Lean Polycystic Ovary Syndrome Research Articles

The impact of polycystic ovary syndrome and body mass index on the absorption of recombinant human follicle stimulating hormone.

Women with polycystic ovary syndrome (PCOS) have an increased ovarian responsiveness to exogenous recombinant follicle stimulating hormone (rFSH) but also have high rates of obesity, which is known to affect serum FSH concentrations following exogenous injection. The purpose of this study was to compare rFSH absorption and ovarian response between lean and overweight/obese PCOS subjects and normo-ovulatory controls. Fourteen women with PCOS aged 18-42years old with a BMI of 18.5-24.9kg/m2 (normal) or 25.0-40.0kg/m2 (overweight/obese) and eleven normo-ovulatory controls matched by age and BMI were included. After downregulation with oral contraceptives, participants were administered a single subcutaneous injection of 225IU rFSH and underwent serial blood draws over 72h. Lean PCOS subjects exhibited a significantly higher area under the curve (AUC) of baseline-corrected serum FSH over 72h when compared with overweight/obese PCOS subjects (183.3 vs 139.8IU*h/L, p= 0.0002), and lean, normo-ovulatory women had a significantly higher AUC FSH when compared with overweight/obese, normo-ovulatory women (193.3 vs 93.8IU*h/L, p< 0.0001). Within overweight/obese subjects, those with PCOS had a significantly higher AUC FSH compared with normo-ovulatory controls (p= 0.0002). Lean PCOS subjects similarly had the highest AUC of baseline-corrected estradiol (6095pgh/mL), compared with lean normo-ovulatory subjects (1931pgh/mL, p< 0.0001) and overweight/obese PCOS subjects (2337pgh/mL, p< 0.0001). Lean PCOS subjects exhibited significantly higher baseline-corrected FSH and estradiol levels following rFSH injection compared with overweight/obese PCOS subjects with similar ovarian reserve markers. Amongst overweight/obese subjects, those with PCOS had significantly higher FSH and E2 levels when compared with normo-ovulatory controls.

Metabolomic biomarkers of polycystic ovary syndrome related-obesity: a review of the literature

Abstract Background and objectives: Polycystic ovary syndrome (PCOS) displays a phenotype-dependent cardio-metabolic risk. By performing a systematic search of the literature, we aimed to summarize metabolomic signatures associated with obesity in PCOS women. Data sources and study eligibility criteria: We conducted a comprehensive search including: Embase, PubMed, and Web of Science until 31st of May 2019. We used the terms: metabolomics and polycystic ovary syndrome. We excluded the following papers: animal studies, studies that included only lean PCOS women, reviews, meta-analyses, results of interventional studies, those that did not apply metabolomic techniques. Results: The lipid signature in obese women with PCOS showed increased levels of free fatty acids (carnitine, adipic acid, linoleic acid, oleic acid) and lower levels of lysophosphatidylcholines and glycerolphosphocholine compared with non-obese PCOS women. Regarding carbohydrate metabolism, a decrease in citric and lactic acid levels characterized obese PCOS women. Decreased lactic acid in obese PCOS women suggests augmented insulin stimulated glucose muscle use in lean, but not in obese women. Considering amino acid metabolomic markers, valine, glycine, serine, threonine, isoleucine and lysine were higher in obese PCOS women. Patients with visceral obesity presented a diminished uptake of essential amino acids, BCAA, leucine and serine in the skeletal muscle. α-ketoglutarate was significantly higher in obese women with PCOS in comparison with lean women with PCOS, distinguishing these 2 subgroups of PCOS with high ‘predictive accuracy’. Limitations: Overall, a small number of studies have focused on the impact of obesity on the metabolic fingerprints of PCOS women. There is need for properly controlled, high-quality studies. Conclusions: There is compelling evidence of significant alterations in carbohydrate, lipid, and amino acid metabolism in women with PCOS and obesity. Metabolomics may identify new metabolic pathways involved in PCOS and improve our understanding of the complex relation between PCOS and obesity in order to personalize PCOS therapy.

Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean women with polycystic ovary syndrome: insights from a large Caucasian cohort.

Polycystic ovary syndrome (PCOS), considered a lifelong condition, manifests mainly as a cluster of hyperandrogenic symptoms during the early reproductive years, with the affected woman gradually developing an adverse cardiometabolic profile over the years. However, some data point to the possibility of differences in the evolution of PCOS according to a woman's weight. The aim of the present study was to evaluate the metabolic and hormonal profiles of women with PCOS over time. A total of 763 lean women with PCOS (BMI 20-25kg/m2) and 376 controls were included. The study group was further divided into three age groups representing women post-adolescence, of reproductive age, and of late reproductive age. All subjects were assessed clinically, biochemically, and hormonally. Waist circumference, lipids, androgens, and insulin resistance index (homeostasis model assessment of IR index (HOMA-IR)) were significantly higher in the PCOS group compared with controls. Age subgroup analysis showed a progressive decrease of HOMA-IR and waist circumference, and lipid levels were comparable between PCOS and controls in all age groups. Androgens remained significantly higher in PCOS, but they gradually decreased through time. A significant negative association of age with waist circumference, androgens, insulin, and HOMA-IR was revealed. Univariate and multivariate regression analysis disclosed a strong correlation of HOMA-IR with age (p = 0.014, β - 0.19, SE coefficient 0.008) as a single parameter or in combination with total cholesterol (TC) (p < 0.001, age: β - 0.023, SE 0.10; TC: β 0.084, SE 0.027). Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean PCOS women. We hypothesize that if these women do not gain weight with the passage of time, there is a high probability that their cardiometabolic risk will be attenuated.

The Use of SenseWear Armband for Assessment of Daily Energy Expenditure and the Relation to Body Fat Distribution and Nutritional Intake in Lean Women with Polycystic Ovary Syndrome.

Objective To evaluate nutritional intake, energy expenditure, and segmental body composition in lean women with polycystic ovary syndrome (PCOS) and compare them with age- and body mass index- (BMI-) matched control women. Methods 32 nonobese patients with PCOS and 31 age- and BMI-matched healthy women were included in the study. Energy expenditure and physical activity level were assessed by metabolic Holter equipment (SenseWear Armband, SWA) which was never previously used in lean PCOS population. Food intake is recorded with 24 hours of food record. Segmental body composition analysis was assessed by bioelectrical impedance analyses (BIA). Results Mean BMI was 22.64 ± 3.64 and 21.55 ± 2.77 kg/m2 (p=0.185) in PCOS and control groups, respectively. Mean age was 22.03 ± 4.21 and 21.71 ± 2.67 year (p=0.720), respectively. No significant differences were found in total energy intake and percentage of carbohydrates, fats, and other micronutrients (p > 0.05). Energy percentage of proteins (%12.73 ± 1.98, p=0.008) was statistically lower in subjects versus the control group. The measurements of physical activity duration (PAD) (1.40 ± 0.87/2.18 ± 0.99 hours, p=0.002), active energy expenditure (372.35 ± 198.32/494.10 ± 186.50 kcal, p=0.018), and step counting (9370.03 ± 3587.49/11730.90 ± 3564.31 steps, p=0.013) measurement of the PCOS group were lower than the control group, respectively. Conclusions New diagnosed women with PCOS had similar distribution and quantity of body fat parameters and nutritional status when compared to healthy women. Control subjects were found more active in energy expenditure.

Ovarian 25OH-vitamin D production in young women affected by polycystic ovary syndrome.

