Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome.

PubMed

Chen, Chin-I; Hsu, Ming-I; Lin, Shyh-Hsiang; Chang, Yuan-Chin I; Hsu, Chun-Sen; Tzeng, Chii-Ruey

2015-04-01

The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). This was a retrospective study. Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Endothelial function in young women with polycystic ovary syndrome (PCOS): Implications of body mass index (BMI) and insulin resistance.

PubMed

El-Kannishy, Ghada; Kamal, Shaheer; Mousa, Amany; Saleh, Omayma; Badrawy, Adel El; Farahaty, Reham El; Shokeir, Tarek

2010-01-01

Evidence regarding endothelial function in both obese and nonobese women with PCOS is contradictory. It is unknown whether obese women with PCOS carry an increased risk related to body mass index (BMI). To identify endothelial function and investigate its relationship to body mass index and insulin resistance in young women with PCOS. Twenty-two obese women with PCOS (BMI 35.2 ± 3.2) as well as fourteen lean women (BMI 22.8 ± 2.1)with PCOS were included in the study. Fasting serum insulin, blood glucose were estimated and HOMA and Quicki index were calculated. All patients were subjected to ultrasound recording of brachial artery diameter at rest and after reactive hyperemia (FMD) for assessment of endothelial function. Ten age matched healthy females with normal BMI were chosen as a control group. There were higher basal insulin levels with lower Quicki index and higher HOMA index in women with PCOS than normal group, but the differences were significant only between obese PCOS subgroup and control. On the other hand, FMD was significantly and equally decreased in both groups of women with PCOS, compared with control subjects (3.7 ± 3.2% in the nonobese subgroup and 3.5 ± 2.8% in the obese one vs. 10.6 ± 4.1% in control subjects, P, 0.001). FMD was not correlated with BMI nor insulin resistance indices. Endothelial dysfunction is already present in young women with PCOS. In this patient group, it cannot be attributed to insulin resistance or obesity. © 2010 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

PubMed

Ollila, M-M E; West, S; Keinänen-Kiukaanniemi, S; Jokelainen, J; Auvinen, J; Puukka, K; Ruokonen, A; Järvelin, M-R; Tapanainen, J S; Franks, S; Piltonen, T T; Morin-Papunen, L C

2017-02-01

What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m 2 ) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring

Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus—a prospective, population-based cohort study

PubMed Central

Ollila, M.-M.E.; West, S.; Keinänen-Kiukaanniemi, S.; Jokelainen, J.; Auvinen, J.; Puukka, K.; Ruokonen, A.; Järvelin, M.-R.; Tapanainen, J.S.; Franks, S.; Piltonen, T.T.; Morin-Papunen, L.C.

2017-01-01

STUDY QUESTION What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28–4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years

Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

PubMed

Sawathiparnich, Pairunyar; Weerakulwattana, Linda; Santiprabhob, Jeerunda; Likitmaskul, Supawadee

2005-11-01

The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

Metabolic Concomitants of Obese and Nonobese Women With Features of Polycystic Ovarian Syndrome

PubMed Central

Boumosleh, Jocelyne Matar; Grundy, Scott M.; Phan, Jennifer; Neeland, Ian J.; Chang, Alice

2017-01-01

Context: Polycystic ovarian syndrome (PCOS) is often associated with obesity and diabetes. Objective: The present study measured body fat distribution and metabolic risk factors in women with features of PCOS. Design: Cross-sectional, multiethnic study of cardiovascular risks. Setting: General community. Study Participants: 145 PCOS and 344 non-PCOS women. Exposure Measures: Body composition by dual x-ray absorptiometry; abdominal fat masses measured by magnetic resonance imaging and hepatic triglyceride by magnetic resonance spectroscopy. Outcomes Measures: Body composition, liver fat content, homeostatic model assessment for insulin resistance (HOMA-IR), revised, and metabolic syndrome components. Results: PCOS women had a higher free androgen index compared with the non-PCOS women. Nonobese PCOS and non-PCOS women had a similar body fat content and distribution, HOMA-IR, and hepatic triglyceride content. Obese PCOS women had a similar total body fat percentage compared with their non-PCOS counterparts (41.4% and 41.4% respectively). Both obese groups had similar intraperitoneal fat (1.4% of total body mass in PCOS vs 1.4% in non-PCOS). However, obese PCOS women had a greater ratio of truncal/lower body fat (1.42 vs 1.27; P < 0.016). They also had greater insulin resistance (HOMA-IR: PCOS, 2.24% vs non-PCOS, 1.91%; P < 0.016), higher liver triglyceride content (6.96% in PCOS vs 4.44% in non-PCOS; P < 0.016), and a greater incidence of hypertension (33% vs 24%; P < 0.05). No differences were observed in other metabolic risk factors. Conclusions: Both obese and nonobese women with PCOS features had a greater free androgen index compared with non-PCOS women, but neither had greater intraperitoneal fat or abnormal lipid levels. Obese, but not nonobese, women with PCOS had a greater truncal/lower extremity fat ratio, HOMA-IR, and liver triglyceride content. PMID:29264465

Is cardiorespiratory fitness impaired in PCOS women? A review of the literature.

PubMed

Donà, S; Bacchi, E; Moghetti, P

2017-05-01

Polycystic ovary syndrome (PCOS) is a common and heterogeneous endocrine disorder, affecting 8-12% of reproductive-aged women. Insulin resistance and body fat excess are common features in these subjects. Increased physical activity and diet modifications are the first recommended approach in the management of these women, at least in overweight/obese subjects. Evaluation of cardiorespiratory fitness (CRF) is important in assessing exercise performance and in monitoring the effects of physical exercise interventions. Several studies have shown that CRF may be impaired in metabolic and endocrine disorders. However, there are little data on this issue in PCOS women. The aim of this narrative review is to critically evaluate whether aerobic capacity is altered in PCOS women, focusing on maximal oxygen uptake. An updated search of the literature was performed, identifying papers with maximal oxygen consumption measurements in women with PCOS compared to healthy controls. We have identified six studies on this specific topic: four of them showed an alteration of maximal oxygen consumption in PCOS women, whereas two did not. However, taken together these studies suggest that CRF may be strikingly impaired in both normal-weight and overweight/obese subjects with this condition. Women with PCOS appear to be characterized by a reduced cardiopulmonary fitness. However, further research on this topic is needed. This information may hopefully help clinicians and exercise specialist in planning individualized exercise programs aimed at improving the metabolic and endocrine outcomes in these women.

Prevalence and predictors of metabolic abnormalities in Chinese women with PCOS: a cross- sectional study

PubMed Central

2014-01-01

Background Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS. Methods A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures. Results The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p < 0.001) respectively. After adjusting for age, the indicators (central obesity, hypertension, fasting insulin, SHBG, dyslipinaemia) for metabolic disturbances were significantly higher in PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995). Conclusions The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance. PMID:25223276

Prevalence and predictors of metabolic abnormalities in Chinese women with PCOS: a cross- sectional study.

PubMed

Li, Rong; Yu, Geng; Yang, Dongzi; Li, Shangwei; Lu, Shulan; Wu, Xiaoke; Wei, Zhaolian; Song, Xueru; Wang, Xiuxia; Fu, Shuxin; Qiao, Jie

2014-09-16

Polycystic ovary syndrome (PCOS) is a common condition estimated to affect 5.61% of Chinese women of reproductive age, but little is known about the prevalence and predictors in Chinese PCOS patients. This study aimed to determine the prevalence and predictors of the metabolic abnormalities in Chinese women with and without PCOS. A large-scale national epidemiological investigation was conducted in reproductive age women (19 to 45 years) across China. 833 reproductive aged PCOS women, who participated in the healthcare screening, were recruited from ten provinces in China. Clinical history, ultrasonographic exam (ovarian follicle), hormonal and metabolic parameters were the main outcome measures. The prevalence of metabolic syndrome (MetS) as compared in PCOS and non-PCOS women from community were 18.2% vs 14.7%, and IR (insulin resistance) were 14.2% vs 9.3% (p < 0.001) respectively. After adjusting for age, the indicators (central obesity, hypertension, fasting insulin, SHBG, dyslipinaemia) for metabolic disturbances were significantly higher in PCOS than in non-PCOS groups. Using multivariate logistic regression, central obesity and FAI were risk factors, while SHBG was a protective factor on the occurrence of Mets and IR in PCOS women (OR: 1.132, 1.105 and 0.995). The risk factors of the metabolic syndrome and insulin resistance were BMI and FAI for PCOS women, respectively. The decrease of SHBG level was also a risk factor for insulin resistance in both PCOS and metabolic disturbance.

White blood cells levels and PCOS: direct and indirect relationship with obesity and insulin resistance, but not with hyperandogenemia.

PubMed

Papalou, Olga; Livadas, Sarantis; Karachalios, Athanasios; Tolia, Nikoleta; Kokkoris, Panayiotis; Tripolitakis, Konstantinos; Diamanti-Kandarakis, Evanthia

2015-01-01

To study white blood cells count (WBC) in women suffering from PCOS and compare these results with age and BMI-matched healthy women. The specific aim of this study was to assess the possible correlations of WBC with the major components of PCOS, obesity, insulin resistance and hyperandrogenism. Anthropometrical, metabolic and hormonal data were analyzed from 203 women with PCOS (NIH criteria) and 76 age-matched controls. In the total population studied (N=279), WBC was significantly higher (P=0.003) in the PCOS group compared with age-matched healthy women and was positively correlated with BMI (r=0.461, p<0.001), total testosterone (r= 0.210, p<0.001), insulin (r=0.271, p<0.001), triglycerides (r=0.285, p<0.001), HOMA score (r=0.206, p=0.001), FAI (r=0.329, p<0.001) and negatively correlated with SHBG (r=-0.300, p<0.001) and HDL (r=-0.222, p<0.001). Due to the fact that WHR was only available in the group of PCOS women, the role of central adiposity is assessed only in this group. Multiple regression analysis in the PCOS group, including WHR, revealed BMI, SHBG and TGL as the main predicting factors of WBC. Multinomial logistic regression analysis was also conducted and overweight/obesity was the sole independent risk factor for elevated WBC (higher tertile) (OR:0.907 CI:0.85-0.96, p=0.002). After dividing the sample based on BMI in the lean subgroups, WBC did not differ significantly between PCOS and controls, while multiple regression analysis indicated SHBG as the main predicting factor of WBC. Finally, we picked out the group of overweight/obese (BMI ≥25 kg/m2) women with PCOS and conducted another classification based on HOMA score (HOMA-IR≤2: insulin-sensitive women, HOMA-IR>2: insulin-resistant women) in the group of overweight and obese women with PCOS separately. In overweight women with PCOS, WBC, although higher in the group of insulin-resistant, did not differ significantly between the two groups, while in the subcategory of overweight women WBC

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS.

PubMed

Legro, Richard S; Dodson, William C; Kunselman, Allen R; Stetter, Christy M; Kris-Etherton, Penny M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Allison, Kelly C; Sarwer, David B; Diamond, Michael P; Schlaff, William D; Casson, Peter R; Christman, Gregory M; Barnhart, Kurt T; Bates, G Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Zhang, Heping; Eisenberg, Esther; Coutifaris, Christos; Dokras, Anuja

2016-07-01

In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Live birth, pregnancy loss, and ovulation were measured. In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01

Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

PubMed

Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

2008-09-01

Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS

PubMed Central

Dodson, William C.; Kunselman, Allen R.; Stetter, Christy M.; Kris-Etherton, Penny M.; Williams, Nancy I.; Gnatuk, Carol L.; Estes, Stephanie J.; Allison, Kelly C.; Sarwer, David B.; Diamond, Michael P.; Schlaff, William D.; Casson, Peter R.; Christman, Gregory M.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Zhang, Heping; Eisenberg, Esther; Coutifaris, Christos; Dokras, Anuja

2016-01-01

Context: In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. Objective: We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. Design, Setting, and Participants: This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18–40 years of age who were overweight/obese and infertile with PCOS. Intervention: We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Main Outcome Measures: Live birth, pregnancy loss, and ovulation were measured. Results: In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1–1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2–1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3–4

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model.

PubMed

Diane, Abdoulaye; Kupreeva, Maria; Borthwick, Faye; Proctor, Spencer D; Pierce, W David; Vine, Donna F

2015-09-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energy-restricted diet combined with or without voluntary exercise (4  h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (P<0.01). Energy restriction induced an increase in exercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of

Childhood Obesity and Its Impact on the Development of Adolescent PCOS

PubMed Central

Anderson, Amy D.; Solorzano, Christine M. Burt; McCartney, Christopher R.

2014-01-01

Obesity exacerbates the reproductive and metabolic manifestations of polycystic ovary syndrome (PCOS). The symptoms of PCOS often begin in adolescence, and the rising prevalence of peripubertal obesity has prompted concern that the prevalence and severity of adolescent PCOS is increasing in parallel. Recent data have disclosed a high prevalence of hyperandrogenemia among peripubertal adolescents with obesity, suggesting that such girls are indeed at risk for developing PCOS. Obesity may impact the risk of PCOS via insulin resistance and compensatory hyperinsulinemia, which augments ovarian/adrenal androgen production and suppresses sex hormone–binding globulin (SHBG), thereby increasing androgen bioavailability. Altered luteinizing hormone (LH) secretion plays an important role in the pathophysiology of PCOS, and although obesity is generally associated with relative reductions of LH, higher LH appears to be the best predictor of increased free testosterone among peripubertal girls with obesity. Other potential mechanisms of obesity-associated hyperandrogenemia include enhanced androgen production in an expanded fat mass and potential effects of abnormal adipokine/cytokine levels. Adolescents with PCOS are at risk for comorbidities such as metabolic syndrome and impaired glucose tolerance, and concomitant obesity compounds these risks. For all of these reasons, weight loss represents an important therapeutic target in obese adolescents with PCOS. PMID:24715515

Childhood obesity and its impact on the development of adolescent PCOS.

PubMed

Anderson, Amy D; Solorzano, Christine M Burt; McCartney, Christopher R

2014-05-01

Obesity exacerbates the reproductive and metabolic manifestations of polycystic ovary syndrome (PCOS). The symptoms of PCOS often begin in adolescence, and the rising prevalence of peripubertal obesity has prompted concern that the prevalence and severity of adolescent PCOS is increasing in parallel. Recent data have disclosed a high prevalence of hyperandrogenemia among peripubertal adolescents with obesity, suggesting that such girls are indeed at risk for developing PCOS. Obesity may impact the risk of PCOS via insulin resistance and compensatory hyperinsulinemia, which augments ovarian/adrenal androgen production and suppresses sex hormone-binding globulin (SHBG), thereby increasing androgen bioavailability. Altered luteinizing hormone (LH) secretion plays an important role in the pathophysiology of PCOS, and although obesity is generally associated with relative reductions of LH, higher LH appears to be the best predictor of increased free testosterone among peripubertal girls with obesity. Other potential mechanisms of obesity-associated hyperandrogenemia include enhanced androgen production in an expanded fat mass and potential effects of abnormal adipokine/cytokine levels. Adolescents with PCOS are at risk for comorbidities such as metabolic syndrome and impaired glucose tolerance, and concomitant obesity compounds these risks. For all of these reasons, weight loss represents an important therapeutic target in obese adolescents with PCOS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis.

PubMed

de Groot, P C M; Dekkers, O M; Romijn, J A; Dieben, S W M; Helmerhorst, F M

2011-01-01

Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients with PCOS and ovulatory women without PCOS, and assessed whether obesity might explain a higher risk of CHD or stroke. We performed a systematic review and meta-analysis of controlled observational studies. Four definitions of PCOS were considered: World Health Organization type II anovulation, National Institutes of Health criteria, Rotterdam consensus and Androgen-excess criteria. Obesity was defined as BMI > 30 kg/m(2) and/or waist circumference >88 cm. Study quality was assessed using the Newcastle-Ottawa Scale. Primary outcome was fatal/non-fatal CHD or stroke. Definitions of CHD and stroke were based on criteria used by the various authors. The effect measure was the pooled relative risk in a random effects model. Risk ratios and rate ratios were combined here. After identifying 1340 articles, 5 follow-up studies published between 2000 and 2008 were included. The studies showed heterogeneity in design, definitions and quality. In a random effects model the relative risk for CHD or stroke were 2.02 comparing women with PCOS to women without PCOS (95% confidence interval 1.47, 2.76). Pooling the two studies with risk estimates adjusted for BMI showed a relative risk of 1.55 (1.27, 1.89). This meta-analysis showed a 2-fold risk of arterial disease for patients with PCOS relative to women without PCOS. BMI adjustment did not affect this finding, suggesting the increased risk for cardiovascular events in PCOS is not completely related to a higher BMI in patients with PCOS.

Higher Circulating Leukocytes in Women with PCOS is Reversed by Aerobic Exercise

PubMed Central

Covington, Jeffrey D.; Tam, Charmaine S.; Pasarica, Magdalena; Redman, Leanne M.

2014-01-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r= -0.73, p=0.03; and r= -0.82, p=0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. PMID:25446648

Steroid hormone profiling in obese and nonobese women with polycystic ovary syndrome.

PubMed

Deng, Yuying; Zhang, Yifei; Li, Shengxian; Zhou, Wenzhong; Ye, Lei; Wang, Lihua; Tao, Tao; Gu, Junjie; Yang, Zuwei; Zhao, Dandan; Gu, Weiqiong; Hong, Jie; Ning, Guang; Liu, Wei; Wang, Weiqing

2017-10-26

The study explored differences in the steroidogenic pathway between obese and nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS (including 350 lean, 312 overweight and 382 obese) and 366 control women without PCOS (including 203 lean, 32 overweight and 131 obese) were enrolled. The differences in steroid hormones were amplified in lean PCOS versus lean controls compared with obese PCOS versus obese controls. Compared with obese PCOS, lean PCOS demonstrated increased dehydroepiandrosterone sulfate (P = 0.015), 17-hydropregnenolone (P = 0.003), 17-hydroprogesterone (17-OHP) (P < 0.001), progesterone (P < 0.001) and estrone (P < 0.001) levels. Enzyme activity evaluation showed that lean PCOS had increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P < 0.001), P450aro (P < 0.001), 3βHSD2 (progesterone/ pregnenolone and 17-OHP/17-hydropregnenolone, both P < 0.001) and decreased activity of P450c21(11-deoxycorticorsterone/progesterone and 11-deoxycortisol/17-OHP, P < 0.001). Moreover, we found higher frequencies of CYP21A2- (encoding P450c21) c.552 C > G (p. D184E) in lean PCOS compared with obese PCOS patients (P = 0.006). In conclusion, this study demonstrated for the first time that the adrenal-specific enzyme P450c21 showed decreased activity in lean PCOS patients, and that the adrenal androgen excess may play different roles in lean and obese PCOS patients, which represents as different enzyme activity in the steroidogenic pathway.

Dysregulation of glucose metabolism even in Chinese PCOS women with normal glucose tolerance.

PubMed

Li, Weiping; Li, Qifu

2012-01-01

To clarify the necessity of improving glucose metabolism in polycystic ovary syndrome (PCOS) women as early as possible, 111 PCOS women with normal glucose tolerance and 92 healthy age-matched controls were recruited to investigate glucose levels distribution, insulin sensitivity and β cell function. 91 PCOS women and 33 controls underwent hyperinsulinemic-euglycemic clamp to assess their insulin sensitivity, which was expressed as M value. β cell function was estimated by homeostatic model assessment (HOMA)-β index after adjusting insulin sensitivity (HOMA-βad index). Compared with lean controls, lean PCOS women had similar fasting plasma glucose (FPG), higher postprandial plasma glucose (PPG) (6.03±1.05 vs. 5.44±0.97 mmol/L, P<0.05), lower M value but similar HOMA-βad index, while overweight/obese PCOS women had higher levels of both FPG (5.24±0.58 vs. 4.90±0.39, P<0.05) and PPG (6.15±0.84 vs. 5.44±0.97 mmol/L, P<0.05), and lower levels of both M value and HOMA-βad index. Linear regression and ROC analysis found BMI was independently associated with M value and HOMA-βad index in PCOS women separately, and the cutoff of BMI indicating impaired β cell function of PCOS women was 25.545kg/m². In conclusion, insulin resistance and dysregulation of glucose metabolism were common in Chinese PCOS women with normal glucose tolerance. BMI ≥ 25.545kg/m² indicated impaired β cell function in PCOS women with normal glucose tolerance.

Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet

PubMed Central

Amiri, Mania; Golsorkhtabaramiri, Masoumeh; Esmaeilzadeh, Sedigheh; Ghofrani, Faeze; Bijani, Ali; Ghorbani, Leila; Delavar, Moloud Agajani

2014-01-01

Background This study was designed to investigate the effect of metformin and flutamide alone or in combination with anthropometric indices and laboratory tests of obese/overweight PCOS women under hypocaloric diet. Methods This single blind clinical trial was performed on 120 PCOS women. At the beginning, hypocaloric diet was recommended for the patients. After one month while they were on the diet, the patients were randomly divided in 4 groups; metformin (500 mg, 3/day), flutamide (250 mg, 2/day), combined, metformin (500 mg, 3/day) with flutamide (250 mg, 2/day) and finally placebo group. The patients were treated for 6 months. Anthropometric indices and laboratory tests (fasting and glucose-stimulated insulin levels, lipid profile and androgens) were measured. A one-way ANOVA (Post Hoc) and paired t-test were performed to analyze data. A p ≤ 0.05 was considered statistically significant. Results After treatment, reduction in weight, BMI, hip circumference was significantly greater in the metformin group in comparison to other groups (p<0.05). In addition, the fasting insulin was significantly greater in metformin group and flutamide group in comparison to metformin+flutamide and placebo groups after treatment (p<0.05). Within groups, insulin level showed significant changes (before and after treatment) in metformin+flutamide group and LDL reduction was significant in flutamide group before and after treatment. Post hoc tukey and two-tailed with p≤0.05 were used to define statistical significance. Conclusion Using combination of metformin and flutamide improves anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet. PMID:25473629

Effect of Metformin and Flutamide on Anthropometric Indices and Laboratory Tests in Obese/Overweight PCOS Women under Hypocaloric Diet.

PubMed

Amiri, Mania; Golsorkhtabaramiri, Masoumeh; Esmaeilzadeh, Sedigheh; Ghofrani, Faeze; Bijani, Ali; Ghorbani, Leila; Delavar, Moloud Agajani

2014-10-01

This study was designed to investigate the effect of metformin and flutamide alone or in combination with anthropometric indices and laboratory tests of obese/overweight PCOS women under hypocaloric diet. This single blind clinical trial was performed on 120 PCOS women. At the beginning, hypocaloric diet was recommended for the patients. After one month while they were on the diet, the patients were randomly divided in 4 groups; metformin (500 mg, 3/day), flutamide (250 mg, 2/day), combined, metformin (500 mg, 3/day) with flutamide (250 mg, 2/day) and finally placebo group. The patients were treated for 6 months. Anthropometric indices and laboratory tests (fasting and glucose-stimulated insulin levels, lipid profile and androgens) were measured. A one-way ANOVA (Post Hoc) and paired t-test were performed to analyze data. A p ≤ 0.05 was considered statistically significant. After treatment, reduction in weight, BMI, hip circumference was significantly greater in the metformin group in comparison to other groups (p<0.05). In addition, the fasting insulin was significantly greater in metformin group and flutamide group in comparison to metformin+flutamide and placebo groups after treatment (p<0.05). Within groups, insulin level showed significant changes (before and after treatment) in metformin+flutamide group and LDL reduction was significant in flutamide group before and after treatment. Post hoc tukey and two-tailed with p≤0.05 were used to define statistical significance. Using combination of metformin and flutamide improves anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet.

In women with PCOS, waist circumference is a better surrogate of glucose and lipid metabolism than disease status per se.

PubMed

Pazderska, Agnieszka; Kyaw Tun, Tommy; Phelan, Niamh; McGowan, Anne; Sherlock, Mark; Behan, LucyAnn; Boran, Gerard; Gibney, James

2018-04-01

Cardiometabolic abnormalities are recognized in polycystic ovary syndrome (PCOS). However, over-emphasis on PCOS as a risk factor potentially results in over-investigation and treatment of some women with and under-recognition of cardiometabolic risk in obese women without PCOS. Our objective was to explore the association between waist circumference (WC) and indices of glucose and lipid metabolism in women with and without PCOS. (i) An exploratory cross-sectional study investigating association of potential cardiometabolic risk markers (PCOS status, anthropometric measures, hsCRP, HOMA-IR, SHBG, testosterone) with indices of glucose (frequently sampled intravenous glucose tolerance test) and lipid metabolism (postprandial studies and lipoprotein particle size) in 61 women with (n = 29) and without (n = 32) PCOS; (ii) a cross-sectional study in 103 PCOS women and 102 BMI-matched controls to explore if between-group differences in indices of lipid and glucose metabolism persist after adjusting for WC. NIH criteria were used for PCOS diagnosis. Study 1: Univariate correlations and stepwise regression modelling identified waist circumference (WC), as a better surrogate than PCOS status, independently predicting multiple variables of glucose and lipid metabolism. Study 2: Fasting insulin and triglyceride, hsCRP and insulin resistance (according to HOMA-IR and SiM [Avignon index]) were greater, while fasting HDL was lower in women with PCOS compared to BMI-matched women without PCOS. None of these differences persisted when a subset of 80 women with PCOS was compared with 80 women without PCOS, pair-matched for WC. Some cardiometabolic abnormalities in PCOS are related to central obesity, and following adjustment for WC does not differ from normal subjects. Waist circumference measurement has potential to take precedence over PCOS status as part of the assessment of cardiometabolic risk in reproductive-age women. © 2017 John Wiley & Sons Ltd.

Pro12Ala PPAR γ2 gene polymorphism in PCOS women: the role of compounds regulating satiety.

PubMed

Bidzińska-Speichert, Bożena; Lenarcik, Agnieszka; Tworowska-Bardzińska, Urszula; Slęzak, Ryszard; Bednarek-Tupikowska, Grażyna; Milewicz, Andrzej

2012-03-01

Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels. In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.

Surgical management of metabolic dysfunction in PCOS.

PubMed

Escobar-Morreale, Héctor F

2012-03-10

Metabolic disturbances are common in women with polycystic ovary syndrome (PCOS). Obesity is the major link in the association of PCOS with diabetes, metabolic syndrome, hypertension, low-grade chronic inflammation and increased body iron stores, among others. Metabolic prevention in PCOS women should start as early as possible, usually meaning at diagnosis. Among preventive strategies, those promoting a healthy life-style based on diet, regular exercising and smoking cessation are possibly the most effective therapies, but also are the most difficult to achieve. To this regard, every effort must be made to avoid weight gain and obesity, given the deleterious impact that obesity exerts on the metabolic and cardiovascular associations of PCOS. Unfortunately, classic strategies that address obesity by life-style modification and dieting are seldom successful on a long-term basis, especially in women with severe obesity. In selected cases, metabolic surgery in severely obese women may resolve signs and symptoms of PCOS restoring insulin sensitivity and fertility, and avoiding the long-term risks associated with PCOS and morbid obesity. Surgical techniques for bariatric surgery have evolved in the past decades and newer procedures do not longer carry the severe side effects associated with earlier bariatric procedures. The choice of bariatric procedure should consider both the severity of obesity and the possibility of future pregnancy, since fertility may be restored by the sustained and marked weight loss usually attained after bariatric surgery. Finally, avoidance of the risks associated with morbid obesity compensate for the possible residual risks for pregnancy derived from the previous bariatric procedure itself. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome.

