCOS patients of reproductive age with obesity (body mass index ≥ 27.5 kg/m2). Following randomization into two equal groups, Group-1 received treatment with metformin 1000 mg daily alone while Group-2 was given metformin 1000 mg plus subcutaneous (SC) liraglutide 1.2 mg daily for 12 weeks. Anthropometric, biochemical and hormonal data and ovarian morphology were assessed at baseline and after 12 weeks. Clinical information and side effects were recorded every four weeks after initiation of the treatment. Glucose, lipids, and all hormones were analyzed by glucose oxidase, precipitation method, and chemiluminescent microparticle immunoassay respectively. Insulin resistance was measured by homeostatic model assessment (HOMA-IR). Results: Study included 30 participants comprising 15 for each group. Among 15 participants, 5 dropped out from the Group-1 and 1 dropped out from the Group-2. The final analysis was done among 24 participants (Gr-1: 10 and Gr-2: 14). Waist and hip circumference (WC, HC) significantly (p &lt;0.05) decreased in patients treated with only metformin. Menstrual irregularity, BMI (body mass index), HC, systolic blood pressure (BP), 2h-OGTT glucose, fasting insulin, and HOMA-IR significantly (p &lt; 0.05) decreased in the patients of Group-2 after 12 weeks compared to baseline status. Percentage changes of weight, BMI and HOMA-IR improved significantly (p &lt; 0.05) in cases of Group-2 than those in Group-1. Side effects were though numerically higher in the Group-2 patients, but reduced with time. Conclusions: Addition of liraglutide with metformin was superior to metformin alone for lowering of BMI and insulin resistance among obese PCOS women with acceptable side effects. IMC J Med Sci. 2024; 18(1):002. DOI: https://doi.org/10.55010/imcjms.18.002 *Correspondence: Muhammad Abul Hasanat, Room# 1524, Level-15, Block-D, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka-1000, Bangladesh. ORCID iD: orcid.org/0000-0001-8151-9792; Email: aryansowgat@gmail.com

1679-P: L-arginine Ameliorates Polycystic Ovary Syndrome and Attenuates Intestinal Oxidative Stress by Regulating Gut Microbiota

More than half of Polycystic ovary syndrome (PCOS) women are overweight or obese, and weight gain amplifies and worsens the symptoms of PCOS. Hence, it is essential to further understand and treat PCOS women with obesity. Therefore, this study tried to use a multi-omics approach that integrates the gut microbiome, serum metabolomics, serum transcriptomics, and clinical indicators to distinguish obese PCOS from obese non-PCOS women. The stool and blood samples from 33 obese PCOS patients and 30 obese control women were collected. The sequencing results suggested there were significant differences in gut microbiome and metabolites between obese PCOS women and obese women. Of which, the level of L-arginine (Arg) in obese PCOS patients was significantly lower than that in the control group and associated with gut microbiota alterations. Further correlation analysis between metabolite and clinical phenotype showed that Arg was significantly correlated with the clinical phenotype of obese PCOS patients. In this study, C57BL/6 mice were treated with dehydroepiandrosterone (DHEA) with a high-fat diet (HFD) to induce obese PCOS mice models for 3 weeks. PCOS mice were randomly divided into four groups: Arg group, Arg + antibiotic cocktail (ABX) group, PCOS group, and PCOS + ABX group. After 3 weeks of Arg supplementation, the estrous cycle, ovarian morphology, intestinal oxidative stress and intestinal barrier integrity were improved in Arg group PCOS mice, while testosterone levels and insulin resistance levels were decreased. However, these improvements were not observed in the Arg plus ABX group, suggesting that ABX-mediated depletion of the gut microbiome would eliminate these improvements. Then the 16s rRNA sequencing was performed to determine the gut microbiota of the four groups. The results showed that Arg can ameliorate reproductive characteristics of PCOS and attenuate intestinal oxidative stress by regulating gut microbiota. Disclosure D.Dilimulati: None. M.Cai: None. Y.Zhang: None. S.Qu: None. M.Zhang: None.