Vitamin D is involved in the regulatory mechanisms of ovarian function and is frequently low in PCOS patients. Since obesity and hyperinsulinemic state negatively influenced vitamin D levels, therefore, we evaluated the production of vitamin D at the ovarian level only in lean and normoinsulinemic PCOS subjects. Basal, GnRH analogue-induced ovarian production of 25OH-vitamin D (VitD) and a direct sampling at ovarian vein level were investigated. Basal and GnRH analogue-induced hormone levels were evaluated at peripheral level in 45 subjects, aged 18-39years, and in 22 healthy women with age- and BMI-matched as controls. In 12 PCOS patients, undergoing laparoscopy, a venous sampling at both peripheral and ovarian level was further done. All subjects presented low VitD levels, appropriate to the season and with no difference between PCOS and control subjects. GnRH analogue significantly stimulated plasma LH, FSH, 17-OHP and estradiol secretion (p from < 0.05 to < 0.001 vs basal levels), whereas no effect was observed on both serum AMH and VitD concentrations in all groups. A significant difference (p < 0.006), between peripheral and ovarian veins, was observed in both AMH and estradiol levels in PCOS subjects, while no gradient of VitD was detected. All patients presented with low VitD levels. The absence of any VitD variation, both at basal and after GnRH analogue administration, or at peripheral-ovarian vein gradient, suggests no pituitary-ovarian axis involvement in VitD production or its direct ovarian production in lean and normoinsulinemic PCOS subjects.

IN-UTERO ANDROGEN EXPOSURE CHANGES NEONATAL OVARIAN GENE EXPRESSION AND MITOCHONDRIA IN A LEAN PCOS MODEL

Polycystic ovary syndrome (PCOS) affects up to 10% of women worldwide, has a strong hereditary pattern with a heterogeneous phenotype. While no candidate genes have been found, a shared disease predisposing environment, such as intrauterine hyperandrogenemia, may explain an epigenetic inheritance pattern. A lean PCOS mouse model, eliminating the obesity confounder, with maternal androgen administration prenatally, provides an opportunity to study the effect of androgens on fetal programming.

Low‐Dose Dihydrotestosterone Lowers Lipogenic Master Regulator in Liver and Adipose Tissue from Female Mice

Polycystic Ovarian Syndrome (PCOS) is the leading cause of infertility among women caused by high androgen levels and affects 1 in 10 women. Due to the premature use of hormonal birth control, a large population of women are unaware they have symptoms of PCOS. Non‐Alcoholic Fatty Liver Disease is a continuum of inflammation that limits the livers ability to function properly.Lean hyperandrogenic (HA) women who are diagnosed with PCOS have been associated to also have insulin resistance (IR) and Non‐Alcoholic Fatty Liver Disease (NAFLD). We hypothesized that low dose (dihydrotestosterone) DHT would interrupt hepatic lipid metabolism leading to NAFLD. Proving that the HA and HFD induced insulin resistance pathways are connected would be beneficial for the lives of women with Type 2 Diabetes and PCOS, as it could aid in early screening and detection for NAFLD.We used a low dose DHT animal model to induce the PCOS symptoms onto the mice. Protein concentration assay was run on the liver, adipose, and skeletal muscle tissues using bicinchoninic acid (BCA) protein assay. Proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and transferred to nitrocellulose membranes to be prepared for Western blot analysis. They were blocked then incubated with primary antibodies (SREBP1, SREBP2, p‐ACC, ACC, and FAS; 1:1000 dilution), using GAPDH as a loading control. After incubation with secondary antibodies (goat anti‐mouse IgG; 1:5000 dilution), enhanced chemiluminescence was used for detection of proteins. Densities were quantified using myImageAnalysis software and analyzed by two‐tailed t‐tests with Prism software.The increased hepatic lipid content of DHT mice signifies that the low dose DHT causes NAFLD. Low dose DHT mice displayed decreased inactive and active forms of cytosolic SREBP1c and increased levels of FAS. Inactive and active forms of SREBP2 and p‐ACC levels were the same in control and DHT mice. Low dose DHT lowered the active form of SREBP1c but not the inactive form in WAT compared to controls. In comparison to the controls, p‐ACC was decreased in low dose DHT mice. FAS and the inactive and active form of SREBP2 were unaltered in low dose DHT mice compared to controls. ChREBP protein levels were not readily detected and unchanged in WAT tissue of low dose DHT mice compared to controls. ASCVL1 (FATP2) protein expression was increased in WAT of low dose DHT mice. PPARy was unchanged in WAT of low dose DHT mice compared to controls. FXR protein levels were trending towards being increased but were not significantly different in WAT of low dose DHT mice compared to controls. Visfatin protein levels were not readily detected or altered in WAT tissue of low dose DHT mice compared to controls.Overall, the findings suggest that low‐dose DHT is causing the translocation of SREBP‐1 from the cytosol into the nucleus leading to increased lipogenic gene expression. Low‐dose DHT does not affect overall lipogenic gene expression in skeletal muscle of female mice. Future studies may focus on nuclear extraction to isolate key nuclear proteins (SREBP‐1, SREBP‐2) in order to see whether they are translocated to the nucleus.Support or Funding InformationFunded by the APS STRIDE Fellowship and Howard University Faculty Start up funds. Preliminary data collection and analysis completed by Tina Seidu, Patrick McWhorter, Rabita Alamgir, and Dilip Bogle.Low‐dose DHT (a mouse model of lean PCOS) caused NAFLD.Figure 1