PubMed

Velija-Ašimi, Zelija

2014-02-01

To evaluate the association of vitamin D (VD) deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome (PCOS). Of the total of 140 women, thirty obese and thirty nonobese, aged 20-40 years, were included in the study. Inclusion criteria were the women with normal level of thyroid-stimulating hormone (TSH), prolactin (PRL), parathyroid hormone (PTH), and calcium, and those who had not received any medication or VD supplementation within the last 6 months. Serum 25- hydroxyvitamin D (25(OH)D), C-reactive protein (CRP), lipid profile, fasting serum glucose, basal insulin, homeostasis model analysis of insulin resistance (HOMA-IR) index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, total testosterone, dehidroepiandrostendion-sulphat (DHEA-S), androstendione, and sex hormone binding globulin (SHBG) were determined at follicular phase. Body mass index (BMI), weight, waist, lipids, and CRP were significantly higher in obese than in non-obese PCOS women (p=0.000). Meanwhile, insulin and HOMA-IR were also higher in the obese PCOS (p less than 0.000), and so was the fasting glucose (p=0.004). Furthermore, obese PCOS showed significantly higher level of LH (p=0.012), but lower level of progesterone (p=0.001) and androstendione (p=0.006) than in non-obese PCOS. In total 68% of PCOS women had VD deficiency but without significant difference among groups according to BMI. There was no association of VD deficiency with gonadotropins and sex hormones except SHBG. Insulin resistance was a better independent risk factor for the presence of vitamin D deficiency than SHBG. The insulin resistance and vitamin D deficiency significantly predicted the obesity risk in PCOS women.

Clinical, hormonal and metabolic characteristics of polycystic ovary syndrome among obese and nonobese women in the Croatian population.

PubMed

Baldani, Dinka Pavicić; Skrgatić, Lana; Goldstajn, Marina Sprem; Vrcić, Hrvoje; Canić, Tomislav; Strelec, Mihajlo

2013-06-01

Obesity has a deteriorating impact on women with PCOS, although prevalence and the impact of specific traits of PCOS remain inconstant in different populations. Therefore, the aim of this study was to explore the differences in clinical, hormonal and metabolic features between obese and nonobese Croatian women diagnosed as having PCOS according to Rotterdam consensus criteria. The study included 74 obese and 208 nonobese women with PCOS. Clinical, biochemical and metabolic variables were compared among those PCOS subgroups. Obese subjects with PCOS had a higher risk of developing oligo-amenorrhea (OR 3.7; 95% CI, 1.1-12.5) and lower risk for developing hirsutism and acne (OR 0.2; 95% CI, 0.1-0.3 and OR 0.8; 95% CI 0.5-1.4, respectively). Obese PCOS subjects also had a higher risk of developing hyperandrogenemia (OR 2.5; CI 95% 0.9-6.7), insulin resistance (OR 4.5; CI 95%, 2.6-7.9), hypercholesterolemia (OR 5.0, CI 95% 2.5-10.2), hypertriglyceridemia (OR 5.2; 95% CI, 2.9-9.2) as well as elevated serum CRP levels (OR 4.1; 95% CI 1.4-12.2) compared to nonobese PCOS women. In conclusion, nonobese Croatian women with PCOS are more inclined to cosmetic problems associated with PCOS then metabolic ones. This is the first study to report the impact of obesity on acne and irregular menses as a study outcome. Obesity deteriorates menstrual regularity, insulin sensitivity and lipid profile in Croatian women with PCOS; therefore one of the fundamental treatment strategies of PCOS should be obesity prevention.

Cortisol production rate is similarly elevated in obese women with or without the polycystic ovary syndrome.

PubMed

Roelfsema, Ferdinand; Kok, Petra; Pereira, Alberto M; Pijl, Hanno

2010-07-01

The pituitary-adrenal axis in obesity and polycystic ovary syndrome (PCOS) is marked by increased urinary excretion of cortisol and its metabolites. It is not as yet clear whether the increased cortisol production in PCOS is related to obesity per se. We investigated 15 obese PCOS women with a body mass index of 30-54 kg/m(2) and 15 healthy obese controls (body mass index 31-60 kg/m(2)) with a regular menstrual cycle. Patients and control women underwent 24-h blood sampling at 20-min intervals. Cortisol concentrations were measured with a sensitive assay. Data were analyzed with a new deconvolution program, approximate entropy, and cosinor regression. Basal, pulsatile, and total cortisol production expressed per liter distribution volume, per square meter body surface, and as absolute amount per 24 h was similar in PCOS patients and matched healthy control women. In addition, the regularity of cortisol secretion and the diurnal properties were identical. Compared with 10 lean control women, mean cortisol production per liter distribution volume was similar in the three groups, but the total 24-h cortisol production was increased in obese control women and PCOS women. This study demonstrates equally increased cortisol production in PCOS women and obese healthy control women.

Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS.

PubMed

Bayrak, Tulin; Dursun, Polat; Bayrak, Ahmet; Gültekin, Murat; Kolusarı, Ali; Cakır, Erdinç; Ozyurt, Merve; Zeyneloğlu, Hulusi B

2012-11-01

Paraoxonase1 (PON1), exhibits both esterase activity (PON1-AREase) and homocysteine thiolactonase activity (PON1-HTLase) which respectively prevent LDL oxidation and detoxify homocysteine thiolactone (HTL). Platelet-activating factor-acetylhydrolase (PAF-AH) is an antioxidant enzyme preventing LDL oxidation by hydrolysis of oxidized phospholipids. Both of these enzymes exhibit a proatherogenic role. ADMA is an endogenous inhibitor of nitric oxide (NO) synthesis causing endothelial dysfunction. The aim was to compare non-obese PCOS patients with a BMI matched control group using the following characteristics: serum PON1-HTLase, ADMA, PAF-AH, and lipid and hormonal parameters. 77 women with PCOS and 25 healthy subject were recruited for this study, The controls were non-obese BMI and age matched with the patients. There were no significant differences with respect to age, BMI, FSH, free testosterone, DHEA, androstenadion, total cholesterol, triglycerides, HDL, LDL, VLDL, fasting glucose/insulin ratio and HOMA-IR among the groups (p > 0.05). However, total testosterone and fasting glucose levels were significantly higher in the PCOS group (p < 0.05). On the other hand, PON1-HTLase levels (39.6 ± 5.77 vs. 33.8 ± 8.2, p = 0.02) were significantly lower in the PCOS group while ADMA levels (1.14 ± 0.6 vs. 3.37 ± 6.4, p = 0.004) were significantly higher in the PCOS group. However, there was no significant difference in PAF-AH activity among the groups. Decreased PON1-HTLase and increased ADMA levels might be a relevant marker for the development of future atherosclerotic heart disease (AHD) in non-obese PCOS patients. Further studies are needed to confirm our results.

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

PubMed

Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

2016-01-01

To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Cross-sectional comparison of serum biomarkers. University Medical Center Utrecht. Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30). Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing. In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory

Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

PubMed Central

Daan, Nadine M. P.; Koster, Maria P. H.; de Wilde, Marlieke A.; Dalmeijer, Gerdien W.; Evelein, Annemieke M. V.; Fauser, Bart C. J. M.; de Jager, Wilco

2016-01-01

Objective To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Design Cross-sectional comparison of serum biomarkers. Setting University Medical Center Utrecht. Patients Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6–8 years), and a paedriatic reference population (n = 30). Main Outcome Measure(s) Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). Results The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing. Conclusion In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with

Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms: 15-Year Follow-Up.

PubMed

Karjula, Salla; Morin-Papunen, Laure; Auvinen, Juha; Ruokonen, Aimo; Puukka, Katri; Franks, Stephen; Järvelin, Marjo-Riitta; Tapanainen, Juha S; Jokelainen, Jari; Miettunen, Jouko; Piltonen, Terhi T

2017-06-01

Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Population-based follow-up. Northern Finland Birth Cohort 1966 with 15-year follow-up. At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression. Copyright © 2017 by the Endocrine Society

Diagnosis and follow-up of type 2 diabetes in women with PCOS. A role of OGTT?

PubMed

Andersen, Marianne Skovsager; Glintborg, Dorte

2018-06-19

Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and the high sensitivity of the 2 hour glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM, however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

The effect of prolactin levels on MPV in women with PCOS.

PubMed

Yilmaz, Özgür; Calan, Mehmet; Kume, Tuncay; Temur, Muzaffer; Yesil, Pınar; Senses, Mehmet Y

2015-05-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk factors including hypertension, obesity, hyperlipidaemia and glucose intolerance. Several studies demonstrated the link between PCOS and an increased risk of cardiovascular disease. Platelets play a crucial role in the development of atherothrombotic disease. Mean platelet volume (MPV) is a marker of platelet size that reflects its activity. Research points to a link between prolactin (PRL) and platelet activation. The purpose of this study was to investigate whether prolactin levels are associated with MPV in women with PCOS. The research was designed as a cross-sectional study. Participants were divided into three groups-PCOS patients with mildly elevated PRL levels (n = 72), patients with PCOS with normal PRL levels (n = 207) and healthy controls (n = 90). They were body mass index and age-matched and consecutively recruited. Complete blood counts, serum glucose, prolactin, insulin, lipids, high-sensitivity C-reactive protein and free-testosterone levels were measured. Among the three groups, MPV levels were higher in women with PCOS having mildly elevated PRL levels (P < 0·001) and MPV was found to be correlated with PRL levels (r = 0·387, P < 0·001). Multiple regression analysis showed that PRL levels were associated with MPV levels (R(2) = 0·239, β = 0·354, P < 0·001). Mean platelet volume levels are significantly increased in women with PCOS having mildly elevated PRL. Our results suggest that there is a link between prolactin and MPV levels. In women with PCOS, elevated PRL levels may increase the risk of developing atherothrombotic events via the activation of platelets. © 2014 John Wiley & Sons Ltd.

Bariatric Surgery Reduces Serum Anti-mullerian Hormone Levels in Obese Women With and Without Polycystic Ovarian Syndrome.

PubMed

Chiofalo, Francesco; Ciuoli, Cristina; Formichi, Caterina; Selmi, Federico; Forleo, Raffaella; Neri, Ornella; Vuolo, Giuseppe; Paffetti, Patrizia; Pacini, Furio

2017-07-01

Obesity in fertile women has negative effect on fertility. Anti-mullerian hormone (AMH) represents a good index of fertility, and it is considered a marker of ovarian reserve and of polycystic ovarian syndrome (PCOS) gravity. Previous studies evaluated the relationship between obesity and AMH with contradictory results. The aim of the study was to investigate the relationship between obesity and AMH and the changes of AMH in obese women in reproductive age submitted to bariatric surgery. Fifty-five obese patients between 18 and 39 years with (29 patients) and without PCOS (26 patients) were compared with a control group of normal weight women with (24 patients) and without PCOS (19 patients). Fourteen obese women with PCOS and 18 without PCOS underwent to bariatric surgery. Serum AMH, testosterone, androstenedione, and DHEAS were performed in all patients before and 1 year after surgical intervention. AMH was significantly higher in the PCOS groups (p < 0.001), both in obese (5.84 ± 3.94 ng/ml) and non-obese women (7.35 ± 4.39 ng/ml). AMH was positively related to testosterone (p < 0.0001), androstenedione (p = 0.0005), and DHEAS (p = 0.003). After bariatric surgery, AMH levels were reduced in the both PCOS (p = 0.02) and non-PCOS group (p = 0.04). AMH levels are elevated in PCOS patients regardless of the body weight. Bariatric surgery is effective in the normalization of AMH levels (a possible indirect marker of better fertility) only in obese patients with PCOS.

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss.

PubMed

Reinehr, Thomas; Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

2017-05-01

The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC-MS/MS steroid profiling at baseline and one year later. At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. © 2017 The authors.

LATE-NIGHT SALIVARY CORTISOL IS UNALTERED IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS), IRRESPECTIVE OF DISEASE PHENOTYPE, AND IN OBESE WOMEN, IRRESPECTIVE OF THE PRESENCE OF PCOS.

PubMed

Ozkaya, Hande Mefkure; Keskin, Fatma Ela; Tuten, Abdullah; Korkmaz, Ebru; Oktay, Hulya Zeynep; Kadioglu, Pinar

2017-09-01

To determine cutoff values of late-night salivary cortisol (LNSC) using an electrochemiluminescent immunoassay and investigate whether the diagnostic performance of the assay is influenced by the presence of obesity or polycystic ovary syndrome (PCOS). A total of 124 subjects comprising 25 patients with Cushing syndrome (CS), 44 with PCOS (22 nonobese and 22 obese), 21 with constitutional obesity (CO), and 34 healthy subjects (HS) were included in the study. Two consecutive LNSC samples were collected from all participants. The median LNSC levels of patients with CS were significantly higher than LNSC levels of HS, patients with CO, and obese and nonobese patients with PCOS, respectively (P<.01 for all). Healthy subjects, patients with CO, and obese and nonobese patients with PCOS did not differ in terms of median LNSC levels (P>.05 for all). The cutoff values and corresponding sensitivity and specificity were similar between the groups. The comparisons of the area under curve of the first LNSC (0.963; 95% confidence interval [CI], 0.910 to 0.989), second LNSC (0.954; 95% CI, 0.898 to 0.984), and the mean of two consecutive LNSC (mLNSC) values (0.962; 95% CI, 0.909 to 0.989) did not differ significantly (P>.05 for all). A cutoff value for mLNSC of 7.45 nmol/L yielded a sensitivity of 100% and specificity of 87.5% in HS. In conclusion, LNSC is a reliable test with high diagnostic accuracy in both HS and patients with PCOS and obesity. ACTH = adrenocorticotropic hormone AUC = area under the curve BMI = body mass index CO = constitutional obesity CS = Cushing syndrome E2 = estradiol ECLIA = electrochemiluminescent immunoassay FPG = fasting plasma glucose FSH = follicle-stimulating hormone HOMA-IR = homeostasis model assessment of insulin resistance HPA = hypothalamo-pituitary-adrenal HS = healthy subjects IQR = interquartile range LH = luteinizing hormone LNSC = late-night salivary cortisol LR = likelihood ratio mLNSC = mean of two consecutive LNSC samples PCOS

Increased follistatin levels after oral contraceptive treatment in obese and non-obese women with polycystic ovary syndrome.

PubMed

Chen, Mei-Jou; Yang, Wei-Shiung; Chen, Hsin-Fu; Kuo, Jahn-Jahn; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Shee-Uan

2010-03-01

Follistatin levels have recently been considered as a marker for inflammation. Our objective was to evaluate the level of circulating follistatin and high-sensitivity C-reactive protein (hsCRP) in women with polycystic ovary syndrome (PCOS) after oral contraceptive (OC) treatment. A total of 56 Taiwanese women with PCOS were enrolled in this prospective observational study in which they were treated for 3 months with OCs (ethinyl estradiol-cyproterone acetate). Blood samples were taken at baseline after treatment during the withdrawal bleed. Body mass index (BMI), lipid profiles, plasma follistatin, hsCRP, fasting glucose, insulin for the homeostasis model assessment of insulin resistance (HOMA-IR) and hormone profiles were measured and analyzed. Total testosterone, free androgen index (FAI), dehydroepiandrosterone sulfate (DHEAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels were significantly lower, but total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, circulating follistatin and hsCRP were significantly higher than baseline in women with PCOS after treatment with OCs. An elevation of fasting insulin, HOMA-IR and hsCRP after OC treatment was more evident in non-obese than obese women, whereas the elevation of follistatin was significant in both obese and non-obese women. Follistatin and hsCRP levels all showed significant correlations with each other at baseline and after treatment. The differences in follistatin and hsCRP levels from baseline to after OC treatment were significantly associated with the difference in triglyceride levels. Both hsCRP and follistatin levels increase after OC treatment in women with PCOS. Follistatin seems more sensitive than hsCRP alone to represent the aggravated low-grade inflammatory status after OC treatment in obese and non-obese women with PCOS.

Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss

PubMed Central

Kulle, Alexandra; Rothermel, Juliane; Knop-Schmenn, Caroline; Lass, Nina; Bosse, Christina; Holterhus, Paul-Martin

2017-01-01

Objective The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. Design This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status. Methods We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later. Results At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. Conclusions The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS. PMID:28373267

Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise.

PubMed

Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena; Redman, Leanne M

2016-05-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r = -0.73, p = 0.03; and r = -0.82, p = 0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. Copyright �

Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms: 15-Year Follow-Up

PubMed Central

Karjula, Salla; Morin-Papunen, Laure; Auvinen, Juha; Ruokonen, Aimo; Puukka, Katri; Franks, Stephen; Järvelin, Marjo-Riitta; Tapanainen, Juha S.; Jokelainen, Jari; Miettunen, Jouko

2017-01-01

Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression. PMID:28323926

Dyslipidemia in PCOS.

PubMed

Wild, Robert A

2012-03-10

Life-long apolipoprotein lipid metabolic dysfunction in women with PCOS exaggerates the risk for cardiovascular disease (CVD) with aging. The dysfunction has involved insulin resistance (IR), which occurs in most women with PCOS. Women with PCOS have androgen excess, IR, variable amounts of estrogen exposure, and many environmental factors, all of which can influence lipid metabolism. On average, women with PCOS were higher triglyceride [26.39 95% CI (17.24, 35.54)], lower HDL-cholesterol [6.41 95% CI (3.69, 9.14)], and higher non HDL cholesterol levels [18.82 95% CI (15.53, 22.11)] than their non-PCOS counterparts. They have higher ApoCIII/ApoCII ratios and higher ApoCI even if they are not obese. ApoC1 elevation in women with PCOS needs to be further evaluated as a marker of dysfunction and potential CVD risk. ApoB measurements track with non-HDL cholesterol as a surrogate for increased atherogenic circulating small LDL particles. Elevated triglycerides and waist circumference predict CVD risk and women with PCOS often have these phenotypes. Diet and exercise interventions followed by selective lipid lowering medications are encouraged to normalize the dyslipidemia. Copyright © 2012 Elsevier Inc. All rights reserved.

The incretin effect and secretion in obese and lean women with polycystic ovary syndrome: a pilot study.

PubMed

Pontikis, Charalambos; Yavropoulou, Maria P; Toulis, Konstantinos A; Kotsa, Kalliopi; Kazakos, Kyriakos; Papazisi, Aleka; Gotzamani-Psarakou, Anna; Yovos, John G

2011-06-01

Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS. Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed. Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women. Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis.

Practice Patterns in Screening for Metabolic Disease in Women with PCOS of Diverse Race-Ethnic Backgrounds.

PubMed

Mott, Melanie M; Kitos, Nicole R; Coviello, Andrea D

2014-09-01

Women with polycystic ovary syndrome (PCOS) are at high risk for metabolic disorders, which prompted the American Association of Clinical Endocrinologists (AACE) to publish a 2005 position statement recommending screening for metabolic disease.The purposes of the present study were to 1) to examine changes in screening rates for obesity, type 2 diabetes (T2D), metabolic syndrome (MetS), hyperlipidemia (HL), nonalcoholic fatty liver disease (NAFLD), and hypertension (HTN) in women with PCOS after publication of the 2005 AACE position statement and 2) to determine if screening rates and metabolic disorders vary by race-ethnicity. PCOS cases in 2006 (n = 547) and 2011 (n = 1,159) and metabolic disorders were identified by International Classification of Diseases, 9th revision (ICD9) code. Screening rates for metabolic disorders were determined by the presence of blood tests (hemoglobin A1c [HbA1c], lipid profile, alanine aminotransferase/aspartate aminotransferase [ALT/AST]). In 2006, ≤25% of PCOS patients underwent recommended screening tests: HbA1c 18%; lipid profile <20%; ALT/AST ≤25%. By 2011, only HbA1c testing had increased (18% to 21%). Obesity increased from 35% to 40%, while other metabolic disorders remained stable. Black women had the highest rates of obesity and HTN in 2011 (Obesity: Black 48%, Hispanic 44%, White 33%, Other 31%, P<.0001; HTN: Black 18%, Hispanic 9%, White 10%, Other 7%, P<.0001). Blacks and Hispanics were screened more often with ALT/AST testing (Black 27/27%, Hispanic 28/27%, White 23/22%, Other 17/18%, P = .02/.03). Screening rates were higher in the endocrine clinic for all metabolic disorders than in other clinics (P<.05). Despite the publication of recommendations in 2005, screening rates for metabolic disease in women with PCOS remained low across all race-ethnicities in 2011.

Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS).

PubMed

Borruel, Susana; Fernández-Durán, Elena; Alpañés, Macarena; Martí, David; Alvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2013-03-01

Sexual dimorphism suggests a role for androgens in body fat distribution. Women with polycystic ovary syndrome (PCOS), a mainly androgen excess disorder, often present with abdominal obesity and visceral adiposity. We hypothesized that women with PCOS have a masculinized body fat distribution favoring the deposition of fat in visceral and organ-specific adipose tissue depots. This was a case-control study. The study was conducted at an academic hospital. Women with PCOS (n = 55), women without androgen excess (n = 25), and men (n = 26) presenting with similar body mass index participated in the study. There were no interventions. Ultrasound measurements of adipose tissue depots including sc (minimum and maximum), preperitoneal, ip, mesenteric, epicardial, and perirenal fat thickness were obtained and total body fat mass was estimated using a body fat monitor. Men and patients with PCOS had increased amounts of total body fat compared with control women. Men had increased thickness of intraabdominal adipose tissue depots compared with the control women, with the women with PCOS showing intermediate values that were also higher than those of control women in the case of ip and mesenteric fat thickness and was close to reaching statistical significance in the case of epicardial fat thickness. Women with PCOS also showed increased minimum sc fat thickness compared with the control women. Obesity increased the thickness of all of the adipose tissue depots in the 3 groups of subjects. Women with PCOS have higher global adiposity and increased amounts of visceral adipose tissue compared with control women, especially in the ip and mesenteric depots.

Diet, physical exercise and Orlistat administration increase serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

PubMed

Vosnakis, Christos; Georgopoulos, Neoklis A; Rousso, David; Mavromatidis, Georgios; Katsikis, Ilias; Roupas, Nikolaos D; Mamali, Irene; Panidis, Dimitrios

2013-03-01

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Beta endorphin in serum and follicular fluid of PCOS- and non-PCOS women.

PubMed

Jaschke, Nikolai; Lunger, Fabian; Wildt, Ludwig; Seeber, Beata

2018-07-01

To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters. Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol. There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels. Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

Quality of life in overweight (obese) and normal-weight women with polycystic ovary syndrome

PubMed Central

Panico, Annalisa; Messina, Giovanni; Lupoli, Gelsy Arianna; Lupoli, Roberta; Cacciapuoti, Marianna; Moscatelli, Fiorenzo; Esposito, Teresa; Villano, Ines; Valenzano, Anna; Monda, Vincenzo; Messina, Antonietta; Precenzano, Francesco; Cibelli, Giuseppe; Monda, Marcellino; Lupoli, Giovanni

2017-01-01

Objective Polycystic ovary syndrome (PCOS) is characterized by phenotypic heterogeneity and has a wide variety of consequences. Approximately half of women with PCOS are overweight or obese, and their obesity may be a contributing factor to PCOS pathogenesis through different mechanisms. The aim of this study was to evaluate if PCOS alone affects the patients’ quality of life and to what extent obesity contributes to worsen this disease. Design To evaluate the impact of PCOS on health-related quality-of-life (HRQoL), 100 Mediterranean women with PCOS (group A), 50 with a body mass index (BMI) >25 kg/m2 (group A1) and 50 with BMI <25 kg/m2 (group A2), were recruited. They were evaluated with a specific combination of standardized psychometric questionnaires: the Symptom Checklist-90 Revised, the 36-Item Short-Form Health Survey, and the Polycystic Ovary Syndrome Questionnaire. The patients were compared with a normal-weight healthy control group of 40 subjects (group B). Another control group of 40 obese healthy women (group C) was used to make a comparison with PCOS obese patients (A1). Results Our results showed a considerable worsening of HRQoL in PCOS patients (A) compared with controls (B). In addition, patients with PCOS and BMI >25 (A1) showed a significant and more marked reduction in scores, suggesting a lower quality of life, compared with controls (B) and with normal-weight PCOS patients (A2). Conclusion PCOS is a complex disease that alone determines a deterioration of HRQoL. The innovative use of these psychometric questionnaires in this study, in particular the PCOS questionnaire, has highlighted that obesity has a negative effect on HRQoL. It follows that a weight decrease is associated to phenotypic spectrum improvement and relative decrement in psychological distress. PMID:28280314

The effect of obesity on inflammatory markers in patients with PCOS: a BMI-matched case-control study.

PubMed

Keskin Kurt, Raziye; Okyay, Ayşe Güler; Hakverdi, Ali Ulvi; Gungoren, Arif; Dolapcioglu, Kenan Serdar; Karateke, Atilla; Dogan, Mustafa Ozcil

2014-08-01

Previous studies have shown increased inflammatory activity in patients with polycystic ovary syndrome (PCOS); however, it remains uncertain whether this increased inflammatory activity is a consequence of the disorder itself or of the accompanying obesity. We therefore aimed to test the inflammatory marker levels in obese and lean patients with PCOS by using two separate control groups with matching body mass index (BMI). A total of 120 women in reproductive age with (n = 62) and without (n = 60) PCOS were recruited for the study. Patients with PCOS were divided into two groups as obese (n = 32) and lean (n = 30) PCOS groups according to BMI. Two BMI-matched control groups were created. Furthermore, high sensitive CRP protein (hsCRP), neutrophils, lymphocytes, white blood cell count (WBC) and neutrophil to lymphocyte ratio (NLR) were evaluated with complete blood count. The hsCRP (5.5 ± 0.8 vs. 3.1 ± 0.7, p < 0.001), neutrophil count (3.8 ± 0.4 vs. 2.9 ± 0.7, p < 0.001), leukocyte count (7.2 ± 1.8 vs. 5.6 ± 1.6, p < 0.001), and NLR (2.6 ± 1.4 vs. 1.5 ± 0.4, p < 0.001) were higher in patients with PCOS compared to the control group while lymphocyte count was lower (1.71 ± 0.65 vs. 1.98 ± 0.39, p = 0.008). Similarly, both obese and lean patients with PCOS had higher levels of hsCRP, neutrophils, leukocytes and NLR ratios compared to BMI-matched controls. The correlation analysis revealed a moderate correlation between NLR and hsCRP (r 0.459, p < 0.001), and between HOMA-IR (r 0.476 p < 0.001) and BMI (r 0.310, p 0.001). Our study results demonstrated that both lean and obese patients with PCOS have increased inflammatory markers compared to BMI-matched control groups indicating that the inflammation seen in PCOS might be related with the presence of the disorder rather than with obesity.