Outcome of Gastric Bypass Surgery on Patients with Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is associated with obesity. The most effective method to achieve and maintain long-term weight loss is by the Roux-en-Y gastric bypass (RYGB). In this review, an overview about metabolic and PCOS-specific outcomes after RYGB in obese PCOS women is provided. The RYGB leads to an adequate excess weight loss and reduction in BMI in this patient population. Testosterone levels decline significantly at 6- and 12-months follow-up, as does the incidence of hirsutism and cycle irregularities. Data about fertility are scarce in this patient population. In conclusion, RYGB surgery seems to be an efficient treatment option for obese PCOS patients and leads to weight loss and improvements in metabolic parameters as well as in an improvement of PCOS-specific characteristics. However, larger prospective studies are warranted, which include all PCOS-specific outcome data in one patient population at the same time.

Leptin Inhibition Ameliorates Renal Mitochondrial Dysfunction And Associated Renal Injury In Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and polycystic ovaries. Renal injury, increased central adiposity and higher circulating levels of the adipokine leptin are common characteristics of PCOS. Leptin has direct renal fibrotic, hypertrophic, and albuminuric effects and can cause renal mitochondrial dysfunction and oxidative stress leading to chronic kidney disease development. Despite increased circulating leptin level in both lean and obese PCOS women, its role in PCOS-mediated renal damage remains unknown. In a well-characterized mouse model of PCOS, we aimed to test the hypothesis that hyperandrogenemia increases central adiposity leading to hyperleptinemia, which via leptin receptors induces intrarenal mitochondrial oxidative stress and dysfunction causing renal injury. Methods: Three-week-old peripubertal female mice were implanted with Silastic tubes filled with the non-aromatizable androgen dihydrotestosterone (DHT, 8 mg) or vehicle for 12 weeks. Eight weeks post-Silastic tubes implantation, the animals were treated with the leptin receptor antagonist (LepR-Ant) pegylated leptin (2 mg/kg, ip, 3x/week) for 4 weeks. Body weight, fat mass (EchoMRI), kidney weight (gravimetry), plasma leptin (ELISA), the glomerular filtration rate (GFR, transcutaneous fluorescence), as well as the renal injury markers urinary albumin to creatinine ratio (UACR, clinical chemistry analyzer), NGAL, and KIM1 (ELISA) were measured. Freshly isolated kidney mitochondria were used to measure mitochondrial reactive oxygen species (mtROS) by Amplex Red assay. Moreover, mitochondrial complex I and complex II-driven respiration and complex IV activity were assessed using Oroboros Fluorespirometer. Results: DHT significantly (p&lt;0.05) increased body weight (31.6 ± 2.3 vs. 23.6 ± 0.5 g), fat mass (3.5 ± 0.6 vs. 1.9 ± 0.4 g), kidney weight (365.6 ± 13.1 vs. 257.1 ± 3.7 mg), leptin (3.7-fold), UACR (1013.3 ± 56.4 vs. 658.9 ± 103.6 μg albumin/g creatinine), NGAL (6-fold), and KIM1 (3.7-fold). Moreover, PCOS mice had significantly (p&lt;0.05) lower GFR (1067.2 ± 59.9 vs. 1335.6 ± 60.3 uL/min/100g body weight), higher mtROS driven by complexes I (3.8 ± 0.8 vs. 2.0 ± 0.3 % electron leak) and III (8.0 ± 1.8 vs. 3.7 ± 0.9 % electron leak), as well as lower complexes I, II, and IV respiration (43-71%). The LepR-Ant had no effect on kidney weight or GFR; however, it abolished DHT-induced increases in body weight and fat mass. Excitingly, the LepR-Ant inhibited mtROS generation and completely restored complex I and II respiration, which was associated with a significant reduction in the urinary renal injury markers UACR, NGAL, and KIM-1 levels (40-60%, p&lt;0.05). Conclusion and significance: Our findings suggest that leptin via its receptor activation plays a significant role in the renal outcomes in PCOS by inducing mitochondrial dysfunction. Leptin receptor blockade could be a novel therapeutic approach to ameliorate renal injury in PCOS. Supported by NIH grants NIGMS P20GM121334 to KSE, LLYC, and DGR, NIGMS P20GM104357, NHLBI P01HL51971, and American Heart Association Predoctoral Fellowship 903804 (A.M.H.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of very low-calorie ketogenic diet with the Pronokal® method in obese women with polycystic ovary syndrome: a 16-week randomized controlled trial.

The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age. Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokal® method (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16. BMI decreased significantly in both groups and to a major extent in the experimental group (-13.7% vs -5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (-11.4% vs -2.9%), BIA-measured body fat (-24.0% vs -8.1%), and free testosterone (-30.4% vs -12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (-23% vs -13.2%, P > 0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P > 0.05) at the end of the study, respectively. In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokal® method was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction. To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese PCOS women.