Serum betatrophin levels are significantly increased in obese patients compared to lean patients regardless to the presence of PCOS

Betatrophin, which regulates glucose metabolism, is primarily expressed in liver and fat tissue. We aimed to investigate betatrophin levels in patients with polycystic ovary syndrome (PCOS) that is the most common endocrine pathology in women of reproductive age. A total of 69 women were included in this prospective study: 35 patients with PCOS (18 obese and 17 lean) and 34 healthy controls (17 obese and 17 lean). Patients who met the criteria were compared regarding betatrophin levels and other hormonal values. Serum betatrophin level did not differ between obese PCOS patients and obese controls, and lean PCOS patients and lean controls; while significantly increased in obese PCOS patients and controls compared to lean PCOS patients and controls. Total testosterone and androstenedione were significantly higher in patients with PCOS than in controls both in the obese and lean groups, while sex hormone–binding globulin was significantly lower in patients with PCOS than in controls both in the obese and lean groups. However, remaining hormone values were similar between groups. Betatrophin level was significantly increased in obese patients compared to lean patients independent to the presence of PCOS.

Study of Serum Chemerin in Patients of Polycystic Ovarian Syndrome and its Relation to Insulin Resistance

Abstract Background study of chemerin level in polycystic ovarian syndrome (PCO) patients and its relation to insulin resistance (IR). Upon chemerin on adipose tissue and glucose metabolism, serum chemerin has been recently studied in (PCO) women Aim We aimed to study the level of serum chemerin in PCO patients and its relation to insulin resistance. Methods The current study included 45 subjects with PCO syndrome and 45 healthy subjects as a control group. PCO subjects were divided into 27 obese PCO and 18 lean PCO. Control women were divided into 25 obese women and 20 lean women. Measurement of serum chemerin levels, fasting blood glucose (FBG),fasting insulin (FIN), total testosterone and pelvic ultrasonography Results Serum chemerin was significantly higher in the obese PCOS group (99.65 ± 13.72 ng/mL) compared with lean PCOS (87.99 ± 5,64 ng/mL) and the obese (76.82 ± 2.39 ng/mL) and non-obese (69.19 ± 8.40 ng/mL) control groups. In PCOS women, serum chemerin levels were positively correlated with Body mass index (BMI) (r = 0.835, P &amp;lt; 0.001), Fasting blood glucose (FBG) (r = 0.493, P &amp;lt; 0.005), Fasting insulin (FIN) (r = 0.913, P &amp;lt; 0.001), Homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.9181, P &amp;lt; 0.001). Conclusion There is an increase in serum chemerin level in PCOS patients with even more significant increase in patients with obese PCOS.

Prenatal androgen induced lean PCOS impairs mitochondria and mRNA profiles in oocytes.