Predictive value of glucose-insulin ratio in PCOS and profile of women who will benefit from metformin therapy: obese, lean, hyper or normoinsulinemic?

PubMed

Onalan, Gogsen; Goktolga, Umit; Ceyhan, Temel; Bagis, Tayfun; Onalan, Reside; Pabuçcu, Recai

2005-12-01

The aim of the present study is to evaluate sub-groups of PCOS patients who will benefit from metformin therapy and to find out any predictors of ovulation in PCOS sub-groups. In the current prospective-randomized, placebo-controlled, double-blind study, PCOS patients (n = 116) were divided into six main groups according to glucose to insulin ratio (G-I ratio mg/10(-4) U) and body mass index (BMI kg/m2) as: Group 1: normoinsulinemic (G-I ratio > or = 4.5 mg/10(-4) U), lean (BMI < 25) (n = 37); Group 2: normoinsulinemic, overweight (BMI: 25-29.9) (n = 19); Group 3: normoinsulinemic, obese (BMI > or = 30) (n = 18); Group 4: hyperinsulinemic (G-I ratio < 4.5 mg/10(-4) U), lean (n = 28); Group 5: hyperinsulinemic, overweight (n = 17); Group 6: hyperinsulinemic, obese (n = 20). Patients in each group were randomized onto placebo or metformin treatments (850 mg two to three times per day according to BMI). The rate of ovulation, biochemical profile, hormonal profile and clinical symptoms of hyperandrogenism were evaluated before and after 6 months of metformin and placebo treatments. We observed a significant decrease in WHR following metformin therapy in the normoinsulinemic overweight sub-group (P < 0.05). The duration of the menstrual cycle significantly decreased in the normoinsulinemic obese sub-group on metformin therapy (P < 0.05). Metformin had a significant effect on hirsutism scores in hyperinsulinemic lean women (P < 0.05) and decreased DHEAS levels significantly in the lean hyperinsulinemic and normoinsulinemic groups (P < 0.05). Metformin had significant effects on ovulation in only lean hyperinsulinemic women (P < 0.05). Clinical outcomes of metformin therapy may be categorized on the basis of basal BMI and insulin levels in PCOS patients.

Dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS) compared with women with non-PCOS-related infertility.

PubMed

Tsai, Ya-Hui; Wang, Ting-Wen; Wei, Hsiao-Jui; Hsu, Chien-Yeh; Ho, Hsin-Jung; Chen, Wen-Hua; Young, Robert; Liaw, Chian-Mey; Chao, Jane C-J

2013-06-28

The present study investigated dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS). A total of forty-five women (aged 25–40 years) with PCOS and 161 control women (aged 25–43 years) with non-PCOS-related infertility were recruited. Anthropometry, glucose tolerance and sex hormones were determined and dietary intake was assessed. Women with PCOS had lower serum sex hormone-binding globulin and increased BMI, waist:hip ratio, luteinising hormone, ratio of luteinising hormone: follicle-stimulating hormone, testosterone and free androgen index (FAI). Postprandial glucose, fasting insulin and insulin resistance were elevated in women with PCOS. Women with PCOS had reduced energy and carbohydrate intake but higher fat intake. Serum sex hormone-binding globulin level was negatively associated with BMI in both groups and negatively correlated with macronutrient intake in the PCOS group with hyperandrogenism. However, FAI was positively correlated with BMI, waist circumference and glucose metabolic parameters in both groups. Therefore, women with PCOS consume lower energy and carbohydrate compared with those with non-PCOS-related infertility and macronutrient intake is only negatively associated with serum sex hormone-binding globulin level in the PCOS group with hyperandrogenism.

Vitamin D is independently associated with depression in overweight women with and without PCOS.

PubMed

Moran, L J; Teede, H J; Vincent, A J

2015-03-01

Depression, anxiety, and inflammation are common in polycystic ovary syndrome (PCOS). Inflammation may adversely impact on mood and vitamin D has been associated with both mood disorders and inflammation in the general population, but these relationships have not been studied in PCOS. The aim of this study was to investigate the association among 25 hydroxy-Vitamin D (25OHVD) status, anxiety, depression, and inflammation in women with and without PCOS. Cross-sectional study in overweight or obese premenopausal women with (n = 50) and without (n = 23) PCOS. Primary outcome measures were 25OHVD, mood (Hospital Anxiety and Depression questionnaire), and inflammation (highly sensitive C-reactive protein (hsCRP)). Vitamin D deficiency (25OHVD<50 nmol/L) (46% versus 39%, p = 0.311) and 25OHVD (50.4 ± 22.2 nmol/L versus 51.6 ± 19.0 nmol/L, p = 0.828) were not significantly different in women with and without PCOS. For all women combined, 25OHVD was the only significant independent predictor of depression (β = -0.063 ± 0.021, p = 0.005) and hsCRP (β = -0.041 ± 0.015, p = 0.010). Vitamin D deficiency is common in both women with and without PCOS with no differences between the groups. Vitamin D is independently associated with depression and inflammation in overweight women both with and without PCOS. Further investigation to clarify the interrelationship among vitamin D, inflammation and depression is required to identify optimal prevention and treatment strategies for psychological and metabolic dysfunction in PCOS.

Do South Asian women with PCOS have poorer health-related quality of life than Caucasian women with PCOS? A comparative cross-sectional study.

PubMed

Jones, Georgina L; Palep-Singh, Manisha; Ledger, William L; Balen, Adam H; Jenkinson, Crispin; Campbell, Michael J; Lashen, Hany

2010-12-20

Polycystic ovary syndrome (PCOS) is the most common chronic endocrine disorder affecting women of reproductive age. This study aimed to compare the HRQoL of South Asian and white Caucasian women with PCOS, given that it is particularly common among women of South Asian origin and they have been shown to have more severe symptoms. The Polycystic Ovary Syndrome Questionnaire (PCOSQ) and the Short Form-36 (SF-36) were administered in a cross-sectional survey to 42 South Asian and 129 Caucasian women diagnosed with PCOS recruited from the gynaecology outpatient clinics of two university teaching hospitals in Sheffield and Leeds. Additional clinical data was abstracted from medical notes. Normative data, collected as part of the Oxford Health and Lifestyles II survey, was obtained to compare SF-36 results with ethnically matched women from the general UK population. Using the SF-36, normative HRQoL scores for women of South Asian origin were lower than for Caucasian women. Given this lower baseline we tested whether the same relationship holds true among those with PCOS. Although HRQoL scores for women with PCOS were lower than normative data for both groups, South Asian women with PCOS did not have poorer HRQoL than their Caucasian counterparts. For both the SF-36 and PCOSQ, mean scores were broadly the same for both Asian and Caucasian women. For both groups, the worst two HRQoL domains as measured on the PCOSQ were 'infertility' and 'weight', with respective scores of 35.3 and 42.3 for Asian women with PCOS compared to 38.6 and 35.4 for Caucasian women with PCOS. The highest scoring domain for South Asian women with PCOS was 'menstrual problems' (55.3), indicating best health, and was the only statistically significant difference from Caucasian women (p = 0.01). On the SF-36, the lowest scoring domain was 'Energy & Vitality' for Caucasian women with PCOS, but this was significantly higher for Asian women with PCOS (p = 0.01). The best health status for both groups

Changes in the PCOS phenotype with age.

PubMed

Hsu, Ming-I

2013-08-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women. The diagnosis of PCOS is mainly based on the following three components: (1) hyperandrogenism, (2) oligo-amenorrhea, and (3) the observation of polycystic ovaries on a sonogram. The comorbidities may include insulin resistance, type II diabetes mellitus, hypertension and cardiovascular disease. Importantly, the diagnostic criteria and complications related to PCOS are age-dependent. Androgen production in women may decrease because of ovarian aging or decreased production by the adrenal glands over time. The prevalence of hirsutism and acne decreases with age. Ovarian volume and follicle number also decrease with age, with the age-related decrease in follicle number seemingly greater than that of ovarian volume. Aging may also be associated with increased risk of insulin resistance and metabolic disturbances. Therefore, these age-related changes may affect the observed incidence and complications of PCOS. In adolescent patients, the criteria described above pose particular diagnostic problems because the characteristics of normal puberty often overlap with the signs and symptoms of PCOS. Hyperandrogenism and chronic anovulation are the primary disturbances in younger women with PCOS; whereas, obesity, insulin resistance, and metabolic disturbances are predominant in older women with PCOS. The deterioration of insulin resistance during the reproductive life of women with PCOS appears to be mainly attributable to the increase in obesity. Therefore, if body weight could be controlled properly, younger hyperandrogenic PCOS women might reduce their risk of insulin resistance and metabolic disturbances later in life. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of orlistat vs. metformin on weight loss-related clinical variables in women with PCOS: systematic review and meta-analysis.

PubMed

Graff, S K; Mario, F M; Ziegelmann, P; Spritzer, P M

2016-06-01

The aim of this study was to assess the effects of orlistat on weight loss-related clinical variables in overweight/obese women with polycystic ovary syndrome (PCOS) and to compare treatment with orlistat vs. metformin in this group. We conducted a systematic review and meta-analysis of the evidence about the use of orlistat in women with PCOS. We searched the literature published until May 2015 in MEDLINE, Cochrane Central Register of Controlled Trials and LILACS. Of 3951 studies identified, nine were included in the systematic review (three prospective, non-randomised studies and six randomised control trials). Eight studies used the Rotterdam criteria and 1 used NIH criteria to diagnose PCOS. Data suggest that orlistat promotes a significant reduction in BMI/weight in overweight/obese PCOS women. Eight studies evaluated orlistat impact on testosterone. Seven reported an improvement in testosterone levels. Eight studies evaluated impact on insulin resistance, and five reported improvement. Finally, five studies evaluated impact on lipid profile, and four reported improvement. Three randomised control trials were included in the fixed effects model meta-analysis for a total of 121 women with PCOS. Orlistat and metformin had similar positive effects on BMI (-0.65%, 95% CI: -2.03 to 0.73), HOMA (-3.60%, 95% CI: -16.99 to 9.78), testosterone (-2.08%, 95% CI: -13.08 to 8.93) and insulin (-5.51%, 95% CI: -22.27 to 11.26). The present results suggest that orlistat leads to significant reduction in BMI/body weight in PCOS. In addition, the available evidence indicates that orlistat and metformin have similar effects in reducing BMI, HOMA, testosterone and insulin in overweight/obese PCOS women. This study was registered in PROSPERO under number CRD42014012877. © 2016 John Wiley & Sons Ltd.

Reproductive health, obesity, and cardiometabolic risk factors among Samoan women.

PubMed

Maredia, H; Hawley, N L; Lambert-Messerlian, G; Fidow, U; Reupena, M S; Naseri, T; McGarvey, S T

2018-04-16

Obesity leads to deleterious effects on not only cardiovascular health but also on the reproductive health of women. We estimate the prevalence of menstrual irregularity and of polycystic ovarian syndrome (PCOS) in Samoan women, among whom obesity prevalence is extremely high. We explore the association of these reproductive health conditions with adiposity, cardiometabolic risk factors, and androgen levels. A cross-sectional sample of Samoan women 25-39 years of age (n = 470) from a larger population-based genome-wide association study of adiposity and cardiometabolic disease was assessed for the prevalence of oligomenorrhea/amenorrhea (OM/AM) using a self-reported questionnaire. Serum androgens and anti-Müllerian hormone levels were assayed to determine hyperandrogenemia and presence of polycystic ovaries (PCO), respectively, using criterion values. PCOS was classified using NIH guidelines of having at least two of the three conditions: menstrual irregularity, hyperandrogenism, and PCO. We contrasted socio-demographic, reproductive health, and cardiometabolic risk factors between those with and without OM/AM and similarly for PCOS. The prevalence of OM/AM was 7.4% (95% CI: 5.1, 9.8), and women with OM/AM had significantly higher central adiposity. PCOS was estimated at 6.8% (95% CI: 4.5, 9.1), and those with PCOS were younger but had higher overall and central adiposity measures, higher triglycerides, and higher prevalence of insulin resistance than women without PCOS. The prevalence of menstrual irregularity and PCOS are less than hypothesized given the high levels of adiposity in this population. Nevertheless, Samoan women with menstrual irregularity and other features of PCOS have significantly poorer metabolic health. © 2018 Wiley Periodicals, Inc.

Diet composition and physical activity in overweight and obese premenopausal women with or without polycystic ovary syndrome.

PubMed

Álvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2011-12-01

The polycystic ovary syndrome (PCOS) is a complex polygenic disorder in which environmental factors play an important modifying role. We aimed to find differences in diet and life-style that might contribute to the development of PCOS among overweight or obese premenopausal women. We compared diet composition and self-reported physical activity among 22 patients with PCOS and 59 women without androgen excess recruited from a total of 113 consecutive premenopausal women reporting for management of weight excess. After correcting for a difference in age between women with PCOS and controls, there were no overall statistical significant differences between them in the total caloric intake, in the intake of macro- and micro-nutrients, caffeine, fiber and alcohol, in the proportion of women exercising regularly, or in the number of hours of exercise per week. The proportion of fat in the diets of the overweight and obese women irrespective of PCOS was well-above current recommendations, yet this excessive fat intake occurred at the expense of monounsaturated fatty acids mostly. In conclusion, diet composition and physical activity were apparently not decisive for the development of PCOS among overweight and obese premenopausal women.

The association between Polycystic Ovary Syndrome (PCOS) and metabolic syndrome: a statistical modelling approach.

PubMed

Ranasinha, S; Joham, A E; Norman, R J; Shaw, J E; Zoungas, S; Boyle, J; Moran, L; Teede, H J

2015-12-01

Polycystic ovary syndrome (PCOS) affects 12-21% of women. Women with PCOS exhibit clustering of metabolic features. We applied rigorous statistical methods to further understand the interplay between PCOS and metabolic features including insulin resistance, obesity and androgen status. Retrospective cross-sectional analysis. Women with PCOS attending reproductive endocrine clinics in South Australia for the treatment of PCOS (n = 172). Women without PCOS (controls) in the same Australian region (n = 335) from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a national population-based study (age- and BMI-matched within one standard deviation of the PCOS cohort). The factor structure for metabolic syndrome for women with PCOS and control groups was examined, specifically, the contribution of individual factors to metabolic syndrome and the association of hyperandrogenism with other metabolic factors. Women with PCOS demonstrated clustering of metabolic features that was not observed in the control group. Metabolic syndrome in the PCOS cohort was strongly represented by obesity (standardized factor loading = 0·95, P < 0·001) and insulin resistance factors (loading = 0·92, P < 0·001) and moderately by blood pressure (loading = 0·62, P < 0·001) and lipid factors (loading = 0·67, P = 0·002). On further analysis, the insulin resistance factor strongly correlated with the obesity (r = 0·70, P < 0·001) and lipid factors (r = 0·68, P < 0·001) and moderately with the blood pressure factor (loading = 0·43, P = 0·002). The hyperandrogenism factor was moderately correlated with the insulin resistance factor (r = 0·38, P < 0·003), but did not correlate with any other metabolic factors. PCOS women are more likely to display metabolic clustering in comparison with age- and BMI-matched control women. Obesity and insulin resistance, but not androgens, are independently and most strongly associated with metabolic syndrome in PCOS. © 2015 John Wiley

Longterm management of Polycystic Ovarian Syndrome (PCOS).

PubMed

Bates, Gordon W; Legro, Richard S

2013-07-05

Polycystic Ovarian Syndrome (PCOS) has been associated with numerous reproductive and metabolic abnormalities. Despite tremendous advances in the management of reproductive dysfunction, insight into the metabolic implications of PCOS is limited by the lack of uniform diagnostic criteria, the heterogeneity of the condition and the presence of confounders including obesity. Obesity clearly has a role in long term health and may best predict both reproductive and metabolic dysfunction as well as negatively affect the response to treatment in women with PCOS. Diabetes, cardiovascular disease and cancer are also at the forefront of any risk assessment or comprehensive treatment strategy for these women. Lifestyle modifications including dietary changes, increased exercise and weight loss are appropriate first line interventions for many women with PCOS. Pharmaceuticals including metformin, lipid lowering agents and oral contraceptives should be tailored to the individual's risk profile and treatment goals. Copyright © 2012. Published by Elsevier Ireland Ltd.

Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS.

PubMed

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N; Dokras, Anuja

2014-05-01

particles (P < .01). Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.

Decreased Cholesterol Efflux Capacity and Atherogenic Lipid Profile in Young Women With PCOS

PubMed Central

Roe, Andrea; Hillman, Jennifer; Butts, Samantha; Smith, Mathew; Rader, Daniel; Playford, Martin; Mehta, Nehal N.

2014-01-01

-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01). Conclusions: Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population. PMID:24512495

Assessment of insulin resistance in Chinese PCOS patients with normal glucose tolerance.

PubMed

Gao, Jing; Zhou, Li; Hong, Jie; Chen, Chen

2017-11-01

The study aimed to investigate insulin resistance (IR) status in polycystic ovary syndrome (PCOS) women with normal glucose tolerance (NGT), and further to evaluate feasible diagnostic method for those patients. Three hundred and twenty-five PCOS women with NGT and ninety-five healthy age-matched controls were recruited with Rotterdam criterion and 75 g oral glucose tolerance test (OGTT). IR status was estimated following a glycemic and insulinemic OGTT (0, 30, 60, 120, and 180 min). A modified HOMA-IR formula was applied to each time-course value of glycemia and insulinemia. The predictive performance of each IR index was analyzed with the use of ROC curves. Compared with healthy controls, both non-obese and obese PCOS patients with NGT had a higher BMI, serum glucose, insulin value (p < .05). The best predictive index of IR in non-obese PCOS-NGT was a HOMA-M30 value of 20.36 or more (AUC: 0.753). In obese PCOS-NGT population, the best predictive performance was obtained by a HOMA-M60 value of 32.17 or more (AUC: 0.868). IR was common in Chinese PCOS women with NGT, and the early assessment of IR should be heeded. We recommended HOMA-M30 (Cutoff: 20.36) and HOMA-M60 (Cutoff: 32.17) as the best predictive parameters for non-obese and obese PCOS-NGT patients, respectively.

Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome.

PubMed

Seow, Kok-Min; Juan, Chi-Chang; Ho, Low-Tone; Hsu, Yung-Pei; Lin, Yu-Hung; Huang, Lee-Wen; Hwang, Jiann-Loung

2007-04-01

The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.

Subclinical hypothyroidism is not a risk factor for polycystic ovary syndrome in obese women of reproductive age.

PubMed

Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Gu, Tianwei; Zhu, Dalong; Bi, Yan

2018-04-16

Obese women are at high risk for polycystic ovary syndrome (PCOS). Subclinical hypothyroidism (SCH) has been associated with weight gain, insulin resistance and impaired fertility, which are also factors involved in PCOS. However, there is limited information regarding the influence of SCH on the presence of PCOS. In order to determine whether SCH increases the prevalence of PCOS, we performed a cross-sectional study in a cohort of reproductive-aged obese women. All subjects underwent anthropometric evaluation, laboratory tests and ultrasound examination. Diagnosis of PCOS was based on the Rotterdam criteria. A total of 534 obese women were included and 108 (20.2%) of them were diagnosed with SCH. Patients with SCH showed similar insulin resistance, comparable androgen levels, and higher triglycerides levels (1.7 vs. 1.5 mmol/L, p = .002) compared to those with normal thyroid status. The frequency of PCOS did not differ between the two groups (56.1% for normal thyroid function vs. 60.2% for subclinical hypothyroidism, p = .514). In logistic regression analysis, SCH was not an independent risk factor for PCOS after adjusting for confounding factors (OR = 0.984, 95% CI 0.581-1.667). For the first time, our results suggest that SCH does not increase the risk of PCOS in obese women of reproductive age.

The prevalence of Type 2 diabetes is not increased in normal-weight women with PCOS.

PubMed

Pelanis, Rasa; Mellembakken, Jan Roar; Sundström-Poromaa, Inger; Ravn, Pernille; Morin-Papunen, Laure; Tapanainen, Juha S; Piltonen, Terhi; Puurunen, Johanna; Hirschberg, Angelica Lindén; Fedorcsak, Peter; Andersen, Marianne; Glintborg, Dorte

2017-11-01

Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? OGTT is not routinely needed in women with PCOS and BMI < 25 kg/m2. PCOS is associated with insulin resistance and increased prevalence of prediabetes and Type 2 diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and during follow-up. A Nordic cross-sectional study including 876 women. The 876 Nordic women with PCOS, aged 14-57 years, were examined for T2D and prediabetes (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. Of all study subjects 3% (23/876) had T2D, 23% (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT). Increased BMI and waist circumference were significantly (P < 0.001) associated with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m2) was diagnosed with T2D. The prevalence of BMI ≥ 25 kg/m2 was 66% (578/ 876). 91% of women (21/23) with T2D had BMI ≥ 30 kg/m2. Testosterone levels and PCOS phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI and age. The present study included cross-sectional data and prospective studies are needed to confirm our results. These results may not apply to populations of other ethnic origin. Routine OGTT may not be indicated in normal-weight women with PCOS. None. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome.

PubMed

Yang, Jehn-Hsiahn; Chou, Chia-Hung; Yang, Wei-Shiung; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2015-12-01

Obesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. One hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. Ferritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p < 0.0001) than nonobese women with PCOS. Using univariate analysis, the AMH level and mean ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. An elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS. Copyright © 2015. Published by Elsevier B.V.

Hepatic Steatosis is Common in Adolescents with Obesity and PCOS and Relates to De Novo Lipogenesis but Insulin Resistance

PubMed Central

Cree-Green, M.; Bergman, B. C.; Coe, G. V.; Newnes, L.; Baumgartner, A.D.; Bacon, S.; Sherzinger, A.; Pyle, L.; Nadeau, K. J.

2016-01-01

Objective Increased liver fat and type 2 diabetes are prevalent in women with polycystic ovarian syndrome (PCOS) and cause excess mortality, yet little is known about their development during adolescence. Our goal was to measure hepatic steatosis and related metabolic contributors in girls with obesity, with and without PCOS. Methods Nondiabetic adolescents with obesity, 41 with PCOS (PCOS; age 15.0(13.0,16.0) years, BMI 35.2±0.61 kg/m2) and 30 without PCOS (OB; age 14.5(13.0,17.0), BMI 33.2±1.8) were studied. Visceral and liver fat were assessed with MRI. Serum measures included androgens and 16 and 18 n7 fatty acids specific to de novo lipogenesis. Adipose, hepatic and peripheral insulin sensitivity (IS) were assessed with a 4-phase hyperinsulinemic-euglycemic clamp with isotope tracers. Results 49% PCOS had hepatic steatosis vs. 14% OB (p=0.02), and PCOS had higher n7 (43±4 nmol/g vs. 29±5; p=0.02). Peripheral IS was lower in PCOS (9.4(7.2,12.3) mg/lean kg/min vs. 14.5(13.1,18.05); p<0.001) as was hepatic (p=0.006) and adipose IS (p=0.005). Percent liver fat correlated with n7 (R=0.46, p=0.02) and visceral fat (R=0.42, p<0.001), not androgens or peripheral IS. Conclusions Nearly 50% of nondiabetic girls with PCOS and obesity have hepatic steatosis, which related to visceral fat and lipogenesis, but not to IS or androgens. PMID:27804265

National survey on management of weight reduction in PCOS women in the United Kingdom.

PubMed

Sharma, Aarti; Walker, Dawn-Marie; Atiomo, William

2010-10-01

To identify the most commonly used methods for weight reduction in women with polycystic ovarian syndrome (PCOS) utilized by obstetricians and gynaecologists in the United Kingdom (UK). Permission was sought from the Royal College of Obstetricians and Gynaecologists (RCOG) to conduct an electronic survey of all consultants practising in the UK. The questionnaire was anonymous and an electronic link was sent via email to the 1140 consultants whose details were provided by the RCOG. A 27-item questionnaire was developed. The variables evaluated were first-line methods of weight reduction used, proportion of women with PCOS seen that were obese, whether the patients had tried other weight reduction methods before seeking help, the optimal dietary advice and optimal composition, the optimal duration and frequency of exercise suggested, BMI used for suggesting weight loss, percentage of women in whom weight loss worked, length of time allowed prior to suggesting another method, methods considered most effective by patients, use of metformin for weight loss, criteria used for prescribing metformin, first-line anti-obesity drugs preferred if any, second- and third-line methods used, referral to other specialists and criteria for referral for bariatric surgery. Responses were categorical and are reported as proportions. One hundred and seven (9.4%) consultants responded to the questionnaire. One hundred and four (97%) provided advice on diet and 101 (94%) advice on exercise as their first-line strategy for weight management. Fifty-one (47.7%) stated that they provided specific information on an optimal dietary intake, 53 (49.9%) on the optimal dietary composition and 61 (57%) on the optimal duration and frequency of exercise per week. The commonest second-line methods used were anti-obesity drugs and metformin and the most popular third-line management options were anti-obesity drugs and bariatric surgery. The results suggest that the information provided to women with

Correlations Between Anthropometry and Lipid Profile in Women With PCOS.

PubMed

Kiranmayee, Donthu; Kavya, Kothapalli; Himabindu, Yalamanchali; Sriharibabu, Manne; Madhuri, Gadi Leela Jaya; Venu, Swargam

2017-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women and is associated with both reproductive and metabolic abnormalities. Recent studies have demonstrated an early onset of abnormal cardiovascular risk profile in women with PCOS. Abnormal lipid profile patterns are common in women with PCOS, and these abnormalities are not uniform in all populations. Anthropometry is a simple and commonly used research tool for assessing metabolic risk in women with PCOS. Therefore, this study examined the correlations between anthropometric parameters and lipid profile in women with PCOS. The objectives of the study were (1) To study the anthropometric profile of women with PCOS, (2) To examine the lipid profile pattern of these women with PCOS and (3) To see whether there exists any correlation between these anthropometric parameters and lipid profile. This observational cross-sectional study examined anthropometry and lipid profile in 86 married women with PCOS in the age group of 18-35 years and correlated them by using Pearson's correlation coefficient. More than 80% of the women with PCOS demonstrated abnormal anthropometric parameters, and in more than 70% women, lipid abnormalities such as low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides and low-density lipoprotein cholesterol were observed. Significant positive correlations were seen between body mass index (BMI) and triglycerides ( P ≤ 0.001) and waist circumference (WC) and triglycerides ( P ≤ 0.029). Negative correlations were observed between BMI and HDL cholesterol ( P ≤ 0.013). This study revealed that BMI and WC are the most important anthropometric parameters correlated to dyslipidemia in the south Indian women with PCOS.

[Polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women].

PubMed

Orio, Francesco; Cascella, Teresa; Giallauria, Francesco; Palomba, Stefano; De Lorenzo, Anna; Lucci, Rosa; Ambrosino, Elena; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo

2006-03-01

Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

PubMed

Ganie, Mohd Ashraf; Marwaha, Raman Kumar; Dhingra, Atul; Nisar, Sobia; Mani, Kaliavani; Masoodi, Shariq; Chakraborty, Semanti; Rashid, Aafia

2016-07-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.

Clitoral and labial sizes in women wıth PCOS.