Normoglycemic Obese and Non-Obese Women From North India With Polycystic Ovary Syndrome And Anti-Mullerian Hormone

Objective: Anti-Mullerian Hormone, often known as AMH, has been linked to a number of pathological disorders affecting the ovary, one of which is polycystic ovarian syndrome (PCOS). These patients' obesity, BMI, and hyperandrogenism are the triggers for a rise in the number of tiny antral follicles, which in turn affects the amount of AMH secreted. Method: AMH levels were compared with clinical, biochemical, and hormonal profiles in obese and non-obese PCOS women from Department of Community Medicine, TRR Institute of Medical Sciences, TRR Nagar, Inole, Hyderabad, Telangana, India, for the purpose of this study. Results: For this investigation, 54 cases of normoglycemic PCOS women were included. Among the patients, 62 (57.4%) had a BMI under 25 kg/m2, while 46 (42.6%) were obese. 48 patients (44.4%) had AMH 10 ng/ml. AMH 5ng/ml and obese PCOS individuals had significantly increased mean fasting insulin (P=0.01). In non-obese PCOS patients with AMH levels less than 5ng/ml, mean serum LDL-c was considerably higher (P=0.01), and mean serum LH was significantly higher in non-obese individuals with AMH 10ng/ml. Conclusion: Low AMH can be a significant marker for PCOS, and it should be routinely evaluated both for the diagnosis of PCOS and for the management of patients who have the condition. This is true regardless of the patient's BMI.

Detection The Polymorphism in exon- 6 for gene PPAR-ᵧ in Obese Polycystic Ovarian Syndrome Women

Peroxisome Proliferator Activated Receptors Gamma (PPAR-ᵞ) is a nuclear transcription factor, which Protein receptors for insulin and have a significant role in insulin resistance and Type 2 Diabetes mellitus in addition to the role of the gene encoded in the differentiation Adipocyte and the development of Adipose tissue. at present research has been detected substitution silent mutation C T in  the exon 6 of the gene PPAR-ᵧ in 111 women, including 73 obese women with Polycystic ovarian syndrome and 38 healthy women . in addition we determined certain biochemical variables  (Blood Sugar, HDL-C, Triglycerides) and find a body mass index (BMI) and compared between the two groups of women where the results showed significant difference value of BMI and the concentration of each of the (Blood Sugar, HDL-C, Triglycerides) and at (0.05 and 0.01) among Patient women and Healthy the results showed significant difference in mutant T allele frequency between them . The value in Obese PCOS women was (0.336) compared to the value at the healthy women (0:29) this indicates the a correlation between substitution silent mutation C T in exon 6 for PPAR-ᵧ and disease

Association of prolactin and insulin with obesity in women with polycystic ovarian syndrome

Introduction and Aim: Polycystic Ovarian Syndrome (PCOS) manifests with menstrual irregularities, infertility, galactorrhoea and hirsutism. Hormonal irregularities are found to be the pathogenesis behind PCOS. The study was aimed to evaluate whether obesity is associated with serum prolactin and insulin levels in PCOS women.    Materials and Methods: This case control study was conducted in a tertiary care hospital in Chennai. Control group included 30 apparently healthy women and cases included 30 PCOS patients, diagnosis based on Rotterdam criteria. The individuals were of 20-40 years of age in both the groups. The serum prolactin and insulin were analysed by ELISA. The obtained data were checked for normality of distribution and subjected to statistical analysis. Receiver Operating Characteristics (ROC) curve was done. Statistical analyses were performed using SPSS version 16.0. P less than 0.05 was considered statistically significant.   Results: The median and interquartile range (IQR) of serum insulin were 11.5 (1.8-70) and 5 (1.8-44) mIU/L in cases and controls respectively. The cut-off level of insulin was 7.0 mIU/L. The median and IQR of serum prolactin were 12.5 (4.5-53.0) and 12 (3.5-20) ng/mL in cases and controls respectively. BMI was positively correlated with age of the participants and prolactin.   Conclusion: PCOS is prevalent among obese reproductive individuals. Insulin was markedly elevated in PCOS individuals. Insulin resistance alters levels of luteinizing hormone and sex hormone binging globulins. Hyperprolactinemia is associated with anovulation or oligoovulation, galactorrhoea and hirsutism. In obese PCOS women, prolactin and insulin could be diagnostic markers of PCOS.