Polycystic ovary syndrome (PCOS) is the most common ovulatory defect in women. Although most PCOS patients are obese, a subset of PCOS women are lean but show similar risks for adverse fertility outcomes. A lean PCOS mouse model was created using prenatal androgen administration. This developmentally programmed mouse model was used for this study. Our objective was to investigate if mitochondrial structure and functions were compromised in oocytes obtained from lean PCOS mouse. The lean PCOS mouse model was validated by performing glucose tolerance test, HbA1c levels, body weight and estrous cycle analyses. Oocytes were isolated and were used to investigate inner mitochondrial membrane potential, oxidative stress, lipid peroxidation, ATP production, mtDNA copy number, transcript abundance and electron microscopy. Our results demonstrate that lean PCOS mice have similar weight to that of the controls but exhibit glucose intolerance and hyperinsulinemia along with dysregulated estrus cycle. Analysis of their oocytes show impaired inner mitochondrial membrane function, elevated reactive oxygen species (ROS) and increased RNA transcript abundance. Electron microscopy of the oocytes showed impaired mitochondrial ultrastructure. In conclusion, the lean PCOS mouse model shows a decreased oocyte quality related to impaired mitochondrial ultrastructure and function.

Prevalence of type 2 diabetes mellitus compared between lean and overweight/obese patients with polycystic ovarian syndrome: a 5-year follow-up study.

To investigate the prevalence of type 2 diabetes mellitus (T2DM) at the 5-year follow-up after polycystic ovarian syndrome (PCOS) diagnosis compared between lean and overweight/obese groups. This retrospective cohort study included 400 prediabetes PCOS women who attended our clinic. Participants were divided into either the lean group (body mass index [BMI]: < 23kg/m2) or the overweight/obese group (BMI: ≥ 23kg/m2). Patient demographic, clinical characteristics, metabolic profiles, and laboratory values were collected and compared between groups at baseline and during follow-up for 5years. At the end of the follow-up, overweight/obese group had a higher risk for developing T2DM than lean group (11.5% vs. 0.5%, p < 0.001). Lean group had a lower incidence of hypertension (3% vs. 38.5%, p < 0.001) and dyslipidemia (35% vs. 53.5%, p < 0.001) than overweight/obese group. The factors found to be independently associated with increased risk for developing T2DM were BMI ≥ 23kg/m2 (odds ratio [OR]: 1.075, p = 0.047), non-use of oral combined contraceptive pills (OR: 0.312, p = 0.028), and impaired fasting glucose at baseline (OR: 38.167, p < 0.001). Overweight/obese PCOS patients were found to be at significantly higher risk for developing T2DM than lean PCOS patients. Higher BMI, IFG at baseline, and non-use of oral contraceptive pills found to be independent predictors of T2DM in PCOS.

Meta-analysis of gene expression profiles of lean and obese PCOS to identify differentially regulated pathways and risk of comorbidities

Polycystic ovary syndrome (PCOS) is a complex multigenic disorder and women with PCOS suffer from several comorbidities. Although, obesity is a known risk factor for PCOS, the incidence of lean women with PCOS is on the rise. A systematic and comparative study on lean and obese PCOS with respect to genes, pathways and comorbidity analysis has not been attempted so far. Analysis of differentially expressed genes (DEGs) across tissue types for lean and obese PCOS revealed that the majority of them were downregulated for lean and obese PCOS. Ovarian and endometrial tissues shared several commonly dysregulated genes, suggesting shared PCOS pathophysiology mechanisms exist across tissues. Several pathways for cellular homeostasis, such as inflammation and immune response, insulin signaling, steroidogenesis, hormonal and metabolic signaling, regulation of gonadotrophic hormone secretion, cell structure and signaling that are known to be affected in PCOS were found to be enriched in our gene expression analysis of lean and obese PCOS. The gene-disease network is denser for obese PCOS with a higher comorbidity score as compared to lean PCOS.