PubMed

Köşüş, A; Kamalak, Z; Köşüş, N; Hizli, D; Eser, A

2016-01-01

The aim of this study was to examine the external genital features in Turkish women with polycystic ovary syndrome (PCOS). Thirty-two newly diagnosed PCOS cases and 35 healthy women were included the study. All women underwent a thorough gynaecological examination. Clitoral length, and labia minora length and width were recorded. The groups were compared for features of external genital structures. Clitoral and labial lengths were significantly higher in PCOS group. There was a strong correlation between clitoral length and modified Ferriman-Gallwey score. The most effective predictor of PCOS was found to be clitoral length. Clitoral length alone predicted 99.9% of PCOS patients. There were some subclinical genital changes in women with PCOS. These changes in PCOS patients may be a sign of hyperandrogenism and might have diagnostic value in indistinct cases.

DHEA, DHEAS and PCOS.

PubMed

Goodarzi, Mark O; Carmina, Enrico; Azziz, Ricardo

2015-01-01

Approximately 20-30% of PCOS women demonstrate excess adrenal precursor androgen (APA) production, primarily using DHEAS as a marker of APA in general and more specifically DHEA, synthesis. The role of APA excess in determining or causing PCOS is unclear, although observations in patients with inherited APA excess (e.g., patients with 21-hydroxylase deficient congenital classic or non-classic adrenal hyperplasia) demonstrate that APA excess can result in a PCOS-like phenotype. Inherited defects of the enzymes responsible for steroid biosynthesis, or defects in cortisol metabolism, account for only a very small fraction of women suffering from hyperandrogenism or APA excess. Rather, women with PCOS and APA excess appear to have a generalized exaggeration in adrenal steroidogenesis in response to ACTH stimulation, although they do not have an overt hypothalamic-pituitary-adrenal axis dysfunction. In general, extra-adrenal factors, including obesity, insulin and glucose levels, and ovarian secretions, play a limited role in the increased APA production observed in PCOS. Substantial heritabilities of APAs, particularly DHEAS, have been found in the general population and in women with PCOS; however, the handful of SNPs discovered to date account only for a small portion of the inheritance of these traits. Paradoxically, and as in men, elevated levels of DHEAS appear to be protective against cardiovascular risk in women, although the role of DHEAS in modulating this risk in women with PCOS remains unknown. In summary, the exact cause of APA excess in PCOS remains unclear, although it may reflect a generalized and inherited exaggeration in androgen biosynthesis of an inherited nature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adrenal hyperandrogenism does not deteriorate insulin resistance and lipid profile in women with PCOS.

PubMed

Paschou, Stavroula A; Palioura, Eleni; Ioannidis, Dimitrios; Anagnostis, Panagiotis; Panagiotakou, Argyro; Loi, Vasiliki; Karageorgos, Georgios; Goulis, Dimitrios G; Vryonidou, Andromachi

2017-11-01

The aim of this study was to investigate the impact of adrenal hyperandrogenism on insulin resistance and lipid profile in women with polycystic ovary syndrome (PCOS). We studied 372 women with PCOS according to the NIH criteria. 232 age- and BMI-matched women served as controls in order to define adrenal hyperandrogenism (DHEA-S >95th percentile). Then, patients with PCOS were classified into two groups: with adrenal hyperandrogenism (PCOS-AH, n  = 108) and without adrenal hyperandrogenism (PCOS-NAH, n  = 264). Anthropometric measurements were recorded. Fasting plasma glucose, insulin, lipid profile, sex hormone-binding globulin (SHBG) and androgen (TT, Δ4A, DHEA-S) concentrations were assessed. Free androgen index (FAI) and homeostatic model assessment-insulin resistance (HOMA-IR) index were calculated. Women with PCOS-AH were younger than PCOS-NAH ( P  < 0.001), but did not differ in the degree and type of obesity. No differences were found in HOMA-IR, total cholesterol, HDL-c, LDL-c and triglyceride concentrations (in all comparisons, P  > 0.05). These metabolic parameters did not differ between the two groups even after correction for age. Women with PCOS-AH had lower SHBG (29.2 ± 13.8 vs 32.4 ± 11.8 nmol/L, P  = 0.025) and higher TT (1.0 ± 0.2 vs 0.8 ± 0.4 ng/mL, P  = 0.05) and Δ4A (3.9 ± 1.2 vs 3.4 ± 1.0 ng/mL, P  = 0.007) concentrations, as well as FAI (14.1 ± 8.0 vs 10.2 ± 5.0, P  < 0.001). These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age ( P  < 0.001) and SHBG concentrations ( P  = 0.02), but not with any metabolic parameter. Women with PCOS and adrenal hyperandrogenism do not exhibit any deterioration in insulin resistance and lipid profile despite the higher degree of total androgens. © 2017 The authors.

Epidemiologic investigation of polycystic ovarian syndrome (PCOS) in Han ethnic women of reproductive age in Liaoning Province, China.

PubMed

Jiao, J; Fang, Y; Wang, T; Wang, Z; Zhou, M; Wang, X

2014-01-01

To determine the incidence of polycystic ovary syndrome (PCOS) among Han women of reproductive age in Liaoning Province in Northeastern China, based on the Revised Rotterdam 2003 criteria. A retrospective cohort study was carried out on 1,600 women using questionnaires, physical examination, ultrasonography, and biochemical indices (aged = 19 to 45 years; n = 1,600). PCOS patients were identified using the Revised Rotterdam 2003 criteria. A total of 132 Han women of reproductive age were diagnosed with PCOS, with a prevalence of 8.25%. The prevalence of menstrual dysfunction was as follows: 97 patients (73.48%) had abnormal menstruation, three (2.27%) had polymenorrhea, and 94 (71.21%) had oligomenorrhea. Up to 64 patients (48.48%) had androgen excess, 42 (31.82%) had biochemical evidence of androgen excess, and 34 (25.76%) had clinical androgen excess. Up to 34 patients (25.76%) were obese (body mass index [BMI] > or = 25) and 19 (14.39%) had hirsutism (F-G scoring > or = 6). A total of 127 patients (96.22%) were diagnosed with PCOS via ultrasonography, 67 of whom (50.76%) had a unilateral polycystic ovary and 60 (45.46%) had bilateral polycystic ovaries. The prevalence of PCOS in this study population was 8.25%, with an infertility rate of 27.8%. The classical manifestation of PCOS is PCO, abnormal menstruation, and obesity. The high-risk factors of PCOS include high free testosterone index, homeostasis model assessment-insulin resistance (HOMA-IR), increased serum testosterone and androstenedione, decreased sex hormone-binding globulin, long history of infertility, menarche later than 16 years old, and failure to have regular menstruation within two years.

Hepatic Steatosis is Common in Adolescents with Obesity and PCOS and Relates to De Novo Lipogenesis but not Insulin Resistance.

PubMed

Cree-Green, Melanie; Bergman, Bryan C; Coe, Gregory V; Newnes, Lindsey; Baumgartner, Amy D; Bacon, Samantha; Sherzinger, Ann; Pyle, Laura; Nadeau, Kristen J

2016-11-01

Increased liver fat and type 2 diabetes are prevalent in women with polycystic ovarian syndrome (PCOS) and cause excess mortality, yet little is known about their development during adolescence. The objective of this study was to measure hepatic steatosis and related metabolic contributors in girls with obesity, with and without PCOS. Nondiabetic adolescents with obesity, 41 with PCOS (PCOS; age 15.0 [13.0-16.0] years, BMI 35.2 ± 0.61 kg/m 2 ) and 30 without PCOS (OB; age 14.5 [13.0-17.0], BMI 33.2 ± 1.8), were studied. Visceral and liver fat were assessed with MRI. Serum measures included androgens and 16:1 and 18:1 N7 fatty acids specific to de novo lipogenesis. Adipose, hepatic, and peripheral insulin sensitivity (IS) were assessed with a four-phase hyperinsulinemic-euglycemic clamp with isotope tracers. Forty-nine percent of the PCOS group had hepatic steatosis versus fourteen percent of the OB group (P = 0.02), and the PCOS group had higher N7 (43 ± 4 vs. 29 ± 5 nmol/g; P = 0.02). Peripheral IS was lower in PCOS (9.4 [7.2-12.3] vs. 14.5 [13.1-18.05 mg/lean kg/min]; P < 0.001) as was hepatic (P = 0.006) and adipose IS (P = 0.005). Percent liver fat correlated with N7 (R = 0.46, P = 0.02) and visceral fat (R = 0.42, P < 0.001), not androgens or peripheral IS. Nearly 50% of nondiabetic girls with PCOS and obesity have hepatic steatosis, which relates to visceral fat and lipogenesis, but not to IS or androgens. © 2016 The Obesity Society.

Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression.

PubMed

Kakoly, N S; Khomami, M B; Joham, A E; Cooray, S D; Misso, M L; Norman, R J; Harrison, C L; Ranasinha, S; Teede, H J; Moran, L J

2018-03-26

Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for

Phenotype and metabolic profile of South Asian women with polycystic ovary syndrome (PCOS): results of a large database from a specialist Endocrine Clinic.

PubMed

Wijeyaratne, Chandrika N; Seneviratne, Ruwanthi de A; Dahanayake, Shamalka; Kumarapeli, Vindya; Palipane, Ethusha; Kuruppu, Nadeera; Yapa, Chandrika; Seneviratne, Rohini de A; Balen, Adam H

2011-01-01

Compared with other populations, South Asians have a greater propensity to insulin resistance and the metabolic syndrome (MetS). This is the first study to determine the distribution of phenotypes of polycystic ovary syndrome (PCOS) and their relationship to the MetS among indigenous South Asians. An evaluation of the phenotype and metabolic characteristics of PCOS was conducted by recruiting consecutive women diagnosed by Rotterdam consensus criteria from an Endocrine clinic in Colombo, Sri Lanka. Prevalence of MetS was determined, in relation to the phenotypic subgroup of PCOS and compared with ethnically matched, BMI- and age-adjusted controls (n =231). Acanthosis nigricans (AN) occurred in 64.6% of women with PCOS (n= 469). MetS occurred in 30.6% of the PCOS group compared with 6.34% of controls (P = 0.0001). Those with PCOS and MetS had significantly higher median BMI, blood pressure (BP), fasting plasma glucose, insulin and triglycerides and lower high-density lipoprotein and sex hormone-binding globulin (SHBG), but similar testosterone concentrations compared with those with PCOS alone. Prevalence of MetS was similar in the four PCOS phenotypes, although oligomenorrhoeic women were more obese compared with the normal cycling hyperandrogenic group. Multivariate logistic regression confirmed age ≥35 years, BMI ≥25 kg/m(2) and AN as significant predictors of MetS in PCOS. Case-control comparisons showed that the presence of PCOS results in higher odds of having the MetS, a high waist circumference, elevated diastolic BP, abnormal fasting lipids and high fasting insulin and plasma testosterone concentrations. Young indigenous South Asians with PCOS have greater odds of being centrally obese, with a third having the MetS that bears no relationship to the androgenic phenotype. Significant predictors for MetS within the PCOS cohort are advancing age, obesity determined by the Asian cut off (BMI >25 kg/m(2)) and AN, while family history of diabetes

Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS.

PubMed

Kandaraki, Eleni; Chatzigeorgiou, Antonis; Livadas, Sarantis; Palioura, Eleni; Economou, Frangiscos; Koutsilieris, Michael; Palimeri, Sotiria; Panidis, Dimitrios; Diamanti-Kandarakis, Evanthia

2011-03-01

Bisphenol A (BPA) is a widespread industrial compound used in the synthesis of polycarbonate plastics. In experimental animals, neonatal exposure to BPA results in a polycystic ovary-like syndrome (PCOS) in adulthood. A bidirectional interaction between androgens and BPA levels has been disclosed. To determine BPA levels in PCOS women as well as the association between BPA and hormonal/metabolic parameters compared to a control group. Cross-sectional study of 71 PCOS (National Institutes of Health criteria) and 100 normal women, age- and body mass index-matched, in a University hospital setting. Anthropometric, hormonal, metabolic parameters and BPA blood levels were determined. Patients (PCOS) and controls (C) were further subdivided according to body mass index into lean and overweight subgroups, respectively. BPA levels were significantly higher in the total PCOS group compared with the controls (1.05±0.56 vs. 0.72±0.37 ng/ml, P < 0.001). PCOS women, lean (PCOS-L) and overweight (PCOS-OW), had higher BPA levels compared to the corresponding control group lean (C-L) and overweight (C-OW): (PCOS-L = 1.13±0.63 vs. C-L = 0.70±0.36, P < 0.001) (PCOS-OW = 0.96 ± 0.46 vs. C-OW = 0.72 ± 0.39, P < 0.05). A significant association of testosterone (r = 0.192, P < 0.05) and androstenedione (r = 0.257, P < 0.05) with BPA was observed. Multiple regression analysis for BPA showed significant correlation with the existence of PCOS (r = 0.497, P < 0.05). BPA was also positively correlated with insulin resistance (Matsuda index) in the PCOS group (r = 0.273, P < 0.05). Higher BPA levels in PCOS women compared to controls and a statistically significant positive association between androgens and BPA point to a potential role of this endocrine disruptor in PCOS pathophysiology.

Cancer risk and PCOS.

PubMed

Dumesic, Daniel A; Lobo, Rogerio A

2013-08-01

Women with polycystic ovary syndrome (PCOS) have a 2.7-fold increased risk for developing endometrial cancer. A major factor for this increased malignancy risk is prolonged exposure of the endometrium to unopposed estrogen that results from anovulation. Additionally, secretory endometrium of some women with PCOS undergoing ovulation induction or receiving exogenous progestin exhibits progesterone resistance accompanied by dysregulation of gene expression controlling steroid action and cell proliferation. Endometrial surveillance includes transvaginal ultrasound and/or endometrial biopsy to assess thickened endometrium, prolonged amenorrhea, unopposed estrogen exposure or abnormal vaginal bleeding. Medical management for abnormal vaginal bleeding or endometrial hyperplasia consists of estrogen-progestin oral contraceptives, cyclic or continuous progestins or a levonorgestrel-releasing (Mirena) intrauterine device. Lifestyle modification with caloric restriction and exercise is appropriate to treat obesity as a concomitant risk factor for developing endometrial disease. An increased risk of ovarian cancer may also exist in some women with PCOS. There are strong data to suggest that oral contraceptive use is protective against ovarian cancer and increases with the duration of therapy. The mechanism of this protection may be through suppression of gonadotropin secretion rather than the prevention of "incessant ovulation". There is no apparent association of PCOS with breast cancer, although the high prevalence of metabolic dysfunction from obesity is a common denominator for both conditions. Recent data suggest that the use of metformin may be protective for both endometrial and breast cancer. There are insufficient data to evaluate any association between PCOS and vaginal, vulvar and cervical cancer or uterine leiomyosarcoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome.

PubMed

Livadas, Sarantis; Kollias, Anastasios; Panidis, Dimitrios; Diamanti-Kandarakis, Evanthia

2014-09-01

Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging. A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR. An outpatient clinic was chosen for the study. A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group. The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated. In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese patients (r: -0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles. Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may

Fetuin-A levels in lean and obese women with polycystic ovary syndrome.

PubMed

Kozakowski, Jarosław; Jeske, Wojciech; Zgliczyński, Wojciech

2014-01-01

The aim of this study was to estimate serum fetuin-A levels in lean and obese women with polycystic ovary syndrome (PCOS) and to find possible relationships between fetuin-A, metabolic factors and androgens in these patients. In 25 lean (18-38 years, BMI 17.5-25.0 kg/m2) and 15 obese women (20-41 years, BMI 28.1-53.2 kg/m2) with PCOS, anthropometric indices and body composition were measured. Fasting serum fetuin-A, adiponectin, leptin, glucose, lipids, hsCRP, insulin, androgens and SHGB levels were estimated. There was no significant difference in serum fetuin-A levels between lean and obese patients: 0.54 ± 0.13 g/L and 0.60 ± 0.14 g/L, respectively. We noted a correlation between BMI and leptin levels (r = 0.88; p < 0.0001) and a nearly significant negative correlation between BMI and adiponectin levels (r = -0.53; p = 0.11) in all subjects. In lean patients, we found a correlation between fetuin-A levels and ALT activity (r = 0.44; p < 0.05). In all participants, fetuin-A correlated directly with DHEA-S levels (r = 0.44; p < 0.03). Serum fetuin-A levels were similar in lean and obese women with PCOS. We found an association between fetuin-A levels and ALT activity in lean patients and between fetuin-A levels and DHEA-S in all women. The role of fetuin-A in the mechanisms of insulin resistance, and its potential impact on androgenic hormones production in women with PCOS, need to be tested in further studies.

[Blood pressure and polycystic ovary syndrome (PCOS)].

PubMed

Kiałka, Marta; Milewicz, Tomasz; Klocek, Marek

2015-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder occurring in women of childbearing age. The literature describes the relationship between PCOS and high blood pressure levels and increased risk of arterial hypertension development, which is an important and strong risk factor for adverse cardiovascular events in the future. Among the main causes of hypertension in PCOS women insulin resistance, hyperandrogenism, greater sympathetic nerve activity and concomitance of obesity are stressed. Because PCOS may contribute to earlier development of hypertension, as well as pre-hypertension, therefore it is advisable to monitor blood pressure systematically, to control known risk factors, and to initiate the treatment of hypertension when the disease occur.

Status of Homocysteine in Polycystic Ovary Syndrome (PCOS).

PubMed

Maleedhu, Priyanka; M, Vijayabhaskar; S S B, Sharma; Kodumuri, Praveen K; Devi D, Vasundhara

2014-02-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age and is estimated to affect 5-10 % of the population. Women with PCOS have a clustering of cardiovascular risk factors, such as obesity, dyslipidemia, impaired glucose tolerance and hypertension. Homocysteine has been recognized recently as a risk factor for cardiovascular diseases. Preliminary investigations suggest that high sensitivity C-reactive protein, homocysteine and adiponectin are abnormal in women with PCOS. The possible determinants of elevated homocysteine concentration are still debated among authors who found significant correlations between homocysteine and insulin resistance or hyperandrogenism. The purpose of this study is to evaluate homocysteine levels in the PCOS population compared with controls. Study group comprised of 142 women with PCOS and 65 healthy non-PCOS controls. Body mass index (BMI), Waist circumference and serum homocysteine were measured in PCOS subjects and age matched controls. Statastical Analysis: All values are expressed as mean α SD. The results obtained are analysed statistically using the unpaired student t-test to evaluate the significance of differences between the mean values. The mean BMI, Waist circumference and serum homocysteine values are significantly increased in PCOS subjects when compared with non PCOS controls. The present study has demonstrated increase in mean serum homocysteine concentrations in women with PCOS.

Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome.

PubMed

Cheang, Kai I; Sistrun, Sakita N; Morel, Kelley S; Nestler, John E

2016-01-01

Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS ( n = 16) and normal ( n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUC DCI-IPG ), AUC insulin , and AUC DCI-IPG /AUC insulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUC DCI-IPG /AUC insulin at baseline and a significant relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (-4.08 kg) and normal women (-4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUC DCI-IPG /AUC insulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome and cardiovascular disease compared with white women with PCOS [corrected].

PubMed

Hillman, Jennifer K; Johnson, Lauren N C; Limaye, Meghana; Feldman, Rebecca A; Sammel, Mary; Dokras, Anuja

2014-02-01

To determine the prevalence of metabolic syndrome (MetSyn) and Framingham cardiovascular disease (CVD) risk in white and black adolescents and adult women with polycystic ovary syndrome (PCOS) compared with controls. Retrospective cohort study. Center for PCOS. Subjects with PCOS with data on race and cardiometabolic risk (n = 519). Controls were age and race matched from the National Health and Nutrition Examination Survey (NHANES) population (1999-2006). None. MetSyn, coronary heart disease risk, and general CVD risk. Black adolescents and young adults with PCOS had an increased prevalence of MetSyn compared with their white counterparts (adolescents relative risk 2.65 [95% confidence interval 1.29-5.4], adults relative risk 1.44 [95% confidence interval 1.21-2.6]). In contrast, there was no difference in risk of MetSyn between black and white adolescents and adult women in the NHANES dataset. After controlling for age and body mass index, black women with PCOS had a significantly increased prevalence of low high-density lipoprotein and high glucose. The general CVD risk was significantly increased in black adults with PCOS. This is the first study to comprehensively demonstrate increased risk of MetSyn in both black adolescents and adult women with PCOS compared with white subjects with PCOS. This racial disparity was not present in the NHANES controls. Longitudinal studies are needed to assess the independent impact of PCOS and race on CVD risk in women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Obesity is the major determinant of the abnormalities in blood pressure found in young women with the polycystic ovary syndrome.

PubMed

Luque-Ramírez, Manuel; Alvarez-Blasco, Francisco; Mendieta-Azcona, Covadonga; Botella-Carretero, José I; Escobar-Morreale, Héctor F

2007-06-01

Obesity and insulin resistance predispose patients with the polycystic ovary syndrome (PCOS) to abnormalities in blood pressure regulation. Our objective was to evaluate the impact of obesity on the blood pressure profiles of PCOS patients. PATIENTS, SETTING, AND DESIGN: Thirty-six PCOS patients and 20 healthy women participated in a case-control study at an academic hospital. We conducted ambulatory blood pressure monitoring and office blood pressure determinations. Hypertension (defined as increased office blood pressure confirmed by ambulatory blood pressure monitoring or by masked hypertension) was present in 12 PCOS patients and eight controls (P = 0.618). No differences between patients and controls were found in office and ambulatory blood pressure monitoring values and heart rate, yet the nocturnal decrease in mean blood pressure was smaller in patients (P = 0.038). Obese women (13 patients and eight controls) had increased frequencies of office hypertension (29% compared with 3% in lean plus overweight women, P = 0.005), increased diastolic (P = 0.009) and mean (P = 0.015) office blood pressure values, and increased heart rate values during the daytime (P = 0.038), nighttime (P = 0.002), and 24-h (P = 0.009) periods, independently of having PCOS or not. The frequency of a nocturnal nondipper pattern was 62% in obese PCOS patients, compared with 26% in lean plus overweight PCOS patients (P = 0.036) and 25% in obese and in lean plus overweight controls. Abnormalities in the regulation of blood pressure are common in young women with PCOS, yet, with the exception of the nondipper pattern, these abnormalities result from the frequent association of this syndrome with obesity.

Mindfulness-Based Stress Reduction for Overweight/Obese Women With and Without Polycystic Ovary Syndrome: Design and Methods of a Pilot Randomized Controlled Trial

PubMed Central

Raja-Khan, Nazia; Agito, Katrina; Shah, Julie; Stetter, Christy M.; Gustafson, Theresa S.; Socolow, Holly; Kunselman, Allen R.; Reibel, Diane K.; Legro, Richard S.

2015-01-01

Mindfulness-based stress reduction (MBSR) may be beneficial for overweight/obese women, including women with polycystic ovary syndrome (PCOS), as it has been shown to reduce psychological distress and improve quality of life in other patient populations. Preliminary studies suggest that MBSR may also have salutary effects on blood pressure and blood glucose. This paper describes the design and methods of an ongoing pilot randomized controlled trial evaluating the feasibility and effects of MBSR in PCOS and non-PCOS women who are overweight or obese. Eighty six (86) women with body mass index ≥25 kg/m2, including 31 women with PCOS, have been randomized to 8 weeks of MBSR or health education control, and followed for 16 weeks. The primary outcome is mindfulness assessed with the Toronto Mindfulness Scale. Secondary outcomes include measures of blood pressure, blood glucose, quality of life, anxiety and depression. Our overall hypothesis is that MBSR will increase mindfulness and ultimately lead to favorable changes in blood pressure, blood glucose, psychological distress and quality of life in PCOS and non-PCOS women. This would support the integration of MBSR with conventional medical treatments to reduce psychological distress, cardiovascular disease and diabetes in PCOS and non-PCOS women who are overweight or obese. PMID:25662105

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Kowalska, Irina; Straczkowski, Marek; Nikolajuk, Agnieszka; Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Otziomek, Elzbieta; Wolczynski, Slawomir; Gorska, Maria

2007-07-01

Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.

Metabolic syndrome and cardiometabolic risk in PCOS.

PubMed

Cussons, Andrea J; Stuckey, Bronwyn G A; Watts, Gerald F

2007-02-01

The cardiovascular risk associated with the polycystic ovary syndrome (PCOS) has recently attracted much interest. Women with PCOS are more likely to fulfill the diagnosis of the metabolic syndrome, a cluster of related cardiometabolic factors known to predict long-term risk of cardiovascular disease and type 2 diabetes. We review the literature pertaining to the link between the metabolic syndrome, cardiovascular disease, and PCOS. We focus on the influence of obesity and hyperandrogenemia, and on strategies for identifying cardiovascular risk in PCOS.

Definition of insulin resistance using the homeostasis model assessment (HOMA-IR) in IVF patients diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria.

PubMed

Alebić, Miro Šimun; Bulum, Tomislav; Stojanović, Nataša; Duvnjak, Lea

2014-11-01

Polycystic ovary syndrome (PCOS) women are more insulin resistant than general population. Prevalence data on insulin resistance (IR) in PCOS vary depending on population characteristics and methodology used. The objectives of this study were to investigate whether IR in PCOS is exclusively associated with body mass and to assess the prevalence of IR in lean and overweight/obese PCOS. Study included 250 consecutive women who attended a Department of Human Reproduction diagnosed as having PCOS according to the Rotterdam criteria. Control group comprised 500 healthy women referred for male factor infertility evaluation during the same period as the PCOS women. PCOS women (n = 250) were more insulin resistant than controls (n = 500) even after adjustment for age and body mass index (BMI) (P = 0.03). Using logistic regression analysis, BMI ≥ 25 kg/m(2) (OR 6.0; 95 % CI 3.3-11.0), PCOS (OR 2.2; 95 % CI 1.4-3.5) and waist circumference ≥ 80 cm (OR 2.0; 95 % CI 1.1-3.8) were identified as independent determinants of IR (P < 0.001). IR was more prevalent in overweight/obese controls (n = 100) than in lean PCOS women (n = 150), 31 versus 9.3 %, but less prevalent than in overweight/obese PCOS (n = 100), 31 versus 57 %. The prevalence of IR between lean controls (5 %) and lean PCOS (9.3 %) did not significantly differ. Both PCOS-specific and obesity-related IR independently contribute to IR in PCOS. Using HOMA-IR cutoff value of 3.15 specific for Croatian women in our clinical setting, the assessed prevalence of IR in lean and overweight/obese PCOS women was 9.3 and 57 %, respectively.

Dissociation of endothelial function and arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS).