Serum uric acid/creatinine ratio and free androgen index are synergistically associated with increased risk of polycystic ovary syndrome in obese women

BackgroundFeatures of metabolic syndrome such as abdominal obesity, insulin resistance, hypertension and dyslipidemia are commonly encountered in polycystic ovary syndrome (PCOS). Recent evidence has suggested an association between high serum uric acid/creatinine (UA/Cr) ratio and metabolic syndrome however, no studies have investigated this association in PCOS. The current study was conducted to investigate the relationship between UA/Cr ratio and PCOS and to identify whether UA/Cr ratio and free androgen index (FAI) have an additive interaction for detection of PCOS risk in obese women.MethodsThis study enrolled 40 obese women with PCOS and 40 control women with regular menstrual cycles matched for age and body mass index (BMI). Anthropometric measurements, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids profile, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), total testosterone, free androgen index (FAI), UA/Cr ratio were assessed.ResultsSerum UA/Cr ratio was significantly higher in obese women with PCOS than in non-PCOS women. UA/Cr ratio was correlated with BMI, waist and neck circumferences, blood pressure, fasting insulin, HOMA-IR, lipids, LH/FSH, estradiol, DHEAS, total testosterone, FAI and SHBG. UA/Cr ratio and FAI were independent risk factors for PCOS in obese women however, the addictive interaction between UA/Cr ratio and FAI had a higher fold risk (OR: 4.3, 95% CI, 3.4–7.58) and a more significance (P = 0.002) for determination of PCOS.ConclusionSerum UA/Cr ratio combined with FAI can exert an additive or synergistic impact on prediction of PCOS in obese women.

Association between neutrophil-to-lymphocyte ratio and polycystic ovary syndrome: A PRISMA-compliant systematic review and meta-analysis.

Background:The neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a potential biomarker for assessing the systemic inflammatory response in polycystic ovary syndrome (PCOS). This meta-analysis is aimed at evaluating whether PCOS patients present with a higher NLR and whether obesity, metabolic, and hormonal indices have effects on the states.Methods:We performed a literature search on PubMed, Embase and Web of Science (last update: August 2, 2022). Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by applying random-effects models. Meta-regression analyses were used to explore the sources of heterogeneity and assess the relationship between NLR and several clinical parameters. Sensitivity analysis and publication bias were also assessed.Results:Thirteen studies involving 826 PCOS patients and 780 healthy controls were eligible for the present meta-analysis. Generally, NLR significantly increased in PCOS women versus healthy women (SMD = 0.81, 95% CI = 0.30–1.33, P = .002). NLR disparity was subsequently investigated in obese and non-obese cohorts. Obese PCOS women exhibited a higher NLR than obese controls (SMD = 0.56, 95% CI = 0.24–0.87, P = .001), and a similar difference was shown between non-obese PCOS and non-obese controls (SMD = 0.36, 95% CI = 0.02–0.71, P = .038). No significant NLR disparity was observed between obese versus non-obese PCOS women (SMD = 0.50, 95% CI = −0.37 to 1.38, P = .259). Meta-regression analysis revealed that NLR was significantly positively associated with fasting blood glucose (P = .006) and total cholesterol levels (P = .021), but not correlated with body mass index and other parameters in PCOS patients. Sensitivity analysis indicated that no individual study significantly affected the overall pooled result, and no publishing bias was observed.Conclusion:PCOS women typically present with an increased NLR. Such an increase is independent of obesity and may be associated with glycolipid metabolic disorders.

Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial.

ObjectivesCanagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy’s efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS).MethodsFifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated.ResultsCompared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively.ConclusionsIn overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy.Trial registration ClinicalTrials.gov, NCT04973891.

Prevalence of polycystic ovary syndrome in patients with type 2 diabetes: A systematic review and meta-analysis.