Significance of Body Mass Index in the Classification of PCOS: A Comparative Study in Northeast India

ABSTRACTAimTo compare the clinical and biochemical characteristics of obese and lean women with polycystic ovary syndrome (PCOS). To confirm the significance of body mass index (BMI) in classifying PCOS.Materials and methodsThis was a comparative cross-sectional study done at Assam Medical College Hospital, Dibrugarh, Assam, in 1 year. Women who attended the hospital diagnosed to have PCOS based on Rotterdam's criteria were divided into lean and obese with BMI cut-off of 23. Clinical, anthropometric, and biochemical characteristics of both were compared. Body fat percentage was calculated using Harpenden skinfold calipers, and based on it, the lean group was found to have a normal weight, and obese subgroup with body fat percentage more than the cut-off.ResultThere was a significant difference in age, hirsutism score, and family history of diabetes and PCOS between the groups. The systolic blood pressure, serum cholesterol, and serum low-density lipoprotein (S.LDL) were statistically higher in the obese group. The normal weight obese group had features of the lean group, except for hyperandrogenism.ConclusionThe lean and obese PCOS are two discrete groups. Obese patients have a more androgenic and atherogenic lipid profile, but both groups should be screened. Body mass index is the easily available method, but it has a chance of missing out on the normal weight obese PCOS.Clinical significanceFollow-up is needed in both the groups, and the normal weight obese group behaves as the lean PCOS group; hence, BMI can be continued to be used as the differentiating factor.How to cite this articlePillai SS, Phukan PK, Dihingia P. Significance of Body Mass Index in the Classification of PCOS: A Comparative Study in Northeast India. J South Asian Feder Obst Gynae 2020;12(3):145–149.

Relationship of subclinical hypothyroidism and obesity in polycystic ovarian syndrome patients.

Objectives:To determine the prevalence of obesity and its relationship with subclinical hypothyroidism in women with polycystic ovarian syndrome (PCOS). To compare the clinico-biochemical parameters of obese and lean PCOS patients.Materials and Methods:A total of 287 women with PCOS were included in this study after consent. The demographic, anthropometry, clinical, and hormonal (thyroid-stimulating hormone [TSH] and total testosterone) parameters were recorded along with pelvic ultrasonography (USG) for all PCOS subjects. They were divided into lean (body mass index [BMI] between 18.5 and 22.9) and overweight (BMI ≥23), and the number of subclinical hypothyroid patients were calculated in each group. The clinico-biochemical parameters of both groups were compared.Results:The majority (61%) of our patients were overweight. There was no significant difference in the prevalence of subclinical hypothyroidism between overweight and lean PCOS patients. The obese PCOS patients were older than lean PCOS patients, and they had higher serum testosterone with elevated systolic and diastolic blood pressure (BP).Conclusion:The majority of our patients were found to be overweight and there was no association between obesity and subclinical hypothyroidism among PCOS patients.

Prevalence of hyperandrogenism in Iraqi women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a mainly common endocrine disorder. Hyperandrogenism is the major standard in the diagnosisof PCOS development.Eighty women diagnosed with PCOS and twenty healthy women(aged 20-40 years)were enrolled in this study which was conducted at the infertility clinic of Kamal AL-Samaraay Hospital/ Baghdad. The diagnosis of PCOS was made according to the Rotterdam criteria. Body mass index (BMI, Kg/m2)was calculated by a specific formula. History of menstrual irregularity, hirsutism, acne, and alopecia was taken. Hormone levels in serum, namely luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were measured in all patients and control subjects.There was a statistically significant difference (P &lt;0.05) in the BMI between the PCOS and control women.Also, the prevalence of overweight and obesity was much higher in PCOS women than in their matching control. The serum levels of LH, FSH, and testosterone were significantly different (P &lt;0.05) in PCOS as compared to healthy women. Clinical hyperandrogenism (hirsutism and alopecia) were present in most of PCOS women, while acne wasa less useful clinical sign of hyperandrogenism.Inaddition, the prevalence of hirsutism and alopecia was increased in obese when compared with overweight and lean PCOS women.