PubMed

Cussons, Andrea J; Watts, Gerald F; Stuckey, Bronwyn G A

2009-12-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk but it is not clear if this is independent of obesity and insulin resistance. This study therefore investigates endothelial function and arterial stiffness in nonobese, noninsulin resistant women with PCOS. This is cross-sectional case-control study. A total of 19 young women with PCOS, with body mass index (BMI) <30 kg/m(2), and 19 healthy controls matched for age and BMI were included in the study. Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI). There were no significant differences between PCOS and control subjects when assessing the following clinical and biochemical variables: blood pressure, homeostasis model assessment insulin-resistance index, lipids and oestradiol. Women with PCOS had higher free androgen index scores (5.14 ± 3.47 vs. 3.25 ± 1.42, P = 0.036). The PCOS subjects had significantly lower FMD of the brachial artery compared with the controls (6.5 ± 2.9%vs. 10.5 ± 4.0%, P < 0.01). There were no significant differences in markers of arterial stiffness (PWV 5.8 ± 1.1 vs. 6.0 ± 1.0, P = 0.58, AI 16.5 ± 10.2 vs. 20.3 ± 10.2, P = 0.25). Women with polycystic ovary syndrome who are young, nonobese, and have no biochemical evidence of insulin resistance, have abnormal vascular function, but normal arterial stiffness, when compared with age and weight matched control subjects. Whether this leads to a greater risk of cardiovascular disease requires further investigation. © 2009 Blackwell Publishing Ltd.

Mindfulness-based stress reduction for overweight/obese women with and without polycystic ovary syndrome: design and methods of a pilot randomized controlled trial.

PubMed

Raja-Khan, Nazia; Agito, Katrina; Shah, Julie; Stetter, Christy M; Gustafson, Theresa S; Socolow, Holly; Kunselman, Allen R; Reibel, Diane K; Legro, Richard S

2015-03-01

Mindfulness-based stress reduction (MBSR) may be beneficial for overweight/obese women, including women with polycystic ovary syndrome (PCOS), as it has been shown to reduce psychological distress and improve quality of life in other patient populations. Preliminary studies suggest that MBSR may also have salutary effects on blood pressure and blood glucose. This paper describes the design and methods of an ongoing pilot randomized controlled trial evaluating the feasibility and effects of MBSR in PCOS and non-PCOS women who are overweight or obese (NCT01464398). Eighty six (86) women with body mass index ≥ 25 kg/m(2), including 31 women with PCOS, have been randomized to 8 weeks of MBSR or health education control, and followed for 16 weeks. The primary outcome is mindfulness assessed with the Toronto Mindfulness Scale. Secondary outcomes include measures of blood pressure, blood glucose, quality of life, anxiety and depression. Our overall hypothesis is that MBSR will increase mindfulness and ultimately lead to favorable changes in blood pressure, blood glucose, psychological distress and quality of life in PCOS and non-PCOS women. This would support the integration of MBSR with conventional medical treatments to reduce psychological distress, cardiovascular disease and diabetes in PCOS and non-PCOS women who are overweight or obese. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum AMH levels and insulin resistance in women with PCOS.

PubMed

Sahmay, Sezai; Aydogan Mathyk, Begum; Sofiyeva, Nigar; Atakul, Nil; Azemi, Aslı; Erel, Tamer

2018-05-01

To compare the serum AMH levels between women with and without insulin resistance (IR) in polycystic ovary syndrome (PCOS). 293 women with PCOS according to the Rotterdam criteria were enrolled into our study. Insulin resistance was diagnosed according to the Homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Women were grouped according to the presence of insulin resistance (IR) (HOMA-IR ≥ 2.5). Serum AMH and other hormones were compared between the IR (+) and IR (-) groups. Additionally, AMH percentiles were (<25, 25-75, >75) constructed; HOMA-IR and BMI values in women with/without IR were compared in different percentiles. Further, HOMA-IR, BMI and AMH values were measured across different PCOS phenotypes. The prevalence of IR was 45%. The prevalence of IR was 57% in women with BMI ≥ 25. Serum AMH levels were not significantly different among women with and without IR. Also, HOMA-IR values were not significant among different AMH percentiles. However, in each AMH percentile BMI were found to be higher in women with IR than in women without IR. The median HOMA-IR values were the highest in women with BMI ≥ 25 in both IR (+) and IR (-) groups. No significant difference was found among PCOS phenotypes in terms of HOMA-IR and BMI. Positive correlations were found between BMI, free testosterone and HOMA-IR. However, no correlation was found between AMH and HOMA-IR. The serum AMH levels between women with IR and without IR in PCOS were not significantly different. Also, we did not reveal a correlation between serum AMH levels and IR in women with PCOS. IR was not correlated with different PCOS phenotypes either. We found a positive correlation between BMI and IR. IR should be investigated in women with PCOS having a BMI ≥ 25, independent of their phenotype or AMH levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity

PubMed Central

Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.

2015-01-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

PubMed

Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

2015-08-01

Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

Gestational diabetes mellitus risk factors in women with polycystic ovary syndrome (PCOS).

PubMed

Ashrafi, Mahnaz; Sheikhan, Fatemeh; Arabipoor, Arezoo; Hosseini, Roya; Nourbakhsh, Fereshteh; Zolfaghari, Zahra

2014-10-01

To compare the incidence of gestational diabetes mellitus (GDM) in Iranian infertile women with polycystic ovary syndrome (PCOS) and women without PCOS after pregnancies resulting from either assisted reproductive technology (ART) or spontaneous as well as to determine the risk factors of GDM in PCOS women. In a cross-sectional study, we evaluated medical records of 234 spontaneous pregnant women without PCOS in Akbarabadi Women's Hospital affiliated to Tehran University of Medical Science, Tehran, Iran, along with 234 pregnant women with PCOS and 234 pregnant non-PCOS women with ART conception who were treated at Royan institute, Tehran, Iran, at the same period of time, 2012 to February 2013. Exclusion criteria were as following: maternal age ≥40, family history of diabetes in first-degree relatives, pre-pregnancy diabetes and history of gestational diabetes, history of stillbirth, recurrent miscarriage, birth weight baby ≥4kg (macrosomia), parity >4, Cushing's syndrome, congenital adrenal hyperplasia and overt hypothyroidism. The GDM diagnosis was according to American Diabetes Association (ADA) criteria. Incidence and the risk factors for GDM were evaluated. The incidence rates of GDM were 44.4%, 29.9% and 7.3% for PCOS ART, non-PCOS ART and non-PCOS spontaneous pregnant women, respectively. Multivariable logistic regression was used for determining risk factors of GDM in PCOS women with adjusted odds ratios for age, parity and hypothyroidism, the results revealed the most important and significant predictors for development of GDM in PCOS women as follow: menstrual irregularity (OR=4.2; 95% CI=1.7-10.6), serum triglycerides level ≥150mg/dL (OR=1.9; 95% CI=1.07-3.6) and pregestational metformin use (OR=0.4; 95% CI=0.2-0.7). Pregnant Iranian women with a history of infertility and PCOS are at increased risk for developing GDM. It is recommendable to perform screening test for GDM in PCOS women with ART treatment, irregular menses and high serum

Evaluation of biochemical, endocrine, and metabolic biomarkers for the early diagnosis of polycystic ovary syndrome among non-obese Saudi women.

PubMed

Daghestani, Maha H

2018-05-10

To investigate the potential of selected biochemical, endocrine, and metabolic biomarkers for early diagnosis of polycystic ovary syndrome (PCOS) among non-obese women. A prospective observational cross-sectional study was conducted at three medical centers in Makkah, Saudi Arabia, between July 15 and September 20, 2017. Eligible participants were non-obese women diagnosed with PCOS according to the Rotterdam criteria (n=44) and non-obese normo-ovulatory women without signs of PCOS (control group; n=44). Anthropometric variables related to metabolic profile were determined. Laboratory measures were assessed using fasting blood samples. Waist circumference and waist-to-hip ratio were increased among women with PCOS (both P˂0.001). When compared with the control group, patients in the PCOS group exhibited increases in cholesterol (13.8%), triglycerides (36.6%), low-density lipoprotein (73.2%), fasting glucose (9.2%), fasting insulin (49.4%), luteinizing-hormone/follicle-stimulating-hormone ratio (205.3%), 17β-estradiol (39.2%), testosterone (202.3%), and vascular endothelial growth factor (241.7%) (all P<0.001); and decreases in high-density lipoprotein (-25.3%), progesterone (-7.4%), and sex hormone-binding globulin (-54.0%) (all P<0.001). Vitamin D (P=0.095) and Kisspeptin (P=0.944) levels did not differ between the groups. Various parameters could potentially be used as biomarkers to assess risk of PCOS, even among symptom-free non-obese women. © 2018 International Federation of Gynecology and Obstetrics.

Novel adipokines WISP1 and betatrophin in PCOS: relationship to AMH levels, atherogenic and metabolic profile.

PubMed

Sahin Ersoy, Gulcin; Altun Ensari, Tugba; Vatansever, Dogan; Emirdar, Volkan; Cevik, Ozge

2017-02-01

To determine the levels of WISP1 and betatrophin in normal weight and obese women with polycystic ovary syndrome (PCOS) and to assess their relationship with anti-Müllerian hormone (AMH) levels, atherogenic profile and metabolic parameters Methods: In this prospective cross-sectional study, the study group was composed of 49 normal weighed and 34 obese women with PCOS diagnosed based on the Rotterdam criteria; 36 normal weight and 26 obese age matched non-hyperandrogenemic women with regular menstrual cycle. Serum WISP1, betatrophin, homeostasis model assessment of insulin resistance (HOMA-IR) and AMH levels were evaluated. Univariate and multivariate analyses were performed between betatrophin, WISP1 levels and AMH levels, metabolic and atherogenic parameters. Serum WISP1 and betatrophin values were elevated in the PCOS group than in the control group. Moreover, serum WISP1 and betatrophin levels were higher in the obese PCOS subgroup than in normal weight and obese control subgroups. Multivariate analyses revealed that Body mass index, HOMA-IR, AMH independently and positively predicted WISP1 levels. Serum betatrophin level variability was explained by homocysteine, HOMA-IR and androstenedione levels. WISP1 and betatrophin may play a key role on the pathogenesis of PCOS.

Hypovitaminosis D and Associated Cardiometabolic Risk in Women with PCOS.

PubMed

Mishra, Sanjukta; Das, Ashok Kumar; Das, Swarnalata

2016-05-01

Women with Polycystic Ovary Syndrome (PCOS) frequently suffer from metabolic disturbances like insulin resistance, hypertension and atherogenic dyslipidemia. Accumulating evidences suggest that Vitamin D deficiency is common in PCOS and may be associated with metabolic and endocrinal dysfunctions in PCOS. Thus women with PCOS may be at elevated risk of cardiovascular disease. Present study aims to evaluate Vitamin D status and to assess its association with metabolic and endocrinal dysregulations in women with PCOS, which might help in early identification and prevention of future symptomatic cardiac disease. A total of 44 women with PCOS, diagnosed by Rotterdam criteria and 45 healthy control without PCOS, were evaluated for Vitamin D and cardiometabolic risk factors, including fasting plasma glucose, insulin resistance, dyslipidemia, hs-CRP. That apart, several endocrinal parameters of hyperandrogenism were also examined. Several correlation studies were determined to establish the role of Vitamin D as a cardiometabolic risk factor in PCOS. Results were expressed as mean±SD and were statistically analysed using SPSS software version 16, unpaired student's t-test and Pearson's correlation coefficient. We found lower levels of Vitamin D, which was statistically significant as compared to healthy controls. Hyperinsulinemia, rise in insulin resistance and marked dyslipidemia was observed in the present study. Another relevant finding was significant correlation of Vitamin D with insulin and Homeostatic Model of Assessment- Insulin Resistance Index (HOMA-IR). Hypovitaminosis D was prevalent in PCOS. This was related to metabolic and hormonal disorders in PCOS. Possibly this combined with impaired fasting glucose, IR and dyslipidemia, could account for Cardio vascular risks in PCOS. Further prospective observational studies and randomized control trials are required to explore the above hypothesis.

Lean muscle mass in classic or ovulatory PCOS: association with central obesity and insulin resistance.

PubMed

Mario, F M; do Amarante, F; Toscani, M K; Spritzer, P M

2012-10-01

This age-matched case-control study assessed total and segmental lean muscle mass in classic or ovulatory polycystic ovary syndrome (PCOS) patients and investigated whether lean mass is associated with hormone and metabolic features. Participants underwent anthropometric and clinical evaluation. Habitual physical activity was assessed with a digital pedometer, and body composition by dual-energy X-ray absorptiometry. Laboratory measurements included total cholesterol, cholesterol fractions, triglycerides, glucose, total serum testosterone, serum insulin, estradiol, luteinizing hormone, and SHBG. Energy intake was calculated using a food frequency questionnaire. Classic PCOS patients had higher body mass index (BMI), waist circumference, testosterone and lipid accumulation product values than ovulatory PCOS and controls. Energy consumption, homeostasis model assessment index, SHBG, free androgen index and triglycerides, total and trunk lean mass were higher only in classic PCOS women vs. controls. Arm, leg, trunk, total or limb lean masses were not correlated with hormone levels in any of the groups. However, in PCOS women lipid accumulation product was positively correlated with total (r=0.56, p=0.001), trunk (r=0.59, p=0.001), arm (r=0.54, p=0.001), leg (r=0.44, p=0.03) and limb (r=0.48, p=0.001) lean masses. BMI was positively correlated with all lean mass segments and independently associated with total lean mass. Lipid accumulation product and BMI were independently associated with trunk lean mass variation. The increase in lean mass in classic PCOS appears to be associated with insulin resistance and central obesity rather than with energy intake, physical activity or androgens. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

High Intake of Energy and Fat in Southwest Chinese Women with PCOS: A Population-Based Case-Control Study.

PubMed

Zhang, Jing; Liu, Ying; Liu, Xiaofang; Xu, Liangzhi; Zhou, Lingling; Tang, Liulin; Zhuang, Jing; Guo, Wenqi; Hu, Rong

2015-01-01

Polycystic ovary syndrome (PCOS) is a common reproductive endocrinological disease with heterogeneous phenotype. Obesity contributes to the increased prevalence and severity of PCOS. Whether the intakes of major nutrients are higher in Chinese PCOS patients is still unknown. To study the intakes of total energy, protein, fat and carbohydrate in Southwest Chinese PCOS patients. 1854 women were included in the cross-sectional study. A population-based case-control study was conducted. The dietary habits and nutrients intake status of 169 PCOS patients and 338 age-matched controls were investigated by the method of semi-quantitative food frequency questionnaire. The actual intake of total energy (P = 0.01) and fat (P = 0.01) were higher, but carbohydrate was lower (P = 0.01) in PCOS patients as compared with the controls. The energy percentage supplied by protein (12.33% ± 2.27% vs. 19.26% ± 5.91%, P<0.001) and carbohydrate (48.72% ± 6.41% vs. 68.31% ± 8.37%, P<0.001) were lower in Southwest Chinese PCOS patients than those of control, however, the energy percentage supplied by fat was higher (38.95% ± 5.71% vs. 12.42% ± 5.13%, P<0.001) in PCOS. Limit the intake of total energy and fat shall be recommended to the Southwest Chinese PCOS patients. Women with PCOS in Southwest China shall consult with the nutritionist for improving the dietary structure.

High Intake of Energy and Fat in Southwest Chinese Women with PCOS: A Population-Based Case-Control Study

PubMed Central

Zhang, Jing; Liu, Ying; Liu, Xiaofang; Xu, Liangzhi; Zhou, Lingling; Tang, Liulin; Zhuang, Jing; Guo, Wenqi; Hu, Rong

2015-01-01

Background Polycystic ovary syndrome (PCOS) is a common reproductive endocrinological disease with heterogeneous phenotype. Obesity contributes to the increased prevalence and severity of PCOS. Whether the intakes of major nutrients are higher in Chinese PCOS patients is still unknown. Objectives To study the intakes of total energy, protein, fat and carbohydrate in Southwest Chinese PCOS patients. Methods 1854 women were included in the cross-sectional study. A population-based case-control study was conducted. The dietary habits and nutrients intake status of 169 PCOS patients and 338 age-matched controls were investigated by the method of semi-quantitative food frequency questionnaire. Results The actual intake of total energy (P = 0.01) and fat (P = 0.01) were higher, but carbohydrate was lower (P = 0.01) in PCOS patients as compared with the controls. The energy percentage supplied by protein (12.33%±2.27% vs. 19.26%±5.91%, P<0.001) and carbohydrate (48.72%±6.41% vs. 68.31%±8.37%, P<0.001) were lower in Southwest Chinese PCOS patients than those of control, however, the energy percentage supplied by fat was higher (38.95%±5.71% vs. 12.42%±5.13%, P<0.001) in PCOS. Conclusions Limit the intake of total energy and fat shall be recommended to the Southwest Chinese PCOS patients. Women with PCOS in Southwest China shall consult with the nutritionist for improving the dietary structure. PMID:25993656

Is ovarian reserve associated with body mass index and obesity in reproductive aged women? A meta-analysis.

PubMed

Moslehi, Nazanin; Shab-Bidar, Sakineh; Ramezani Tehrani, Fahimeh; Mirmiran, Parvin; Azizi, Fereidoun

2018-05-07

The associations of body mass index (BMI) and obesity with ovarian reserve are controversial. This systematic review and meta-analysis was conducted to investigate the associations in reproductive-aged women. PubMed and Scopus were searched up to December, 2016. Original studies on the association of BMI with ovarian reserve markers, anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin β, and antral follicle count (AFC), either according to BMI categories or a continuous variable, were selected. Analyses were stratified into three groups based on polycystic ovary syndrome (PCOS) and fertility status of women. Of 4,055 records identified, 45 studies were eligible for inclusion. Comparing the obese with nonobese, the pooled mean differences (MDs) and 95% confidence intervals (CIs) were -1.08 (95% CIs -1.52, -0.63) ng/mL for AMH, -0.22 (95% CIs -0.39, -0.06) mIU/mL for FSH, -0.09 (95% CIs -0.60, 0.42) for AFC, and -21.06 (95% CIs -41.18, -0.85) pg/mL for inhibin β in overall populations. The MDs were significant for AMH in fertile non-PCOS and PCOS women, and for FSH only in PCOS women. Fisher's Z showed significant correlations of BMI with AMH in the overall populations (-0.15 [95% CIs -0.20, -0.11]) and in all subgroups, and with FSH in the fertile non-PCOS women (-0.16 [95% CIs -0.28, -0.04]). Ovarian reserve markers of AMH and FSH are significantly lower in obese than in nonobese women, and BMI is negatively correlated with AMH in all study populations, and with FSH in fertile non-PCOS subgroups. PCOS and fertility status do not appear to affect the associations.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Olszanecka-Glinianowicz, Magdalena; Kuglin, Dorota; Dąbkowska-Huć, Anna; Skałba, Piotr

2011-01-01

It seems that adipokines participate in disturbances of the function of the hypothalamus-pituitary-ovary axis. The aim of the study was to assess the relationship between plasma adiponectin and resistin levels and insulin resistance and markers of hyperandrogenism in lean and obese PCOS women. Forty-one women with PCOS (22 lean and 19 obese) and 16 healthy lean women were enrolled. Body mass and height were measured and body mass index was calculated. In addition to serum glucose, lipids, androgens and insulin, adiponectin and resistin concentration were assessed in the fasting state. The insulin resistance was calculated based on the HOMA-IR. Similar serum resistin concentrations were found in both PCOS subgroups and controls. The obese PCOS subgroup was characterized by the lowest serum adiponectin level (10.8 ± 8.3, compared with 21.0 ± 15.1 in the normal weight PCOS subgroup and 26.7 ± 12.5 μg/ml in controls). There were no correlations between resistin and adiponectin levels and HOMA-IR values and serum androgen concentrations. Significant positive correlations between adiponectin to resistin ratio and plasma FSH (r = 0.49; p = 0.001) and LH (r = 0.45; p = 0.003) concentrations, and a negative correlation with free androgen index (r = -0.34; p = 0.03) in PCOS group were found. Obese but not normal weight PCOS women have lower adiponectin levels whereas resistin concentration did not differ in normal weight and obese PCOS compared to control subjects. We hypothesize that changes of the relative proportion of adiponectin to resistin, but not circulating adiponectin and resistin levels themselves, may play a role in hormonal disturbances but not in insulin resistance in PCOS. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Inositol Treatment and ART Outcomes in Women with PCOS.

PubMed

Garg, Deepika; Tal, Reshef

2016-01-01

Polycystic ovary syndrome (PCOS) affects 5-10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

Developmental origins of polycystic ovary syndrome (PCOS), a case control study comparing birth weight in women with PCOS and control group.

PubMed

Sadrzadeh, Sheda; Painter, Rebecca C; Lambalk, Cornelis B

2016-10-01

Evidence from various epidemiological studies and experimental animal studies has linked adverse intrauterine circumstances with health problems in adult life. This field of investigation is known as Developmental Origins of Health and Disease (DOHaD). Studies investigating the relation between developing polycystic ovary syndrome (PCOS) in adulthood and birth weight have yielded inconsistent results: PCOS is described more often in women with low birth weight and high birth weight, while other studies have failed to establish any relation. In this retrospective case-control study, we evaluated whether women diagnosed with PCOS had lower birth weight compared to women with a regular menstrual cycle (controls). Binary logistic regression models were used to analyze the data and correct for known confounders. About 65 women with PCOS and 96 controls were recruited for this purpose. The average birth weight of PCOS women (3357 g) did not differ from the average birth weight of controls (3409 g). Mean age at menarche differed significantly between groups, 13.7  years and 12.8  years (p = 0.006), respectively, for PCOS women and controls. In conclusion, we could not confirm the effect of adverse intrauterine conditions, reflected in birth weight, on developing PCOS.

Liraglutide increases IVF pregnancy rates in obese PCOS women with poor response to first-line reproductive treatments: a pilot randomized study.

PubMed

Salamun, Vesna; Jensterle, Mojca; Janez, Andrej; Vrtacnik Bokal, Eda

2018-04-27

Glucagon-like peptide-1 (GLP-1) has been investigated in regulation of reproductive system in animal models. The potential impact of short-term preconception intervention with liraglutide on fertility potential in PCOS has not been evaluated yet. A prospective randomized open-label study was conducted in 28 infertile obese PCOS patients (age 31.07±4.75 years, BMI 36.7±3.5 kg/m2, mean±SD). They were assigned to metformin (MET) 1000 mg BID or to MET 1000 mg BID combined with low-dose liraglutide 1.2 mg QD s.c. (COMBI) for 12 weeks. Ovarian stimulation protocol was started after a 4-week medication-free period. The IVF pregnancy rate (PR) was defined as the number of clinical pregnancies confirmed by ultrasound visualization of the fetal cardiac activity, divided by the total number of cycles performed or embryo transfers (ET). The spontaneous PR was followed for 12 months. Patients in the MET group on average lost 7.0±6.0 kg (P=0.001) compared with 7.5±3.9 kg in the COMBI group (P˂0.001) with no significant between-treatment difference (P=0.246). The PR per ET was significantly higher in the COMBI (85.7%) compared with the MET (28.6%) group (P=0.03). The cumulative PR in the time frame of 12 months was 69.2% in the COMBI group compared to 35.7% in the MET group. Preconception intervention with low-dose liraglutide added to metformin is superior to metformin alone in increasing PRs per ET and cumulative PRs in infertile obese women with PCOS, despite comparable weight reduction in both groups. A potential direct crosstalk between GLP-1 and reproductive system needs further exploration.

The role of obesity in the development of polycystic ovary syndrome.

PubMed

Motta, Alicia Beatriz

2012-01-01

Polycystic Ovary Syndrome (PCOS) is one of the common endocrine diseases that affects women in their reproductive age. PCOS has diverse clinical implications that include reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, cardiovascular diseases) and psychological features (increased anxiety, depression and worsened quality of life). The exact patho-physiology of PCOS is complex and remains largely unclear. The prevalence of PCOS is estimated at 4-18%, depending on diverse factors discussed ahead. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and body weight. During the last decades, obesity and excess weight are major chronic diseases all around the word. Obesity increases some features of PCOS such as hyperandrogenism, hirsutism, infertility and pregnancy complications. Both obesity and insulin resistance increase diabetes mellitus type 2 and cardiovascular diseases. Moreover, obesity impairs insulin resistance and exacerbates reproductive and metabolic features of PCOS. It is well known that obesity is associated with anovulation, pregnancy loss and late pregnancy complications (pre-eclampsia, gestational diabetes). Obesity in PCOS is also linked to failure or delayed response to the various treatments including clomiphene citrate, gonadotropins and laparoscopic ovarian diathermy. It has been reported that, after losing as little as 5 % of initial body weight obese women with PCOS improved spontaneous ovulation rates and spontaneous pregnancy. Therefore, the weight loss prior to conception improves live birth rate in obese women with or without PCOS. The treatment of obesity may include lifestyle therapy (diet and exercise), pharmacological treatment and bariatric surgery. In summary, weight loss is considered the first-line therapy in obese women with PCOS. In the present review, the consequence and

Increased Coagulation and Decreased Fibrinolysis as Measured with Overall Hemostatic Potential Are Dependent on BMI and Not Associated with PCOS.

PubMed

Rakusa, Matej; Jensterle, Mojca; Božič-Mijovski, Mojca; Janez, Andrej

2017-05-01

Overall hemostatic potential (OHP) captures all factors that affect coagulation and fibrinolysis cascade. It has not yet been assessed in polycystic ovary syndrome (PCOS). The aim of the study was to identify the relationship of OHP with a syndrome per se and body mass index (BMI). In 90 women with PCOS aged 30.9 ± 8.1 years (50 obese, 13 overweight, and 27 lean) and 21 healthy age-matched controls (11 obese and 10 lean), OHP with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) was determined spectrophotometrically. OFP was calculated. OHP increased with BMI in PCOS (9.6 ± 2.3 in lean, 12.5 ± 5.1 in overweight, and 15.5 ± 3.8 Abs-sum in obese) and in controls (9.1 ± 1.0 in lean and 17.3 ± 4.6 Abs-sum in obese). There was significant difference between lean and obese PCOS (P < 0.001) and between lean and obese controls (P < 0.001). OCP also increased with BMI in PCOS (P < 0.001 for lean vs. obese) and in controls (P < 0.001 for lean vs. obese). OFP decreased with BMI in PCOS (P < 0.001 for obese vs. overweight vs. lean) and in controls (P < 0.001 for obese vs. lean). OHP in healthy obese and obese PCOS did not differ significantly, while OHP for healthy obese was increased in comparison to overweight and lean PCOS (P < 0.001). PCOS was not associated with increased OHP compared with BMI and age-matched controls. However, increase in OHP was positively associated with BMI in PCOS and healthy women.

Is cardiovascular risk in women with PCOS a real risk? Current insights.

PubMed

Papadakis, Georgios; Kandaraki, Eleni; Papalou, Olga; Vryonidou, Andromachi; Diamanti-Kandarakis, Evanthia

2017-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. PCOS incorporates not only symptoms related to the reproductive system but also a clustering of systemic metabolic abnormalities that are linked with increased risk for cardiovascular disease (CVD). More specifically, metabolic aberrations such as impaired glucose and lipid metabolism, accompanied by increased low-grade inflammation as well as elevated coagulation factors appear to contribute to the increased cardiovascular risk. Even though many studies have indicated a rise in surrogate biomarkers of CVD in women with PCOS, it is still doubtful to what extent and magnitude this elevation can be translated to real cardiovascular events. Furthermore, the cardiovascular risk factors appear to vary significantly in the different phenotypes of the syndrome. Women with PCOS have the potential for early atherosclerosis, myocardial and endothelial dysfunction. Whether PCOS women are at real cardiovascular risk compared to controls remains between the verge of theoretical and real threat for the PCOS women at any age but particularly in the post-menopausal state. Interestingly, although the presence of the CVD risk factors is well documented in PCOS women, their combination on different phenotypes may play a role, which eventually results in a spectrum of clinical manifestations of CVD with variable degree of severity. The present manuscript aims to review the interaction between PCOS and the combination of several cardiovascular risk factors.