PurposeWith type 2 diabetes mellitus (T2DM) occurring at a younger age, a greater number of women with T2DM experience reproductive health problems. The prevalence of polycystic ovary syndrome (PCOS), a common reproductive disease associated with T2DM, remains unknown in women with T2DM. This systematic review and meta-analysis aimed to determine the prevalence of PCOS in women with T2DM.MethodsStata 15.1 was used to perform a meta-analysis on the prevalence of PCOS in patients with T2DM included in this study. Additionally, a narrative review of the effects of different diagnostic methods, obesity, state, and other factors on the prevalence of PCOS was conducted.ResultsMeta-analysis showed that the overall prevalence of PCOS in women with T2DM was approximately 21%. Subgroup analysis showed that the incidence of PCOS in female patients aged 25-45 years was higher than that in female patients aged < 25 years. The prevalence of PCOS in obese women was 14%, which was lower than that in normal weight women and normal weight or overweight or obese women. Women with T2DM in Oceania had the highest incidence of PCOS, followed by those in Europe and Asia; women with T2DM in North America had the lowest incidence. In terms of PCOS diagnostic standards, the prevalence of PCOS diagnosed by the National Institutes of Health was the lowest. The prevalence of PCOS diagnosed on the basis of clinical symptoms and biochemical characteristics was the highest, and the prevalence of PCOS diagnosed on the basis of medical records was 20%.ConclusionsPCOS is a common disease in female patients with T2DM. The prevalence of PCOS in women with T2DM at childbearing age was higher than that in adolescent females. Women with T2DM at childbearing age should pay attention to the screening and prevention of PCOS to avoid the hazards of PCOS to reproductive health.Systematic review registrationPROSPERO, identifier CRD42022318657.

Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT.

The majority of Polycystic ovary syndrome (PCOS) are overweight or obese with increased infertility and high risk of pregnancy complications. We aim to compare efficacy of metformin and exenatide on spontaneous pregnancy rate, overall pregnancy rate after assisted reproductive technology treatment (ART) and pregnancy outcomes in overweight or obese infertility PCOS. In this long-term follow-up study, 160 overweight or obese infertility Chinese PCOS were randomized to exenatide or metformin treatment for 12weeks. Afterward, all were treated with metformin alone until pregnancy confirmed and followed until delivery. If patients failed spontaneous pregnancy during the second 12weeks, ART could be offered until end of 64weeks. The primary outcome was spontaneous pregnancy rate. At week 24, 29.2% of women in exenatide group conceived spontaneously while 14.7% in metformin group (p = 0.03). At week 64, total pregnancy rates were 79.2% in exenatide group and 76% in metformin group without significant difference (p = 0.65). Between two groups, there was no significant difference of pregnancy outcomes (p > 0.05). A stepwise logistic regression showed that spontaneous pregnancy was positively associated with body weight reduction and HOMA-IR improvement in either group. In overweight or obese infertility Chinese PCOS, 12weeks pregestational exenatide treatment resulted in more spontaneous pregnancy likely due to greater weight reduction and improvement of insulin resistance compared with metformin treatment without obvious benefit on overall pregnancy rate after ART or pregnancy outcomes of successful conceived women. This clinical trial was registered at Chinese Clinical Trials Registry (ChiCTR-IIR-16008084) on 13/3/2016.

Therapy of obesity in women with PCOS using GLP-1 analogues - benefits and limitations [Terapia otyłości u kobiet z PCOS przy zastosowaniu analogów GLP-1 - korzyści i ograniczenia].

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder among women of reproductive age. The incidence ranges from approx. 6% to 20%. PCOS is characterized by a spectrum of symptoms and clinical features that includes ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and ultrasound evidence of morphologically polycystic ovaries. Obesity is present in 40-70% of patients with the syndrome. Adiposity is involved in exacerbating the negative effects of insulin resistance, hyperinsulinaemia, and hyperandrogenaemia in the course of PCOS. Therefore, it is essential to maintain normal weight or effectively treat overweight/obesity in patients suffering from this endocrinopathy. Apart from diet and lifestyle interventions, an appropriate pharmacological or surgical treatment should be selected for the individual patient. Evidence-based data have unequivocally proven the validity of the use of glucagon-like peptide 1 (GLP-1) analogues in the treatment of overweight/obese patients with PCOS. The result of the GLP-1 therapy is not only a reduction of body weight but also an improvement in insulin resistance and a decrease in hyperandrogenaemia. It also seems that this treatment method increases spontaneous and in-vitro pregnancy rates. Therefore, the GLP-1 treatment of obese PCOS women is a new therapeutic opportunity not only for weight loss but also for a wide range of benefits. This review summarizes and discusses findings regarding obesity and its relation to hyperandrogenism and insulin resistance in PCOS, with special attention paid to the pharmacological treatment of adiposity with GLP-1 analogues.