Effects of Metformin Treatment on Soluble Leptin Receptor Levels in Women with Polycystic Ovary Syndrome

The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated. This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, China. Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months. According to body mass index (BMI), the patients were divided into two groups: lean PCOS group (BMI <23 kg/m2, n=34) and overweight or obese PCOS group (BMI ≥23 kg/m2, n=21). Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), insulin and sOB-R levels were determined. Thirty-one BMI-matched ovulatory women served as controls. The results showed: (1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), androgen levels and hirsutism scores were higher, and sOB-R levels were lower in PCOS groups than in control group. A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group. There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls. However, sOB-R level was significantly lower in lean PCOS women than in controls. (2) There was no correlation between sOB-R level and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores in PCOS patients, but there was a significant negative correlation between sOB-R and HOMA-IR. (3) After treatment with metformin for 6 months, serum insulin levels decreased, and sOB-R levels increased significantly (P<0.01). It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance. It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.

Efficacy of combination therapy of inositols, antioxidants and vitamins in obese and non-obese women with polycystic ovary syndrome: an observational study

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of both developed and developing countries. It is associated with insulin resistance, hyperinsulinemia, hyperandrogenism, oxidative stress and various long-term complications. The present study was undertaken to evaluate the efficacy and safety of the supplementation (Trazer F ForteTM-CORONA Remedies Pvt. Ltd.) providing combination of insulin sensitising agents (myo-inositol, D-chiro-inositol and chromium picolinate), antioxidants (N-acetylcysteine and lycopene) and vitamins (vitamin D, biotin and folic acid) in women with PCOS. After 12 weeks of supplementation, a significant improvement was observed in menstrual cyclicity, acne and hirsutism in both obese and lean PCOS patients. A significant reduction was observed in body weight and BMI of obese subjects. However, both parameters remain unchanged in lean subjects. We suggest that combination therapy of insulin sensitising agents, antioxidants and vitamins may be a fruitful approach for the management of PCOS.Impact statementWhat is already known on this subject? Monotherapy of insulin sensitising agents, antioxidants and vitamins is beneficial in the treatment of PCOS.What do the results of this study add? Combined use of insulin sensitising agents (myo-inositol, D-chiro-inositol and chromium picolinate), antioxidants (N-acetylcysteine and lycopene), and vitamins (vitamin D, biotin and folic acid) is safe and effective in obese and non-obese women with PCOS.What are the implications of these findings for clinical practice and/or further research? Since PCOS is a multifactorial and a complex endocrine disorder, combination therapy can be used for the comprehensive management of PCOS.

RS1799817 in INSR associates with susceptibility to polycystic ovary syndrome.

Insulin and its receptor (INSR) have been implicated in the etiology of the polycystic ovarian syndrome (PCOS). Here, we investigate the association between INSR rs1799817 polymorphism and PCOS in Saudi Arabian women. Study group included 126 PCOS women and 118 normo-ovulatory matched controls. The demographic data was recorded, and the plasma levels of glucose, lipids, leptin, E2, LH, FSH, T, SHBG, and insulin were determined. The genotypic and allele frequencies of rs1799817 were evaluated in both PCOS and control group. Polymerase chain reaction (PCR) was used to amplify Exon 17 of the INSR gene, and the amplified products were analyzed by direct sequencing. A single-nucleotide polymorphism (C to T) was found at locus 10923 (His1058) of rs1799817. In the PCOS group, the mutant allele T occurs at a significantly higher frequency (0.306) compared to the control group (0.174) (p<0.001). It shows a dominant effect and elevates the relative risk of PCOS even in the heterozygotes (RR=2.82). After stratification of the participants by body mass index, the frequency of T allele was significantly higher in the lean patients with PCOS compared to the lean control. The obese PCOS also had a higher frequency than the obese control, but the difference was not statistically significant. Several parameter values were affected by the INSR genotype, particularly W/H ratio, lipid, insulin and glucose levels and insulin resistance in PCOS patients. The INSR gene polymorphism rs1799817 is a susceptibility locus associated with PCOS in Saudis and associated metabolic and hormonal changes, particularly, in the lean PCOS females.