Prevalence of 'obesity-associated gonadal dysfunction' in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis.

PubMed

Escobar-Morreale, Hector F; Santacruz, Elisa; Luque-Ramírez, Manuel; Botella Carretero, José I

2017-07-01

Sexual dimorphism manifests noticeably in obesity-associated gonadal dysfunction. In women, obesity is associated with androgen excess disorders, mostly the polycystic ovary syndrome (PCOS), whereas androgen deficiency is frequently present in obese men in what has been termed as male obesity-associated secondary hypogonadism (MOSH). Obesity-associated gonadal dysfunction, consisting of PCOS in women and MOSH in men, is a frequent finding in patients with severe obesity and it may be ameliorated or even resolve with marked weight loss, especially after bariatric surgery. We aimed to obtain an estimation of the prevalence of obesity-associated gonadal dysfunction among women and men presenting with severe obesity and to evaluate the response to bariatric surgery in terms of resolution and/or improvement of this condition and changes in circulating sex hormone concentrations. We searched PubMed and EMBASE for articles published up to June 2016. After deleting duplicates, the abstract of 757 articles were analyzed. We subsequently excluded 712 articles leaving 45 studies for full-text assessment of eligibility. Of these, 16 articles were excluded. Hence, 29 studies were included in the quantitative synthesis and in the different meta-analyses. Quality of the studies was assessed using the Quality index for prevalence studies and the Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group available from the National Heart, Lung and Blood Institute. For meta-analyses including more than 10 studies, we used funnel and Doi plots to estimate publication bias. In severely obese patients submitted to bariatric surgery, obesity-associated gonadal dysfunction was very prevalent: PCOS was present in 36% (95CI 22-50) of women and MOSH was present in 64% (95CI 50-77) of men. After bariatric surgery, resolution of PCOS was found in 96% (95CI 89-100) of affected women and resolution of MOSH occurred in 87% (95CI 76-95) of affected men. Sex hormone

Obesity and polycystic ovary syndrome.

PubMed

Naderpoor, N; Shorakae, S; Joham, A; Boyle, J; De Courten, B; Teede, H J

2015-03-01

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited

PubMed Central

Ehrmann, David A.

2016-01-01

Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989–1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired

The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited.

PubMed

Rosenfield, Robert L; Ehrmann, David A

2016-10-01

Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity

Correlation between follicular fluid levels of sRAGE and vitamin D in women with PCOS.

PubMed

Garg, Deepika; Grazi, Richard; Lambert-Messerlian, Geralyn M; Merhi, Zaher

2017-11-01

The pro-inflammatory advanced glycation end products (AGEs) and their anti-inflammatory soluble receptors, sRAGE, play a role in the pathogenesis of PCOS. There is a correlation between vitamin D (vit D) and sRAGE in the serum, whereby vit D replacement increases serum sRAGE levels in women with PCOS, thus incurring a protective anti-inflammatory role. This study aims to compare levels of sRAGE, N-carboxymethyl-lysine (CML; one of the AGEs), and 25-hydroxy-vit D in the follicular fluid (FF) of women with or without PCOS, and to evaluate the correlation between sRAGE and 25-hydroxy-vit D in the FF. Women with (n = 12) or without (n = 13) PCOS who underwent IVF were prospectively enrolled. Women with PCOS had significantly higher anti-Mullerian hormone levels, higher number of total retrieved and mature oocytes, and higher number of day 3 and day 5 embryos formed. Compared to women without PCOS, women with PCOS had significantly lower FF sRAGE levels. In women with PCOS, in women without PCOS, and in all participants together, there was a significant positive correlation between sRAGE and 25-hydroxy-vit D. sRAGE positively correlated with CML in women without PCOS but not in women with PCOS. In women with PCOS, the low ovarian levels of the anti-inflammatory sRAGE suggest that sRAGE could represent a biomarker and a potential therapeutic target for ovarian dysfunction in PCOS. Whether there is a direct causal relationship between sRAGE and vit D in the ovaries remains to be determined.

Phenotypes and enviromental factors: their influence in PCOS.

PubMed

Diamanti-Kandarakis, Evanthia; Christakou, Charikleia; Marinakis, Evangelos

2012-01-01

Polycystic ovary syndrome (PCOS) is a complex syndrome of unclear etiopathogenesis characterized by heterogeneity in phenotypic manifestations. The clinical phenotype of PCOS includes reproductive and hormonal aberrations, namely anovulation and hyperandrogenism, which coexist with metabolic disturbances. Reflecting the crosstalk between the reproductive system and metabolic tissues, obesity not only deteriorates the metabolic profile but also aggravates ovulatory dysfunction and hyperandrogenism. Although the pathogenesis of PCOS remains unclear, the syndrome appears to involve environmental and genetic components. Starting from early life and extending throughout lifecycle, environmental insults may affect susceptible women who finally demonstrate the clinical phenotype of PCOS. Diet emerges as the major environmental determinant of PCOS. Overnutrition leading to obesity is widely recognized to have an aggravating impact, while another detrimental dietary factor may be the high content of food in advanced glycated end products (AGEs). Environmental exposure to industrial products, particularly Bisphenol A (BPA), may also exacerbate the clinical course of PCOS. AGEs and BPA may act as endocrine disruptors in the pathogenesis of the syndrome. PCOS appears to mirror the harmful influence of the modern environment on the reproductive and metabolic balance of inherently predisposed individuals.

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong; Liu, Wei

2017-03-01

Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. Copyright © 2017 by the Endocrine Society

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed Central

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong

2017-01-01

Abstract Context: Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. Objective: This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Design and Setting: Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Main Outcome Measures: Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography–mass spectrometry (MS) and liquid chromatography–MS. Results: Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Conclusions: Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. PMID:27886515

Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).

PubMed

Ojeda-Ojeda, Miriam; Murri, Mora; Insenser, María; Escobar-Morreale, Héctor F

2013-01-01

Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

PubMed

Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

2018-05-01

To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

Serum AMH Level to Predict the Hyper Response in Women with PCOS and Non-PCOS Undergoing Controlled Ovarian Stimulation in ART.

PubMed

Vembu, Radha; Reddy, Nellepalli Sanjeeva

2017-01-01

It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted. To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART. To compare the outcome of stimulation in PCOS and non-PCOS groups. All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam's criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey's post-hoc test was used. Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group ( P = 0.0005). Receiving Operator Curve (ROC) curve was plotted

Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome.

PubMed

Ujvari, D; Hulchiy, M; Calaby, A; Nybacka, Å; Byström, B; Hirschberg, A L

2014-07-01

Does lifestyle intervention aiming at weight loss influence endometrial insulin signaling in overweight/obese women with polycystic ovary syndrome (PCOS)? Lifestyle intervention up-regulates, both at the mRNA and protein levels, components of insulin signaling in the endometrium of overweight/obese PCOS women, in relation to an improved menstrual pattern. PCOS is a multifactorial endocrine disorder diagnosed by two of the following three criteria: chronic anovulation, hyperandrogenism and polycystic ovaries. Many women with PCOS also have insulin resistance and obesity. The syndrome is furthermore associated with endometrial cancer and possible alterations in endometrial function and receptivity. This study assessed the effects of a combined diet and exercise lifestyle intervention for 3 months. A group of 20 overweight/obese PCOS women with anovulation, hyperandrogenism and polycystic ovaries were subjected to a combined diet and exercise program for 3 months. Ten body mass index (BMI)-matched regularly menstruating overweight/obese controls, nine normal-weight PCOS women and ten normal-weight controls were also included in the study. In an academic clinical setting, women were examined in mid-follicular phase for endocrine assessment and determination of endometrial levels of mRNA and immunohistochemical staining of insulin signaling molecules (the insulin receptor, insulin receptor substrate-1 (IRS1) and glucose transporter (GLUT) 1 and 4). Women with PCOS exhibited lower levels of IRS1 (P < 0.01) and GLUT4 (P < 0.01) mRNA in their proliferative endometrium than BMI-matched controls. After lifestyle intervention, weight loss averaged 4.7% and the menstrual pattern improved in 65% of the overweight/obese women with PCOS. Levels of IRS1 (P < 0.01) and GLUT1 (P < 0.05) mRNA were significantly up-regulated in the endometrium of those women with improved menstrual function, as were the protein expression levels of pY612IRS1 (the activated IRS1 form, P < 0.05), pS312

Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society.

PubMed

Wild, Robert A; Carmina, Enrico; Diamanti-Kandarakis, Evanthia; Dokras, Anuja; Escobar-Morreale, Hector F; Futterweit, Walter; Lobo, Rogerio; Norman, Robert J; Talbott, Evelyn; Dumesic, Daniel A

2010-05-01

Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. An expert panel in PCOS and CVD reviewed literature and presented recommendations. Only studies comparing PCOS with control patients were included. All electronic databases were searched; reviews included individual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.

The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs between Women with PCOS and Ovulatory Women.

PubMed

Wei, Daimin; Yu, Yunhai; Sun, Mei; Shi, Yuhua; Sun, Yun; Deng, Xiaohui; Li, Jing; Wang, Ze; Zhao, Shigang; Zhang, Heping; Legro, Richard S; Chen, Zi-Jiang

2018-04-27

Supra-physiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer, compared with physiological estradiol exposure during frozen embryo transfer(FET). Women with polycystic ovary syndrome (PCOS) who usually over-respond to ovarian stimulation have a better live birth rate after elective FET than fresh embryo transfer; however ovulatory women don't. To evaluate whether the discrepancy in live birth rate after fresh versus FET between women with PCOS and ovulatory women was due to the variation in ovarian response, i.e. peak estradiol level or oocyte number. This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS in the first trial and 2157 ovulatory women in the second trial were randomized to undergo either fresh or frozen embryo transfer. The primary outcome was live birth. Compared with fresh embryo transfer, FET resulted in a higher live birth rate(51.9% vs. 40.7%, OR: 1.57, 95%CI: 1.22-2.03) in PCOS women with peak estradiol level >3000pg/ml but not in those with estradiol level ≤3000pg/ml. In PCOS women with oocyte number ≥16, FET yielded a higher live birth rate(54.8% vs. 42.1%, OR: 1.67, 95%CI: 1.20-2.31), but not in those with oocyte number <16. However, in ovulatory women, the pregnancy outcomes were comparable after fresh and FET in all subgroups. Supra-physiological level of estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS; but not in ovulatory women.

PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity.

PubMed

Huang, Zhi Hua; Manickam, Buvana; Ryvkin, Victoria; Zhou, Xiaohong Joe; Fantuzzi, Giamila; Mazzone, Theodore; Sam, Susan

2013-01-01

Adipose tissue macrophage (ATM) infiltration is a major pathway for obesity-induced insulin resistance but has not been studied as a mechanism for insulin resistance in PCOS. We tested whether polycystic ovary syndrome (PCOS) is associated with increased ATM infiltration, especially of inflammatory subtype identified by the CD11c marker. We conducted a case-control study at an academic medical center in the United States. Fourteen PCOS and 14 control women of similar age and body mass index (BMI) underwent a gluteal fat biopsy. Markers of ATM, integrins, TNF-α, and adiponectin, were analyzed by quantitative RT-PCR using a standard curve method. Crown-like structures (CLS) were identified by immunohistochemistry. Abdominal magnetic resonance imaging and frequently sampled i.v. glucose tolerance test were performed to assess abdominal fat and insulin sensitivity (SI). Women with PCOS were compared with control women of similar age and BMI for ATM markers, CLS density, adipose tissue expression of inflammatory cytokines and adiponectin, SI, and abdominal fat depots. Women with PCOS had an increase in CD11c expression (P = 0.03), CLS density (P = 0.001), α5 expression (P = 0.009), borderline increase in TNF-α expression (P = 0.08), and a decrease in adiponectin expression (P = 0.02) in gluteal adipose tissue. Visceral (P = 0.009) and sc abdominal fat (P = 0.005) were increased in PCOS. SI was lower in PCOS (P = 0.008). PCOS is associated with an increase in CD11c expression and CLS density and a decrease in adiponectin expression in sc adipose tissue. Additionally, PCOS is associated with higher central abdominal fat depots independent of BMI. These alterations are present among mostly nonobese women and could represent mechanisms for insulin resistance.

Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.

PubMed

Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

2013-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.

Differential Contributions of Polycystic Ovary Syndrome (PCOS) Manifestations to Psychological Symptoms.

PubMed

McCook, Judy G; Bailey, Beth A; Williams, Stacey L; Anand, Sheeba; Reame, Nancy E

2015-07-01

The purpose of this study was to investigate the relative contributions of previously identified Polycystic ovary syndrome (PCOS) manifestations (infertility, hirsutism, obesity, menstrual problems) to multiple psychological symptoms. Participants were 126 female endocrinology patient volunteers diagnosed with PCOS who completed a cross-sectional study of PCOS manifestations and psychological symptoms. Participants had significantly elevated scores on nine subscales of psychological symptoms. Menstrual problems were significantly associated with all symptom subscales as well as the global indicator, while hirsutism and obesity were significantly related to five or more subscales. After controlling for demographic factors, menstrual problems were the strongest predictor of psychological symptoms. Findings suggest features of excess body hair, obesity, and menstrual abnormalities carry unique risks for adverse psychologic symptoms, but menstrual problems may be the most salient of these features and deserve particular attention as a marker for psychological risk among women with PCOS.

Serum levels of TSP-1, NF-κB and TGF-β1 in polycystic ovarian syndrome (PCOS) patients in northern China suggest PCOS is associated with chronic inflammation.

PubMed

Liu, Meimei; Gao, Jiayin; Zhang, Yanhua; Li, Peiling; Wang, Hongli; Ren, Xiaopang; Li, Changmin

2015-12-01

The objective of this study was to determine the levels of thrombospondin-1 (TSP-1), transforming growth factor-β1 (TGF-β1) and nuclear factor kappaβ (NF-κβ) in polycystic ovarian syndrome (PCOS) patients with and without insulin resistance and after treatment with cyproterone acetate/ethinyloestradiol with or without concomitant metformin. Prospective. Patients with PCOS and healthy women were recruited. Patients were subdivided into obese and nonobese based on body mass index. Patients with PCOS were also grouped according to homoeostasis model assessment-insulin resistance (HOMA-IR) ≥ 2·69 or <2·69, and by PCOS phenotype. Patients with PCOS-IR were treated with a 6-month course of cyproterone acetate/ethinyloestradiol with or without concomitant metformin. Inflammatory markers were examined at baseline, and after 6 months of treatment. A total of 445 women with PCOS (mean age 25·9 ± 2·7 years; 298 obese, 147 nonobese) and 213 normal controls (mean age 24·9 ± 3·0 years) were included. Regardless of obesity status, testosterone, free androgen index (FAI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, HOMA-IR, TSP-1 and NF-κB in the PCOS groups were significantly higher than in the control group, whereas TSP-1 was lower in the PCOS groups (all, P < 0·05). Patients with PCOS without IR had lower TSP-1 levels than control patients (P < 0·05). Treatment with cyproterone acetate/ethinyloestradiol with addition of metformin reduced the level of NF-κB, TGF-β1 and HOMA-IR and increased the level of TSP-1. These results support the association between PCOS and chronic inflammation. © 2015 John Wiley & Sons Ltd.

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder.

PubMed

Torchen, Laura C

2017-11-11

Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed.

The impact of hyperandrogenism in female obesity and cardiometabolic diseases associated with polycystic ovary syndrome.

PubMed

Barber, Thomas M; Vojtechova, Petra; Franks, Stephen

2013-09-01

Polycystic ovary syndrome (PCOS) is a common condition characterized by reproductive and hyperandrogenic features and is often associated with obesity and metabolic dysfunction. Overall, women with PCOS have a substantially greater prevalence of metabolic syndrome than women from the general population. Furthermore, PCOS per se (independent of its frequent association with obesity) often confers cardiometabolic risk (including insulin resistance), and its concurrence with obesity often represents a metabolic "double-whammy" from the adverse effects of PCOS and obesity. The introduction of the Rotterdam diagnostic criteria for PCOS in 2003 has broadened the scope of this condition. The Rotterdam diagnostic criteria have also introduced two new phenotypic subgroups (including normoandrogenemic women with PCOS) that have provided novel insights into a potential role for hyperandrogenism in the development of adverse cardiometabolic risk in women with PCOS. Based on evidence from cross-sectional and interventional studies, hyperandrogenism, obesity, and cardiometabolic risk in women appear to be linked through complex and multidirectional pathways. Furthermore, data from obese women without a formal diagnosis of PCOS also suggest that these interrelationships often exist in female obesity per se (in milder forms than occurs in PCOS). Data from female-to-male transsexuals are particularly informative because these show direct effects of hyperandrogenism (induced through exogenous use of androgenic therapies) on fat distribution and cardiometabolic risk in women. A challenge for the future will be to disentangle and improve our understanding of this complex pathogenic web, thereby facilitating novel and targeted therapies for the hyperandrogenic and adverse cardiometabolic manifestations of PCOS.

Weight Management Interventions in Women with and without PCOS: A Systematic Review.

PubMed

Kataoka, Josefin; Tassone, Eliza C; Misso, Marie; Joham, Anju E; Stener-Victorin, Elisabet; Teede, Helena; Moran, Lisa J

2017-09-08

Polycystic ovary syndrome (PCOS) is a common endocrinopathy among women associated with reproductive, metabolic and psychological features. While weight management is recommended as first-line treatment, it is unclear if women with PCOS achieve similar benefits as women without PCOS. This systematic review thus aimed to compare the efficacy of weight management interventions in women with and without PCOS. Databases were searched until May 2017. The primary outcome was weight and anthropometric, reproductive, metabolic and psychological measures were secondary outcomes. Of 3264 articles identified, 14 studies involving n = 933 ( n = 9 high and n = 5 moderate risk of bias) met the inclusion criteria. No statistically significant differences in weight or weight loss following the intervention were found between women with and without PCOS in five studies, with the remaining studies not comparing the difference in weight or weight loss between these groups. Secondary outcomes did not differ significantly between the two groups. This review identified that there is a paucity of high quality research in this area and that more rigorous research is needed.

Weight Management Interventions in Women with and without PCOS: A Systematic Review

PubMed Central

Kataoka, Josefin; Tassone, Eliza C.; Misso, Marie; Joham, Anju E.; Moran, Lisa J.

2017-01-01

Polycystic ovary syndrome (PCOS) is a common endocrinopathy among women associated with reproductive, metabolic and psychological features. While weight management is recommended as first-line treatment, it is unclear if women with PCOS achieve similar benefits as women without PCOS. This systematic review thus aimed to compare the efficacy of weight management interventions in women with and without PCOS. Databases were searched until May 2017. The primary outcome was weight and anthropometric, reproductive, metabolic and psychological measures were secondary outcomes. Of 3264 articles identified, 14 studies involving n = 933 (n = 9 high and n = 5 moderate risk of bias) met the inclusion criteria. No statistically significant differences in weight or weight loss following the intervention were found between women with and without PCOS in five studies, with the remaining studies not comparing the difference in weight or weight loss between these groups. Secondary outcomes did not differ significantly between the two groups. This review identified that there is a paucity of high quality research in this area and that more rigorous research is needed. PMID:28885578

Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls.

PubMed

Schmidt, Johanna; Brännström, Mats; Landin-Wilhelmsen, Kerstin; Dahlgren, Eva

2011-07-01

The hormonal and anthropometric profile of premenopausal women with polycystic ovary syndrome (PCOS) is well described, but there is a lack of data concerning changes in these variables into the postmenopausal period. Our objective was to examine whether PCOS women differ from normal women regarding levels of reproductive hormones, anthropometry, and presence of hirsutism/climacteric symptoms also after menopause. In this prospective study, women with PCOS (61-79 yr) and age-matched controls, examined in 1987, were reinvestigated at a university hospital. Twenty-five PCOS patients (Rotterdam criteria) and 68 controls (randomly allocated from the Gothenburg WHO MONICA study) participated. Reexamination and hormonal measurements were done 21 yr after previous visit. FSH, LH, TSH, thyroid peroxidase antibodies, prolactin, estrone, estradiol, SHBG, androstenedione, total testosterone, dehydroepiandrosterone sulfate, free androgen index, and anthropometry were determined. Presence of climacteric symptoms, hirsutism, and menopausal age were recorded. PCOS women had higher free androgen index (P = 0.001) but lower FSH (P < 0.001) and SHBG (P < 0.01) than controls. Menopausal age, body weight, body mass index, waist to hip ratio, LH, prolactin, androstenedione, dehydroepiandrosterone sulfate, total testosterone, estradiol, and estrone were similar in PCOS and controls. Women with PCOS reported hirsutism more frequently (P < 0.001) but had fewer climacteric symptoms (P < 0.05) and hypothyroidism than controls (P < 0.05). PCOS women differ from controls with regard to levels of certain reproductive hormones also after menopause, but the established premenopausal increase in waist to hip ratio in PCOS patients disappeared after menopause, mainly due to weight gain among controls. A novel finding was the lower prevalence of hypothyroidism in PCOS women.

No phenotypic differences for polycystic ovary syndrome (PCOS) between women with and without type 1 diabetes mellitus.

PubMed

Amato, M C; Guarnotta, V; Ciresi, A; Modica, R; Pantò, F; Giordano, C

2014-01-01

Women with type 1 diabetes mellitus (DM1) have a higher prevalence of polycystic ovary syndrome (PCOS) than the general population. The aim of this study was to clarify, in DM1 women with PCOS (PCOS-DM1), the influence of insulin therapy and glycemic control and evaluate the hormonal and phenotypic differences with age-matched and body mass index (BMI)-matched women with PCOS without diabetes. We evaluated 103 DM1 women with and without PCOS treated with intensive insulin therapy; 38 age-matched and BMI-matched women with PCOS without diabetes were compared in a cross-sectional study. Clinical, anthropometric, and metabolic parameters were evaluated. Hormonal evaluation and ovary ultrasound were performed during the follicular phase of the menstrual cycle. Applying the diagnostic criteria of the Androgen Excess Society, 38 (36.89%) women with DM1 showed PCOS. The 38 PCOS-DM1 women showed no differences in treatment and glycemic control compared with DM1 women without PCOS. The only difference was a higher visceral adiposity index in PCOS-DM1 (1.21±0.70 vs 0.90±0.32; P=.002). PCOS-DM1 showed no phenotypic differences with age-matched and BMI-matched PCOS without diabetes. The hormonal pattern was similar except that higher levels of Δ4androstenedione were found in PCOS-DM1 (12.89±3.49 vs 2.79±1.75 nmol/L; P=.010). The women with PCOS-DM1 do not exhibit particular phenotypic characteristics compared with nondiabetic women with PCOS. However, this pathological disorder must not be underestimated because it could be an additional cardiovascular risk factor in women with DM1.

Cardiotrophin-1 as a new metabolic biomarker in women with PCOS.

PubMed

Anik Ilhan, Gokce; Kanlioglu, Cansu; Arslan, Gaye; Yildizhan, Begum; Pekin, Tanju

2018-03-30

The objective of this study was to investigate cardiotrophin-1 (CT-1) levels as a new metabolic biomarker in women with polycystic ovary syndrome (PCOS). One hundred consecutive women with PCOS were divided into two groups according to presence of metabolic syndrome as MetS+ and MetS-. Clinical, hormonal and metabolic parameters in addition to CT-1 levels were compared between the groups. Correlation analyses were performed between CT-1 and clinical and metabolic parameters in women with PCOS. One hundred PCOS subjects were enrolled in the study, of which 29 subjects were diagnosed with metabolic syndrome. WHR, systolic and diastolic blood pressures, triglyceride, total cholesterol, HOMA-IR, FAI, FGS and CT-1 levels were significantly higher in the MetS+ group compared with the MetS- group. HDL cholesterol was significantly higher in the MetS- group than the MetS+ one. CT-1 levels were found to be positively correlated with diastolic blood pressure, TG levels and FGS. Cardiotrophin-1 may be a promising new metabolic biomarker in women with PCOS. CT-1 may be beneficial for estimating the risk of long-term adverse health consequences and establishing early intervention and preventation strategies.

Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS.

PubMed

Dokras, Anuja; Sarwer, David B; Allison, Kelly C; Milman, Lauren; Kris-Etherton, Penny M; Kunselman, Allen R; Stetter, Christy M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Fleming, Jennifer; Coutifaris, Christos; Legro, Richard S

2016-08-01

Polycystic ovary syndrome (PCOS) is associated with reduced health-related quality of life (HRQOL) and increased prevalence of depressive and anxiety disorders. The impact of PCOS-specific treatments on these co-morbidities is unclear. To assess the impact of weight loss and decreasing hyperandrogenism on HRQOL and mood and anxiety disorders in women with PCOS. A secondary analysis of a randomized controlled trial (OWL-PCOS) of preconception treatment conducted at two academic centers in women (age, 18-40 years; body mass index, 27-42 kg/m(2)) with PCOS defined by Rotterdam criteria. Continuous oral contraceptive pill (OCP) or intensive lifestyle intervention or the combination (Combined) for 16 weeks. Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ. The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ. All three interventions resulted in significant improvement in the general health score on the SF-36. Both the OCP and Combined groups showed improvements in all domains of the PCOSQ (P < .01) compared to baseline scores. The Combined group had significant improvements in the weight, body hair, and infertility domains compared to a single treatment group (P < .05). In a linear regression model, change in weight correlated with improvements in the weight domain (P < .001) and physical well-being (P < .02), change in T correlated with improvements in the hair domain (P < .001), and change in both weight and T correlated with the infertility (P < .001) and menstrual domains (P < .05). Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life, depressive symptoms, and anxiety disorders, and combined therapies offer further benefits in overweight/obese women with PCOS.

PON1 promoter polymorphisms contribute to PCOS susceptibility and phenotypic outcomes in Indian women.

PubMed

Dadachanji, Roshan; Shaikh, Nuzhat; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

2018-06-30

Polycystic ovary syndrome is a common endocrinopathy characterized by anovulatory infertility, hyperandrogenism, insulin resistance and oxidative stress, which predisposes affected women to reproductive and cardiometabolic complications in later life. We have investigated the association of PON1 promoter polymorphisms with PCOS susceptibility, PON1 activity and its related traits in Indian women. The genotypic and allelic frequency distribution of only -907G/C polymorphism in PON1 promoter showed significant difference between non-hyperandrogenic control and PCOS women, and was significantly associated with reduced susceptibility to PCOS, considering the recessive model. PON1 lactonase and arylesterase activities were also significantly decreased in women with PCOS compared to controls. Further, PON1 promoter polymorphisms were linked to altered insulin and testosterone levels in hyperandrogenic and non-hyperandrogenic women with PCOS. This study highlights PON1 as an important candidate gene influencing genetic pathophysiology of PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinically significant and sustained weight loss is achievable in obese women with polycystic ovary syndrome followed in a regular medical practice.

PubMed

Pelletier, Lysanne; Baillargeon, Jean-Patrice

2010-12-01

To determine the proportion of obese women with polycystic ovary syndrome (PCOS) losing clinically significant amounts of weight during a standard follow-up by an endocrinologist. Retrospective cohort study. Reproductive Endocrinology Clinic of an academic center. Obese patients with PCOS assessed between May 2002 and September 2008. General nonstandardized advice on weight loss and exercise. Proportion of women losing ≥5% or ≥10% of their initial weight at each of the following time interval: 2-6 months, 6-12 months, 12-18 months, 18-24 months, 24-36 months, and beyond 36 months. One hundred seventeen patients with PCOS and with a mean body mass index (BMI) of 38.7 kg/m(2) and mean age of 28.5 years were followed-up for a median duration of 21.9 months (range, 2.0-61.8 months), with a median of two visits per year. More than 40% of these women lost ≥5% of their initial weight after >6 months of follow-up, and ≥20% lost ≥10% after 1 year of follow-up. More important, these proportions were maintained up to ≥3 years. It is possible for obese women with PCOS to achieve clinically significant and sustained weight loss by following simple advices given in a regular clinical care setting. Therefore, practitioners should not underestimate their impact to facilitate weight loss in women with PCOS. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

PubMed Central

Torchen, Laura C.

2018-01-01

Purpose of Review Polycystic ovary syndrome (PCOS) is diagnosed by its characteristic reproductive features. However, PCOS is also associated with metabolic abnormalities, including insulin resistance and β-cell dysfunction. The severity of these abnormalities varies according to the reproductive phenotype, with the so-called NIH or classic phenotype conferring the greatest metabolic risk. The increased risk for type 2 diabetes (T2D) is well-established among affected women with the NIH phenotype, but whether PCOS also confers an increased risk for cardiovascular events remains unknown. Recent Findings Recent studies in daughters of affected women have found evidence for pancreatic β-cell dysfunction prior to menarche. Further, genetic analyses have provided evidence that metabolic abnormalities such as obesity and insulin resistance contribute to the pathogenesis of PCOS. Summary PCOS increases the risk for T2D. However, the risk for cardiovascular disease has not been quantified, and prospective, longitudinal studies are still critically needed. PMID:29128916

Higher levels of circulating chemerin in both lean and obese patients with polycystic ovary syndrome.

PubMed

Ademoglu, E; Berberoglu, Z; Carlioglu, A; Dellal, F; Gorar, S; Alphan, Z; Uysal, S; Karakurt, F

2014-12-01

The aim of this paper was to compare serum chemerin levels in nonobese and overweight/obese patients with polycystic ovary syndrome (PCOS) with lean controls. Seventy women with newly diagnosed or untreated PCOS and 38 age-matched nonobese healthy controls were enrolled in the present study. Participants with PCOS were categorized as nonobese (Body Mass Index [BMI] <25 kg/m², N.=36) or overweight/obese (BMI 25-29.9 kg/m² and ≥30 kg/m², respectively, N.=34). Anthropometric, metabolic and hormonal patterns, and serum chemerin were measured. Serum chemerin tended to be higher in obese PCOS group than in nonobese PCOS women but did not reach statistical significance. Nonobese healthy controls had significantly lower chemerin levels than two PCOS groups (P<0.001). Fasting insulin (P<0.05) and homeostasis model assessment index (P<0.05) were significantly higher in obese women with PCOS than in other two groups. Also, these two parameters were higher in lean patients with PCOS than in healthy controls (P<0.05). In multiple linear regression analyses, chemerin was significantly associated with BMI (β-coefficient =0.336, P<0.01), and triglyceride (β-coefficient =0.298, P<0.05). Chemerin levels were significantly increased not only in obese PCOS women but also in nonobese PCOS women. The physiological significance of elevated serum chemerin in PCOS remains unclear.

GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome.

PubMed

Dantas, Wagner Silva; Marcondes, José Antonio Miguel; Shinjo, Samuel Katsuyuki; Perandini, Luiz Augusto; Zambelli, Vanessa Olzon; Neves, Willian Das; Barcellos, Cristiano Roberto Grimaldi; Rocha, Michele Patrocínio; Yance, Viviane Dos Reis Vieira; Pereira, Renato Tavares Dos Santos; Murai, Igor Hisashi; Pinto, Ana Lucia De Sá; Roschel, Hamilton; Gualano, Bruno

2015-11-01

The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL). Fifteen women with obesity and PCOS and 12 body mass index-matched CTRL participated in this study. Subjects performed a 40-min single bout of exercise. Muscle biopsies were performed before and 60 min after exercise. Selected proteins were assessed by Western blotting. CTRL, but not PCOS, showed a significant increase in PI3-k p85 and AS160 Thr 642 after a single bout of exercise (P = 0.018 and P = 0.018, respectively). Only PCOS showed an increase in Akt Thr 308 and AMPK phosphorylation after exercise (P = 0.018 and P = 0.018, respectively). Total GLUT4 expression was comparable between groups (P > 0.05). GLUT4 translocation tended to be significantly higher in both groups after exercise (PCOS: P = 0.093; CTRL: P = 0.091), with no significant difference between them (P > 0.05). A single bout of exercise elicited similar GLUT4 translocation in skeletal muscle of PCOS and CTRL, despite a slightly differential pattern of protein phosphorylation. The absence of impairment in GLUT4 translocation suggests that PCOS patients with obesity and insulin resistance may benefit from exercise training. © 2015 The Obesity Society.

In women with polycystic ovary syndrome and obesity, loss of intra-abdominal fat is associated with resumption of ovulation.

PubMed

Kuchenbecker, Walter K H; Groen, Henk; van Asselt, Sophie J; Bolster, Johanna H T; Zwerver, J; Slart, Riemer H J; Vd Jagt, Erik J; Muller Kobold, Anneke C; Wolffenbuttel, Bruce H R; Land, Jolande A; Hoek, Annemieke

2011-09-01

It is not clear why some anovulatory women with polycystic ovary syndrome (PCOS) and obesity resume ovulation and others remain anovulatory after weight loss. The objective of this study was to compare the changes in body fat distribution and specifically intra-abdominal fat (IAF) and subcutaneous abdominal fat (SAF) between a group of anovulatory women with PCOS and obesity who resume ovulation (RO+) to those who remain anovulatory (RO-) during a lifestyle program. In a prospective pilot cohort study, anovulatory women with PCOS underwent a 6 month lifestyle program in a tertiary fertility clinic. Body fat distribution was assessed by anthropometrics, dual-energy X-ray absorptiometry (DEXA) and single slice abdominal CT scan at intake, after 3 months and after 6 months. Baseline-corrected changes over time were analysed using generalized estimating equations longitudinal regression analysis. In 32 anovulatory women with PCOS (age, 28 ± 4 years; BMI, 37.5 ± 5.0 kg/m²), there were no significant baseline differences in anthropometrics and biochemical assessment between 14 RO+ participants and 18 RO- participants. RO+ women lost more weight (6.3 versus 3.0%) and abdominal fat on DEXA (15.0 versus 4.3%) compared with RO- women. Resumption of ovulation was associated with early and consistent loss of IAF (12.4 versus 5.0% at 3 months and 18.5 versus 8.6% at 6 months). Loss of SAF between the RO+ women and the RO- women was similar at 3 months (6.2 versus 6.1%) but did not change any further in RO- women (6.1%) as it did in RO+ women (11.4%) at 6 months. In anovulatory women with PCOS and obesity undergoing a lifestyle program, RO+ women lose more body weight and abdominal fat on DEXA than RO- women. In addition, this study shows that early and consistent loss of IAF is associated with resumption of ovulation. Future studies should address the mechanisms behind these changes and should assess interventions aimed at loss of IAF to facilitate resumption of ovulation.

The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls.

PubMed

Kahal, Hassan; Aburima, Ahmed; Ungvari, Tamas; Rigby, Alan S; Coady, Anne M; Vince, Rebecca V; Ajjan, Ramzi A; Kilpatrick, Eric S; Naseem, Khalid M; Atkin, Stephen L

2015-04-02

Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight. Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month - baseline) ± standard deviation. Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls -0.17 ± 0.26 but not PCOS -0.12 ± 0.28; between groups difference, 95% confidence interval = -0.14 - 0.26, P = 0.41. No significant changes were noted in cIMT or RHI. Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3-4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity

Cardiovascular Risk Factors in Bulgarian Patients with Polycystic Ovary Syndrome and/or Obesity

PubMed Central

Gateva, Antoaneta; Kamenov, Zdravko

2012-01-01

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disturbances in women of reproductive age. Besides its well-known effects on reproductive health, it is also linked to increased cardiovascular risk in later life. The aim of this study is to investigate some classical cardiovascular risk factors in a crossectional study of Bulgarian women with PCOS and/or obesity. We performed a retrospective medical chart review of 375 women from an university endocrine clinic. We found significant differences in the indices of carbohydrate metabolism, blood pressure, lipid profile, rate of liver steatosis, and the levels liver enzymes and hematological results between the lean and obese PCOS women. Obese women without PCOS did not show significantly different results in their OGGT form obese PCOS women. Waist-to-stature-ratio (WSR) correlated better with the baseline IRI levels and lipid profile than waist-to-hip-ratio (WHR) that makes it a better marker for unfavorable metabolic profile. PMID:22262974

Daytime decrease of prolactin levels is associated with PCOS regardless to nutritional status and other hormones levels.

PubMed

Franik, Grzegorz; Madej, Paweł; Guz-Lem, Magdalena; Owczarek, Aleksander; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena

2017-05-01

The aim of the study is to analyze daytime changes of prolactin level depending on nutritional status and polycystic ovary syndrome (PCOS). One hundred and fifteen (69 normal weight, 21 overweight and 25 obese) diagnosed with PCOS and 77 (37 normal weight, 18 overweight and 22 obese) women - Non-PCOS without concomitant diseases were enrolled. Body mass and height were measured and BMI was calculated. Serum concentrations of FSH, LH, E2, testosterone, TSH and PRL were determined morning 6.00 a.m. after wake. Second measurement of PRL was performed at 4 p.m. The daytime decrease of prolactin level was higher in PCOS than in Non-PCOS group regardless of nutritional status (normal weight 35.8 ± 26.0 vs. 24.3 ± 15.3 ng/mL; overweight 28.5 ± 25.4 vs. 17.5 ± 8.8 ng/mL and obese 23.2 ± 21.1 vs. 18.4 ± 11.6 ng/ml, respectively). However, in both PCOS and Non-PCOS daytime changes of prolactin level were higher in normal weight than overweight and obese women (35.8 ± 26.0 vs. 28.5 ± 25.4 vs. 23.2 ± 21.1 ng/mL and 24.3 ± 15.3 vs. 17.5 ± 8.8 vs. 18.4 ± 11.6 ng/mL, respectively). The multivariate regression analysis revealed that the daytime changes of prolactin level are proportional to TSH concentration and coexistence of PCOS as well as inversely relative to BMI. In conclusions, our results suggest that overweight and obesity decreased morning PRL level and impaired its daytime decrease, but coexistence of PCOS enlarged its.

In vitro fertilization outcomes in obese women under and above 35 years of age.

PubMed

Vural, F; Vural, B; Çakiroglu, Y

2016-01-01

To explore the impact of obesity on in vitro fertilization (IVF) outcomes and comparing the results with regards to age groups. This retrospective cohort recruited 780 women that underwent IVF. Women with polycystic ovarian syndrome (PCOS) were excluded from the study. Women under and above 35 years were categorized into three groups as normal weight, overweight, and obese. The main outcome measures were ovarian response, oocyte maturity, and clinical pregnancy rates. Despite oocyte count and fertilization rate that decreased in both younger and older obese women, this difference was not statistically significant. After age matched-normal weight controls, the clinical pregnancy rates were significantly decreased in older obese women. On the other hand, poor ovarian response observed significantly in young obese women without effect on pregnancy rates. These results suggested that obesity in young and old women has different outcomes and different steps of IVF process may be affected.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.

PubMed

Kollmann, M; Klaritsch, P; Martins, W P; Guenther, F; Schneider, V; Herzog, S A; Craciunas, L; Lang, U; Obermayer-Pietsch, B; Lerchbaum, E; Raine-Fenning, N

2015-10-01

Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. Retrospective matched cohort study. Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be

Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients.

PubMed

Genazzani, Alessandro D; Santagni, Susanna; Rattighieri, Erika; Chierchia, Elisa; Despini, Giulia; Marini, Giulia; Prati, Alessia; Simoncini, Tommaso

2014-06-01

Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects fertility through oligo-ovulation, hyperandrogenism and polycystic morphology of the ovaries. Since it has been demonstrated a high incidence of insulin resistance in PCOS patients, our study aimed to evaluate the efficacy of the integrative treatment with D-chiro-inositol (DCI) (500 mg die, per os, for 12 weeks) on hormonal parameters and insulin sensitivity in a group of overweight/obese PCOS patients (body mass index; BMI > 26). After the treatment, interval several endocrine parameters improved (luteinizing hormone [LH], LH/follicle stimulating hormone [FSH], androstenedione and insulin), insulin response to oral glucose tolerance test reported the significant improvement of insulin sensitivity as well as the gonadotropin-releasing hormone (GnRH)-induced (10 µg, in bolus) LH response. BMI decreased, though no lifestyle modification was requested. When data were analyzed according to the presence or absence of first-grade diabetic relatives, PCOS patients with diabetic relatives showed greater improvement after DCI administration. In conclusion DCI administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives.

A case of idiopathic intracranial hypertension associated with PCOS.

PubMed

Lee, Y J; Jeong, J E; Joo, J K; Lee, K S

2015-01-01

Idiopathic intracranial hypertension (IIH) is a rare neurologic disorder. It is also known as pseudotumor cerebri. The incidence of IIH is one to two per 100,000 population annually. The higher incidence is in obese women from 15 to 44 years. The main symptoms are headache and visual loss. It mostly affects women of childbearing age who are overweight or obese. There are many theories of pathogenesis of IIH, but precise pathogenesis is unknown. One of the causes of IIH is intracranial venous sinus thrombosis. It can cause increased cerebrospinal fluid (CSF) pressure by obstruction of venous outflow and blocking of CSF absorption. In polycystic ovary syndrome (PCOS) patients, thrombogenic tendency is increased due to increased aromatization of testosterone to estradiol which could induce estrogen-mediated thrombophilia. The authors present a 14-year-old girl with PCOS stigma who presented with a severe headache and papilledema. These symptoms were not improved by standard medical therapy of IIH and PCOS, but improved after laparoscopic ovarian drilling. The authors report it with a review of the literature.

Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference?

PubMed

Liepa, George U; Sengupta, Aditi; Karsies, Danielle

2008-02-01

Polycystic ovary syndrome (PCOS) is a condition that involves the excess production of androgens. It affects up to 10% of all American women and can lead to the development of acne, hirsutism, and infertility. It has also been associated with coronary heart disease, diabetes, and metabolic syndrome. Over half of the women who are diagnosed with PCOS are overweight or obese. Recommendations are made for overweight/obese women to lose weight via diet and exercise. Women with PCOS should also consider maintaining a diet that is patterned after the type 2 diabetes diet. This diet includes an increase in fiber and a decrease in refined carbohydrates, as well as a decrease in trans and saturated fats and an increase in omega-3 and omega-9 fatty acids. Foods that contain anti-inflammatory compounds (fiber, omega-3 fatty acids, vitamin E, and red wine) should also be emphasized. Evidence is provided for the impact of these dietary changes on improvements in the androgen profile of PCOS patients.

The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials.

PubMed

Hoeger, Kathleen; Davidson, Kristen; Kochman, Lynda; Cherry, Tracy; Kopin, Laurie; Guzick, David S

2008-11-01

Polycystic ovary syndrome (PCOS) presents in adolescence, and obesity is a common finding. The benefits and risks of alternate approaches to the management of PCOS in obese adolescent women are not clear. We investigated the effects of metformin, oral contraceptives (OCs), and/or lifestyle modification in obese adolescent women with PCOS. Two small, randomized, placebo-controlled clinical trials were performed. A total of 79 obese adolescent women with PCOS participated. In the single treatment trial, subjects were randomized to metformin, placebo, a lifestyle modification program, or OC. In the combined treatment trial, all subjects received lifestyle modification and OC and were randomized to metformin or placebo. Serum concentrations of androgens and lipids were measured. Lifestyle modification alone resulted in a 59% reduction in free androgen index with a 122% increase in SHBG. OC resulted in a significant decrease in total testosterone (44%) and free androgen index (86%) but also resulted in an increase in C-reactive protein (39.7%) and cholesterol (14%). The combination of lifestyle modification, OC, and metformin resulted in a 55% decrease in total testosterone, as compared to 33% with combined treatment and placebo, a 4% reduction in waist circumference, and a significant increase in HDL (46%). In these preliminary trials, both lifestyle modification and OCs significantly reduce androgens and increase SHBG in obese adolescents with PCOS. Metformin, in combination with lifestyle modification and OC, reduces central adiposity, reduces total testosterone, and increases HDL, but does not enhance overall weight reduction.

Reactive hypoglycemia in lean young women with PCOS and correlations with insulin sensitivity and with beta cell function.

PubMed

Altuntas, Yuksel; Bilir, Muammer; Ucak, Sema; Gundogdu, Sadi

2005-04-01

Reactive hypoglycemia (RH), which is a postprandial hypoglycemic state, occurs within 2-5 h after food intake. It is classified as idiopathic, alimentary, or diabetic reactive hypoglycemia. We studied the incidence of reactive hypoglycemia and looked for any correlations between it and the presence of insulin sensitivity and/or beta cell function in young lean polycystic ovary syndrome (PCOS) patients. This study was designed as a cross-sectional study in 64 lean young women with PCOS (BMI < or = 25 kg/m2). Various indices of insulin sensitivity and beta cell function derived from the oral glucose tolerance test (OGTT) results were used. We found the rate of RH to be 50% in lean young women with PCOS. DHEA-S and PRL levels were found to be lower in subjects with RH (P < 0.05 and P > 0.05, respectively). Beta cell function indices such as the insulinogenic index (at 120 min), CIR (at 120 min) and HOMA beta cell index were found to be insignificantly higher in the RH group than the nonreactive hypoglycemia (NRH) group. The 4 h glucose level, but not the 3 h glucose level, was significantly correlated with insulin resistance indices, such as fasting insulin level, HOMA-IR, Quicky index, and FIRI in the RH group. Significantly decreased DHEA-S levels were an interesting finding. In conclusion, there is an urgent need to investigate RH in lean young women with PCOS. Our results indicate that more definite insulin resistance occurs in subjects with RH in the fourth hour of the OGTT than those with RH in the third hour. In addition, RH in the fourth hour together with a low DHEA-S level may be predictive of future diabetes in young women with PCOS even when they are not obese.

Comparison of MRI-assessed body fat content between lean women with polycystic ovary syndrome (PCOS) and matched controls: less visceral fat with PCOS.

PubMed

Dolfing, Jacoba G; Stassen, Chrit M; van Haard, Paul M M; Wolffenbuttel, Bruce H R; Schweitzer, Dave H

2011-06-01

BACKGROUND Polycystic ovary syndrome (PCOS) is a heterogeneous disorder. However, PCOS has a strong resemblance to the metabolic syndrome, including preponderance of visceral fat deposition. The aim of this study is to compare fat distribution between lean women with PCOS and controls matched for body composition but with regular menstrual cycles and proven fertility. METHODS In this prospective cross-sectional study in a fertility outpatient clinic, 10 Caucasian women with PCOS and 10 controls, all with a BMI between 19 and 25 kg/m(2), were included. Fasting glucose, insulin and C-peptide concentrations, homeostasis model assessment (HOMA), hormonal levels and bioelectrical impedance analysis (BIA) variables were assessed and fat content and ovarian volume determinations were obtained with magnetic resonance imaging (MRI). Multiple axial cross-sections were calculated. RESULTS The age of the PCOS and control groups were [mean (SD)] 28.2 years (2.6) versus 33.7 years (2.3) P < 0.0001, respectively, and both groups were matched for BMI: 21.6 kg/m(2) (1.1) versus 21.8 kg/m(2) (2.1) (ns), fasting glucose, insulin, C-peptide, HOMA-insulin resistance (IR) levels and BIA parameters. PCOS cases had higher ovarian volumes and less visceral fat compared with controls. CONCLUSIONS Lean women with PCOS have higher MRI-determined ovarian volumes and less visceral fat content when compared with control women.

Clinical, endocrine and metabolic effects of metformin added to ethinyl estradiol-cyproterone acetate in non-obese women with polycystic ovarian syndrome: a randomized controlled study.

PubMed

Elter, Koray; Imir, Gonca; Durmusoglu, Fatih

2002-07-01

Oral contraceptive pills (OC) are usually the first choice of treatment for polycystic ovarian syndrome (PCOS), when fertility is not desired. However, they do not improve, or may even further induce impairment of insulin sensitivity, which is already impaired in women with PCOS. In this prospective, randomized study, we analysed the additional benefits of adding metformin to the OC treatment in non-obese women with PCOS. After a baseline work-up including body mass index (BMI), waist:hip ratio (WHR), Ferriman-Gallwey score, ovarian volume, serum gonadotrophin, androgen and sex hormone-binding globulin (SHBG) levels, and fasting lipid, glucose and insulin levels, 40 non-obese women with PCOS were assigned either to the OC or to the OC + metformin treatment by computer-assisted randomization. At the end of the 4 month follow-up period, subjects were re-evaluated. The two groups were similar at baseline. After treatment, women in the OC + metformin group had significant decreases in BMI and WHR, and a significant increase in insulin sensitivity, in contrast to those in the OC group, who had insignificant changes in these parameters. Adding metformin also caused significant improvements in serum androstenedione and SHBG levels compared with the OC treatment alone. Adding metformin to the OC treatment may improve the insulin sensitivity, and may further suppress the hyperandrogenaemia in non-obese women with PCOS.

The effect of weight loss on anti-Müllerian hormone levels in overweight and obese women with polycystic ovary syndrome and reproductive impairment.

PubMed

Thomson, R L; Buckley, J D; Moran, L J; Noakes, M; Clifton, P M; Norman, R J; Brinkworth, G D

2009-08-01

Anti-Müllerian hormone (AMH) has been proposed as a clinical predictor of improvements in reproductive function following weight loss in overweight and obese women with polycystic ovary syndrome (PCOS). This study aimed to assess whether baseline and/or change in AMH levels with weight loss predict improvements in reproductive function in overweight and obese women with PCOS. Fifty-two overweight and obese women with PCOS and reproductive impairment (age 29.8 +/- 0.8 years, BMI 36.5 +/- 0.7 kg/m(2)) followed a 20-week weight loss programme. AMH, weight, menstrual cyclicity and ovulatory function were assessed at baseline and post-intervention. Participants who responded with improvements in reproductive function (n = 26) had lower baseline AMH levels (23.5 +/- 3.7 versus 32.5 +/- 2.9 pmol/l; P = 0.03) and experienced greater weight loss (-11.7 +/- 1.2 versus -6.4 +/- 0.9 kg; P = 0.001) compared with those who did not respond (n = 26). Logistic regression analysis showed that weight loss and baseline AMH were independently related to improvements in reproductive function (P = 0.002 and P = 0.013, respectively). AMH levels did not change with weight loss in both responders and non-responders. In overweight and obese women with PCOS and reproductive dysfunction, a 20-week weight loss intervention resulted in improvements in reproductive function but no change in AMH levels. ACTRN12606000198527.

[Which ovarian stimulation to which women: The polycystic ovary syndrome (PCOS)].

PubMed

Merviel, P; Bouée, S; Ménard, M; Le Martelot, M-T; Roche, S; Lelièvre, C; Chabaud, J-J; Jacq, C; Drapier, H; Beauvillard, D

2017-11-01

Polycystic ovarian syndrome (PCOS) is a frequent pathology in the young woman, linking infertility to a metabolic disease. Initial support will include a plan (in the case of overweight or obesity) to lose at least 5 to 10% of the weight. Subsequently, clomiphene citrate is the first treatment for ovulation induction with pregnancy rates of 40 to 80% after 6 cycles. If there is resistance to clomiphene citrate, the choice will be between the ovarian drilling (50-60% of pregnancy in the year following, including the half spontaneous) or ovarian stimulation with gonadotropins. The risk of ovarian stimulation in these women is hyperstimulation and multiple pregnancies. We also discuss the place of the GnRH pulsatile administration, insulin-sensitizers, in vitro fertilization and in vitro maturation in these women. Once infertility support, these women should be long-term followed because of the neoplasic and cardiovascular risks they present. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Expression of 11beta-hydroxysteroid dehydrogenase 1 and 2 in subcutaneous adipose tissue of lean and obese women with and without polycystic ovary syndrome.

PubMed

Svendsen, P F; Madsbad, S; Nilas, L; Paulsen, S K; Pedersen, S B

2009-11-01

To investigate the expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and 2 and hexose-6-phosphate dehydrogenase (H6PDH) mRNA in subcutaneous abdominal tissue from lean and obese women with and without polycystic ovary syndrome (PCOS), and to investigate the association between these enzymes and different measures of insulin sensitivity. Cross-sectional study. A total of 60 women, 36 women with PCOS, 17 lean (lean PCOS, LP) and 19 obese (obese PCOS, OP) and 24 age- and weight-matched control women, 8 lean (lean controls, LC) and 16 obese (obese controls, OC). Subcutaneous adipose tissue was collected from the abdomen. Peripheral insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp and determined as glucose disposal rate and insulin sensitivity index. Whole-body insulin sensitivity was calculated using homeostasis model assessment insulin resistance index. Body composition was evaluated by dual X-ray absorptiometry. Adipose mRNA expression of leptin and adiponectin were determined by real-time PCR. Polycystic ovary syndrome (P<0.05) and obesity (P<0.05) were independently associated with increased expression of 11beta-HSD1 mRNA. The subgroups LP and OC had increased 11beta-HSD1 and 11beta-HSD2 mRNA expression compared with LC (P<0.05, P<0.05). There were no effects of PCOS or obesity on11beta-HSD2 or H6PDH mRNA expression. Decreased peripheral insulin sensitivity (P<0.001) and increased upper body fat distribution (P<0.01) were associated with increased expression of 11beta-HSD1, but neither 11beta-HSD2 nor H6PDH. Polycystic ovary syndrome and obesity are independently associated with increased expression of 11beta-HSD1. This may lead to increased conversion of cortisone to cortisol in the peripheral adipose tissue and subsequently increased glucocorticoid activity. Decreased peripheral insulin sensitivity and central obesity was associated with increased expression of 11beta-HSD1.

What do we know about metabolic syndrome in adolescents with PCOS?