Relation of NT-probnp levels and cardiovascular disease risk factors in lean women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. N-terminal fragment of brain natriuretic peptide (Nt-probnp) is used as a diagnostic and prognostic marker for CVD. The aim of this study was to evaluate whether Nt-probnp is increased in lean PCOS patients. A total of 110 lean (BMI < 25 kg/m2) PCOS patients and 80 age and BMI matched healthy lean controls were included in this study. Serum Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), Matsuda insulin sensitivity index (ISI), Nt-probnp, C-reactive protein (CRP), androgen and lipid levels were measured. Serum Nt-probnp levels were significantly higher in the PCOS group. Hyperandrogenic PCOS patients had higher Nt-probnp levels. There were significant correlations between serum Nt-probnp and total testosterone, total cholesterol, HOMA and Matsuda levels. Linear regression analysis showed that Matsuda ISI and fasting insulin levels significantly affected the Nt-probnp levels (R2 of the model = 0.763; p<.0001).IMPACT STATEMENTWhat is already known on this subject? Many risk factors for cardiovascular disease (CVD) including insulin resistance, dyslipidaemia, hypertension and hyperandrogenism may be found in young women with polycystic ovary syndrome (PCOS), although evidence for CVD in lean women with PCOS is limited. N-terminal fragment of brain natriuretic peptide (NT-probnp) is a high predictive marker regarding of CVD, especially in patients without overt CVD. There have been contradictory results regarding Nt-probnp levels in PCOS patients and there have not been any effective studies regarding the relation between CVD risk factors and Nt-probnp levels for lean PCOS patients.What the results of this study add? This study found increased Nt-probnp levels in lean PCOS patients, which may indicate a positive correlation with risk for CVD. Strong relations were also found between Nt-probnp levels and increased insulin resistance, dyslipidaemia, decreased insulin sensitivity and hyperandrogenism. Lean PCOS patients have increased risk factors for CVD, and these risk factors are correlated with Nt-probnp levels. Nt-probnp is more affected by increased fasting insulin and decreased insulin sensitivity.What the implications are of these findings for clinical practice and/or further research? Lean PCOS patients should be evaluated for CVD. Further prospective controlled studies are needed in order to predict the long-term risk of developing CVD in lean PCOS patients.

787-P: Prevalence of Metabolic Syndrome in Indian Women with Polycystic Ovarian Syndrome (PCOS) and the Correlation of Dietary Nutrient Composition and Physical Activity on Components of the PCOS—A Pilot Study

Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine problem in women of reproductive age group and has been linked to infertility, insulin resistance, obesity, hypertension, dyslipidemia and diabetes. Objective: In this pilot study we seek to study the impact of meal time habits and physical activity on the prevalence of metabolic syndrome(Met Syn) in Indian women with PCOS. Methods: 36 women (age: 28±1.4 years, BMI: 31.7 ± 0.84 kg/m2) with a diagnosis of PCOS (NIH criteria) participated in a detailed questionnaire with dietary habits and physical activity. Anthropometric measurements and fasting blood glucose, lipid profile, HbA1c were obtained in all subjects. Results: In this group of women with PCOS, the prevalence of Met Syn was 43% and only 2 women had lean PCOS (BMI&amp;lt;25kg/m2). The prevalence of diabetes and impaired fasting glucose was 9% and 30% respectively. Of the components of Met Syn, all subjects had low HDL and high waist circumference, 25% had hypertension. Dietary history revealed that majority (84%) had a daily breakfast and only 16% skipped the breakfast. However, there was no difference in prevalence of metabolic abnormalities between those who had versus those who did not have breakfast. On the other hand women who were more physically active (&amp;gt;1 hour of physical activity/day) had lower BMI, systolic blood pressure (125± 3.4 vs. 112± 5.4, p&amp;lt;0.05 mm of Hg), a lower triglyceride level and a lower prevalence of Met Syn. Conclusions: The prevalence of Met Syn was very high in our pilot group of relatively young Indian women with PCOS. Women with lower physical activity had a higher prevalence of metabolic abnormalities suggesting the significance of increasing physical activity to prevent Met Syn in PCOS. Larger studies are indicated to develop dietary and physical activity guidelines specific to this "ethnic" high risk Indian group to prevent future diabetes. Disclosure R. Mehta: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc. H. Varma: None.