PubMed Central

Cırık, Derya Akdağ; Dilbaz, Berna

2014-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women that manifests itself with a variety of features. For this reason, three different diagnostic criteria have been introduced. For adults, the National Institutes of Health Conference (NIH) criteria, which consists of hyperandrogenism and oligo-anovulation, is the most widely used. Symptoms of PCOS usually start with puberty and may overlap with normal pubertal development. Hormonal fluctuations during this period make the diagnosis of PCOS more difficult. Until now, there is no validated diagnostic criteria for PCOS in adolescents. Although menstrual disorders and cosmetic problems are the most common complaints of adolescents with PCOS, patients should also be evaluated for the potential risk for insulin resistance, obesity, subclinical atherosclerosis, diabetes, metabolic syndrome and cardiovascular disease. Obesity is the most prominent predictor of metabolic syndrome. As the incidence of obesity is increasing both in childhood and adolescence, governments will be faced with a social and economic burden in the future. Adolescents with PCOS are more obese than normal adolescents and have an increased risk of metabolic syndrome. It is suggested that abdominal adiposity increases the risk of metabolic syndrome by inducing various cytokine secretions. Although there is no consensus on metabolic syndrome criteria in the adolescent period, International Diabetes Federation (IDF) criteria may be used for children older than 10 years. Various clinical and metabolic markers are investigated for the prediction of metabolic syndrome in the literature. Waist circumference, serum triglycerides and androgens are the suspected predictors of metabolic syndrome. The prevention of abdominal adiposity and the early diagnosis of PCOS in adolescence should be the main target for the prevention of metabolic syndrome. Clinicians should investigate adolescents with PCOS for metabolic and

What do we know about metabolic syndrome in adolescents with PCOS?

PubMed

Cırık, Derya Akdağ; Dilbaz, Berna

2014-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women that manifests itself with a variety of features. For this reason, three different diagnostic criteria have been introduced. For adults, the National Institutes of Health Conference (NIH) criteria, which consists of hyperandrogenism and oligo-anovulation, is the most widely used. Symptoms of PCOS usually start with puberty and may overlap with normal pubertal development. Hormonal fluctuations during this period make the diagnosis of PCOS more difficult. Until now, there is no validated diagnostic criteria for PCOS in adolescents. Although menstrual disorders and cosmetic problems are the most common complaints of adolescents with PCOS, patients should also be evaluated for the potential risk for insulin resistance, obesity, subclinical atherosclerosis, diabetes, metabolic syndrome and cardiovascular disease. Obesity is the most prominent predictor of metabolic syndrome. As the incidence of obesity is increasing both in childhood and adolescence, governments will be faced with a social and economic burden in the future. Adolescents with PCOS are more obese than normal adolescents and have an increased risk of metabolic syndrome. It is suggested that abdominal adiposity increases the risk of metabolic syndrome by inducing various cytokine secretions. Although there is no consensus on metabolic syndrome criteria in the adolescent period, International Diabetes Federation (IDF) criteria may be used for children older than 10 years. Various clinical and metabolic markers are investigated for the prediction of metabolic syndrome in the literature. Waist circumference, serum triglycerides and androgens are the suspected predictors of metabolic syndrome. The prevention of abdominal adiposity and the early diagnosis of PCOS in adolescence should be the main target for the prevention of metabolic syndrome. Clinicians should investigate adolescents with PCOS for metabolic and

Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women.

PubMed

Teede, Helena J; Joham, Anju E; Paul, Eldho; Moran, Lisa J; Loxton, Deborah; Jolley, Damien; Lombard, Catherine

2013-08-01

Polycystic ovary syndrome (PCOS) affects 6-18% of women. The natural history of weight gain in women with PCOS has not been well described. Here we aimed to examine longitudinal weight gain in women with and without PCOS and to assess the association between obesity and PCOS prevalence. The observational study was set in the general community. Participants were women randomly selected from the national health insurance scheme (Medicare) database. Mailed survey data were collected by the Australian Longitudinal Study on Women's Health. Data from respondents to survey 4, aged 28-33 years (2006, n = 9,145) were analyzed. The main outcome measures were PCOS prevalence and body mass index (BMI). Self-reported PCOS prevalence was 5.8% (95% CI: 5.3%-6.4%). Women reporting PCOS had higher weight, mean BMI [2.5 kg/m(2) (95% CI: 1.9-3.1)], and greater 10-year weight gain [2.6 kg (95% CI: 1.2-4.0)]. BMI was the strongest correlate of PCOS status with every BMI increment increasing the risk of reporting PCOS by 9.2% (95% CI: 6%-12%). This community based observational study with longitudinal reporting of weight shows that weight, BMI, and 10-year weight gain were higher in PCOS. We report the novel finding that obesity and greater weight gain are significantly associated with PCOS status. Considering the prevalence, major health and economic burden of PCOS, the increasing weight gain in young women, and established benefits of weight loss, these results have major public health implications. Copyright © 2012 The Obesity Society.

Low Starch/Low Dairy Diet Results in Successful Treatment of Obesity and Co-Morbidities Linked to Polycystic Ovary Syndrome (PCOS).

PubMed

Phy, Jennifer L; Pohlmeier, Ali M; Cooper, Jamie A; Watkins, Phillip; Spallholz, Julian; Harris, Kitty S; Berenson, Abbey B; Boylan, Mallory

2015-04-01

Polycystic Ovary Syndrome (PCOS) affects approximately 15% of reproductive-age women and increases risk of insulin resistance, type 2 diabetes mellitus, cardiovascular disease, cancer and infertility. Hyperinsulinemia is believed to contribute to or worsen all of these conditions, and increases androgens in women with PCOS. Carbohydrates are the main stimulators of insulin release, but research shows that dairy products and starches elicit greater postprandial insulin secretion than non-starchy vegetables and fruits. The purpose of this study was to determine whether an 8-week low-starch/low-dairy diet results in weight loss, increased insulin sensitivity, and reduced testosterone in women with PCOS. Prospective 8-week dietary intervention using an ad libitum low starch/low dairy diet in 24 overweight and obese women (BMI ≥ 25 kg/m 2 and ≤ 45 kg/m 2 ) with PCOS. Diagnosis of PCOS was based on the Rotterdam criteria. Weight, BMI, Waist Circumference (WC), Waist-to-Height Ratio (WHtR), fasting and 2-hour glucose and insulin, homeostasis model assessment of Insulin Resistance (HOMA-IR), HbA1c, total and free testosterone, and Ferriman-Gallwey scores were measured before and after the 8-week intervention. There was a reduction in weight (-8.61 ± 2.34 kg, p<0.001), BMI (-3.25 ± 0.88 kg/m 2 , p<0.001), WC (-8.4 ± 3.1 cm, p<0.001), WHtR (-0.05 ± 0.02 inches, p<0.001), fasting insulin (-17.0 ± 13.6 μg/mL, p<0.001) and 2-hour insulin (-82.8 ± 177.7 μg/mL, p=0.03), and HOMA-IR (-1.9 ± 1.2, p<0.001) after diet intervention. Total testosterone (-10.0 ± 17.0 ng/dL, p=0.008), free testosterone (-1.8 pg/dL, p=0.043) and Ferriman-Gallwey scores (-2.1 ± 2.7 points (p=0.001) were also reduced from pre- to post-intervention. An 8-week low-starch/low-dairy diet resulted in weight loss, improved insulin sensitivity and reduced testosterone in women with PCOS.

Low Starch/Low Dairy Diet Results in Successful Treatment of Obesity and Co-Morbidities Linked to Polycystic Ovary Syndrome (PCOS)

PubMed Central

Phy, Jennifer L.; Pohlmeier, Ali M.; Cooper, Jamie A.; Watkins, Phillip; Spallholz, Julian; Harris, Kitty S.; Berenson, Abbey B.; Boylan, Mallory

2015-01-01

Background Polycystic Ovary Syndrome (PCOS) affects approximately 15% of reproductive-age women and increases risk of insulin resistance, type 2 diabetes mellitus, cardiovascular disease, cancer and infertility. Hyperinsulinemia is believed to contribute to or worsen all of these conditions, and increases androgens in women with PCOS. Carbohydrates are the main stimulators of insulin release, but research shows that dairy products and starches elicit greater postprandial insulin secretion than non-starchy vegetables and fruits. The purpose of this study was to determine whether an 8-week low-starch/low-dairy diet results in weight loss, increased insulin sensitivity, and reduced testosterone in women with PCOS. Methods Prospective 8-week dietary intervention using an ad libitum low starch/low dairy diet in 24 overweight and obese women (BMI ≥ 25 kg/m2 and ≤ 45 kg/m2) with PCOS. Diagnosis of PCOS was based on the Rotterdam criteria. Weight, BMI, Waist Circumference (WC), Waist-to-Height Ratio (WHtR), fasting and 2-hour glucose and insulin, homeostasis model assessment of Insulin Resistance (HOMA-IR), HbA1c, total and free testosterone, and Ferriman-Gallwey scores were measured before and after the 8-week intervention. Results There was a reduction in weight (−8.61 ± 2.34 kg, p<0.001), BMI (−3.25 ± 0.88 kg/m2, p<0.001), WC (−8.4 ± 3.1 cm, p<0.001), WHtR (−0.05 ± 0.02 inches, p<0.001), fasting insulin (−17.0 ± 13.6 μg/mL, p<0.001) and 2-hour insulin (−82.8 ± 177.7 μg/mL, p=0.03), and HOMA-IR (−1.9 ± 1.2, p<0.001) after diet intervention. Total testosterone (−10.0 ± 17.0 ng/dL, p=0.008), free testosterone (−1.8 pg/dL, p=0.043) and Ferriman-Gallwey scores (−2.1 ± 2.7 points (p=0.001) were also reduced from pre- to post-intervention. Conclusion An 8-week low-starch/low-dairy diet resulted in weight loss, improved insulin sensitivity and reduced testosterone in women with PCOS. PMID:26225266

Effect of a low-starch/low-dairy diet on fat oxidation in overweight and obese women with polycystic ovary syndrome.

PubMed

Pohlmeier, Ali M; Phy, Jennifer L; Watkins, Phillip; Boylan, Mallory; Spallholz, Julian; Harris, Kitty S; Cooper, Jamie A

2014-11-01

Polycystic ovary syndrome (PCOS) affects between 4%-18% of reproductive-aged women and is associated with increased risk of obesity and obesity-related disease. PCOS is associated with hyperinsulinemia, which is known to impair fat oxidation. Research shows that carbohydrates from dairy and starch-based foods cause greater postprandial insulin secretion than carbohydrates from nonstarchy vegetables and fruits. The purpose of this study was to determine whether an ad libitum 8-week low-starch/low-dairy diet would improve fasting and postprandial fat oxidation after a high saturated fat liquid meal (HSFLM) in overweight and obese women with PCOS. Prospective 8-week dietary intervention using a low-starch/low-dairy diet in 10 women (body mass index ≥25 kg/m(2) and ≤45 kg/m(2)) with PCOS. Indirect calorimetry was used at fasting and for 5 h following consumption of the HSFLM to determine respiratory exchange ratio (RER), macronutrient oxidation, and energy expenditure (EE) at week 0 and week 8. Participants had a reduction in body weight (-8.1 ± 1.8 kg, p < 0.05) and fasting insulin (-19.5 ± 8.9 μg/mL, p < 0.05) after dietary intervention; however, these were not significantly correlated with improved fat oxidation. There was a reduction in fasting RER, and fasting and postprandial carbohydrate oxidation, and an increase in fasting and postprandial fat oxidation after adjusting for body weight. There was also significant difference in incremental area under the curve from pre- to post-diet for fat (0.06 ± 0.00 g/kg per 5 h; p < 0.001) and carbohydrate oxidation (-0.29 ± 0.06 g/kg per 5 h; p < 0.001), but not for RER or EE. In conclusion, an 8-week low-starch/low-dairy diet increased fat oxidation in overweight and obese women with PCOS.

Effect of a Low Starch/Low Dairy Diet on Fat Oxidation in Overweight and Obese Women with Polycystic Ovary Syndrome

PubMed Central

Pohlmeier, Ali M.; Phy, Jennifer L.; Watkins, Phillip; Boylan, Mallory; Spallholz, Julian; Harris, Kitty S.; Cooper, Jamie A.

2014-01-01

Background Polycystic ovary syndrome (PCOS) affects between 4%- 18% of reproductive-aged women and is associated with increased risk of obesity and obesity-related disease. PCOS is associated with hyperinsulinemia which is known to impair fat oxidation. Research shows that carbohydrates from dairy and starch-based foods cause greater postprandial insulin secretion than carbohydrates from non-starchy vegetables and fruits. Objective To determine whether an ad libitum 8-week low starch/low dairy diet would improve fasting and postprandial fat oxidation after a high saturated fat liquid meal (HSFLM) in overweight and obese women with PCOS. Methods Prospective 8-week dietary intervention using a low starch/low dairy diet in 10 women (BMI ≥25kg/m2 and ≤45kg/m2) with PCOS. Indirect calorimetry was used at fasting and for 5 hours following consumption of the HSFLM to determine respiratory exchange ratio (RER), macronutrient oxidation, and energy expenditure (EE) at week 0 and week 8. Results Participants had a reduction in body weight (−8.1±1.8kg, p<0.05) and fasting insulin (−19.5±8.9μg/mL, p<0.05) after dietary intervention; however, these were not significantly correlated with improved fat oxidation. There was a reduction in fasting RER, and fasting and postprandial CHO oxidation, and an increase in fasting and postprandial fat oxidation after adjusting for body weight. There was also significant difference in incremental area under the curve (iAUC) from pre- to post-diet for fat (0.06±0.00 g/kg/5hour; p<0.001) and carbohydrate oxidation (−0.29±0.06 g/kg/5hour; p<0.001), but not for RER or EE. Conclusions An 8-week low starch/low dairy diet increased fat oxidation in overweight and obese women with PCOS. PMID:25109619

Clinical characteristics in Taiwanese women with polycystic ovary syndrome

PubMed Central

2015-01-01

Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age. PMID:26473107

Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS

PubMed Central

Sarwer, David B.; Allison, Kelly C.; Milman, Lauren; Kris-Etherton, Penny M.; Kunselman, Allen R.; Stetter, Christy M.; Williams, Nancy I.; Gnatuk, Carol L.; Estes, Stephanie J.; Fleming, Jennifer; Coutifaris, Christos; Legro, Richard S.

2016-01-01

Context: Polycystic ovary syndrome (PCOS) is associated with reduced health-related quality of life (HRQOL) and increased prevalence of depressive and anxiety disorders. The impact of PCOS-specific treatments on these co-morbidities is unclear. Objective: To assess the impact of weight loss and decreasing hyperandrogenism on HRQOL and mood and anxiety disorders in women with PCOS. Design/Setting/Participants: A secondary analysis of a randomized controlled trial (OWL-PCOS) of preconception treatment conducted at two academic centers in women (age, 18–40 years; body mass index, 27–42 kg/m2) with PCOS defined by Rotterdam criteria. Intervention: Continuous oral contraceptive pill (OCP) or intensive lifestyle intervention or the combination (Combined) for 16 weeks. Main Outcome Measure(s): Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ. Results: The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ. All three interventions resulted in significant improvement in the general health score on the SF-36. Both the OCP and Combined groups showed improvements in all domains of the PCOSQ (P < .01) compared to baseline scores. The Combined group had significant improvements in the weight, body hair, and infertility domains compared to a single treatment group (P < .05). In a linear regression model, change in weight correlated with improvements in the weight domain (P < .001) and physical well-being (P < .02), change in T correlated with improvements in the hair domain (P < .001), and change in both weight and T correlated with the infertility (P < .001) and menstrual domains (P < .05). Conclusions: Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life, depressive symptoms, and anxiety disorders, and combined therapies offer further benefits in overweight/obese

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

PubMed Central

2018-01-01

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770

The effects of old, new and emerging medicines on metabolic aberrations in PCOS

PubMed Central

Bargiota, Alexandra

2012-01-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age that is associated with significant adverse short- and long-term health consequences. Multiple metabolic aberrations, such as insulin resistance (IR) and hyperinsulinaemia, high incidence of impaired glucose tolerance, visceral obesity, inflammation and endothelial dysfunction, hypertension and dyslipidemia are associated with the syndrome. Assessing the metabolic aberrations and their long term health impact in women with PCOS is challenging and becomes more important as therapeutic interventions currently available for the management of PCOS are not fully able to deal with all these consequences. Current therapeutic management of PCOS has incorporated new treatments resulting from the better understanding of the pathophysiology of the syndrome. The aim of this review is to summarize the effect of old, new and emerging therapies used in the management of PCOS, on the metabolic aberrations of PCOS PMID:23148192

Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.

PubMed

Cordeiro, Fernanda Bertuccez; Cataldi, Thaís Regiani; do Vale Teixeira da Costa, Lívia; de Lima, Camila Bruna; Stevanato, Juliana; Zylbersztejn, Daniel Suslik; Ferreira, Christina Ramires; Eberlin, Marcos Nogueira; Cedenho, Agnaldo Pereira; Turco, Edson Guimarães Lo

2015-01-01

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation. Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment. The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR). These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Improvement in Quality of Life Questionnaire Measures (PCOSQ) in Obese Adolescent Females with PCOS treated with Lifestyle Changes and Oral Contraceptives, with or without Metformin

PubMed Central

Harris-Glocker, Miranda; Davidson, Kristin; Kochman, Lynda; Guzick, David; Hoeger, Kathleen

2013-01-01

We studied the effect of metformin or placebo in a lifestyle modification program (LSM) combined with oral contraceptives (OC) on quality of life parameters measured by the PCOS questionnaire (PCOSQ) in obese adolescent women with validated PCOS. The quality of life indicators were measured at baseline and conclusion for 5 domains on the PCOSQ, with equal improvement in scores in both placebo and Metformin groups, suggesting metformin addition does not add improvement to quality of life measures above those observed with lifestyle modification and oral contraceptive treatment. PMID:19781696

Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome.

PubMed

Gambineri, Alessandra; Pelusi, Carla; Genghini, Silvia; Morselli-Labate, Antonio Maria; Cacciari, Mauro; Pagotto, Uberto; Pasquali, Renato

2004-02-01

Hyperandrogenism, hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome (PCOS), contributing in different ways to the clinical expression of the syndrome. Weight loss is beneficial, but the additional administration of insulin-lowering drugs, such as metformin, and antiandrogens may produce further benefits, due to their different spectrum of action. The effects of long-term metformin and flutamide, an antiandrogen drug, added alone or in combination with a low-calorie diet, on body weight and fat distribution, androgens, metabolic parameters and clinical status in obese women with PCOS were investigated. Forty obese women with PCOS were enrolled in the study. After a 1-month diet, according to single-blind design, the patients were allocated to treatment with placebo, metformin (850 mg/orally, twice daily), flutamide (250 mg/orally, twice daily) or metformin (850 mg/orally, twice daily) + flutamide (250 mg/orally, twice daily) for the following 6 months, while continuing hypocaloric dieting. At baseline and at the end of the study, sex hormone, SHBG, lipid, insulin and insulin sensitivity determinations were evaluated. At the same time, clinical parameters such as anthropometry, total (TAT), visceral (VAT) and subcutaneous (SAT) adipose tissue, hirsutism and menses were also measured. We found that, in obese PCOS women, following a hypocaloric diet the addition of metformin, flutamide or the combined metformin + flutamide treatment had some specific additional favourable effects with respect to the low-calorie diet alone. In particular, flutamide treatment seemed to add a significant effect in decreasing visceral fat, androstenedione, DHEA-S, total and low density lipoprotein (LDL) cholesterol and in improving hirsutism. Conversely, metformin had significant benefits on the menstrual status. The two drugs showed an additive effect in reducing testosterone concentrations and a synergistic effect in

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts.

PubMed

Ozgen Saydam, Basak; Has, Arzu Ceylan; Bozdag, Gurkan; Oguz, Kader Karli; Yildiz, Bulent Okan

2017-07-01

To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls. Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed. Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p < 0.05 for both) whereas lean PCOS and controls did not show a significant difference. Secondary analyses of regional brain volumes showed decreases in GMV of the caudate nucleus, ventral diencephalon and hippocampus in obese PCOS compared to obese controls (p < 0.05 for all), whereas lean patients with PCOS had lower GMV in the amygdala than lean controls (p < 0.05). No significant relations were detected between structural differences and measured hormone levels at baseline or during MTT. This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.

Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses.

PubMed

Harborne, Lyndal R; Sattar, Naveed; Norman, Jane E; Fleming, Richard

2005-08-01

Metformin treatment of women with polycystic ovary syndrome (PCOS) is widespread, as determined by studies with diverse patient populations. No comparative examination of weight changes or metabolite responses to different doses has been reported. The aim of this study was to determine whether different doses of metformin (1500 or 2550 mg/d) would have different effects on body weight, circulating hormones, markers of inflammation, and lipid profiles. The study included prospective cohorts randomized to two doses of metformin. The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics. The patients studied were obese (body mass index, 30 to <37 kg/m2; n = 42) and morbidly obese (body mass index, > or =37 kg/m2; n = 41) women with PCOS. Patients were randomized to two doses of metformin, and parameters were assessed after 4 and 8 months. The main outcome measures were changes in body mass, circulating hormones, markers of inflammation, and lipid profiles. Intention to treat analyses showed significant weight loss in both dose groups. Only the obese subgroup showed a dose relationship (1.5 and 3.6 kg in 1500- and 2550-mg groups, respectively; P = 0.04). The morbidly obese group showed similar reductions (3.9 and 3.8 kg) in both groups. Suppression of androstenedione was significant with both metformin doses, but there was no clear dose relationship. Generally, beneficial changes in lipid profiles were not related to dose. Weight loss is a feature of protracted metformin therapy in obese women with PCOS, with greater weight reduction potentially achievable with higher doses. Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin.

Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

PubMed Central

Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

2015-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. PMID:26124830

Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women.

PubMed

Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

2015-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS.

PubMed

Zhang, Jinxia; Fan, Ping; Liu, Hongwei; Bai, Huai; Wang, Ying; Zhang, Feng

2012-08-01

What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the

Depression symptoms and body dissatisfaction association among polycystic ovary syndrome women.

PubMed

Pastore, Lisa M; Patrie, James T; Morris, Wendy L; Dalal, Parchayi; Bray, Megan J

2011-10-01

One publication reported that lower body satisfaction and lower education were independent predictors of depression in polycystic ovary syndrome (PCOS) in women. This study replicates that analysis using different instruments, and adds androgen levels to the model. Cross-sectional analysis of questionnaires (Quick Inventory of Depressive Symptomatology-Self-Report, Body Esteem Scale) and serum androgens from a community cohort with (n=94) and without (n=96) PCOS, matched by BMI category. Non-parametric tests, Spearman correlations, and negative binomial regression models were analyzed. Depression symptoms were common (40-60% in lean, overweight and obese BMI categories) in the PCOS cohort, albeit generally of mild severity. The PCOS women had similar depression symptom severity (P>.20) and similar body dissatisfaction (P≥.25) as the regularly cycling women in total and stratified by BMI category. In both the PCOS and non-PCOS cohorts, depression symptom severity was positively correlated with dissatisfaction with physical appearance and physical conditioning (P<.02). Body dissatisfaction (especially perception of physical conditioning) was strongly associated with more severe depression symptoms in non-obese PCOS women (BMI<30, P<.04) before and after controlling for age, testosterone and free testosterone. In contrast, for obese women with PCOS, depression was unrelated to body dissatisfaction after controlling for age. Among non-obese PCOS women, their subjective body image was strongly associated with the severity of their depression symptoms. Most of the obese PCOS cohort had low body satisfaction and depression symptoms, therefore individual differences in the body dissatisfaction scores were not helpful in identifying depression symptom severity. Neither testosterone nor free testosterone was associated with depression symptom severity in PCOS women after controlling for body dissatisfaction and age. Copyright © 2011 Elsevier Inc. All rights reserved.

Depression Symptoms and Body Dissatisfaction Association Among Polycystic Ovary Syndrome Women

PubMed Central

Pastore, Lisa M.; Patrie, James T.; Morris, Wendy L.; Dalal, Parchayi; Bray, Megan J

2011-01-01

Objective One publication reported that lower body satisfaction and lower education were independent predictors of depression in polycystic ovary syndrome (PCOS) women. This study replicates that analysis using different instruments, and adds androgen levels to the model. Methods Cross-sectional analysis of questionnaires (Quick Inventory of Depressive Symptomatology-Self-Report, Body Esteem Scale) and serum androgens from a community cohort with (n=94) and without (n=96) PCOS, matched by BMI category. Non-parametric tests, Spearman correlations, and negative binomial regression models were analyzed. Results Depression symptoms were common (40–60% in lean, overweight and obese BMI categories) in the PCOS cohort, albeit generally of mild severity. The PCOS women had similar depression symptom severity (P > 0.20) and similar body dissatisfaction (P ≥ 0.25) as the regularly cycling women in total and stratified by BMI category. In both the PCOS and non-PCOS cohorts, depression symptom severity was positively correlated with dissatisfaction with physical appearance and physical conditioning (P < 0.02). Body dissatisfaction (especially perception of physical conditioning) was strongly associated with more severe depression symptoms in non-obese PCOS women (BMI<30, P < 0.04) before and after controlling for age, testosterone and free testosterone. In contrast, for obese women with PCOS, depression was unrelated to body dissatisfaction after controlling for age. Conclusions Among non-obese PCOS women, their subjective body image was strongly associated with the severity of their depression symptoms. Most of the obese PCOS cohort had low body satisfaction and depression symptoms, therefore individual differences in the body dissatisfaction scores were not helpful in identifying depression symptom severity. Neither testosterone nor free testosterone were associated with depression symptom severity in PCOS women after controlling for body dissatisfaction and age. US

Serum 25-Hydroxyvitamin D Levels, phosphoprotein enriched in diabetes gene product (PED/PEA-15) and leptin-to-adiponectin ratio in women with PCOS.

PubMed

Savastano, Silvia; Valentino, Rossella; Di Somma, Carolina; Orio, Francesco; Pivonello, Claudia; Passaretti, Federica; Brancato, Valentina; Formisano, Pietro; Colao, Annamaria; Beguinot, Francesco; Tarantino, Giovanni

2011-11-23

Polycystic ovary syndrome (PCOS) is frequently associated with hypovitaminosis D. Vitamin D is endowed with pleiotropic effects, including insulin resistance (IR) and apoptotic pathway. Disruption of the complex mechanism that regulated ovarian apoptosis has been reported in PCOS. Phosphoprotein enriched in diabetes gene product (PED/PEA-15), an anti-apoptotic protein involved in type 2 diabetes mellitus (T2DM), is overexpressed in PCOS women, independently of obesity. Leptin-to-adiponectin ratio (L/A) is a biomarker of IR and low-grade inflammation in PCOS. The aim of the study was to investigate the levels of 25-hydroxy vitamin D (25(OH)D), and L/A, in association with PED/PEA-15 protein abundance, in both lean and overweight/obese (o/o) women with PCOS. PED/PEA-15 protein abundance and circulating levels of 25(OH)D, L/A, sex hormone-binding globulin, and testosterone were evaluated in 90 untreated PCOS patients (25 ± 4 yrs; range 18-34) and 40 healthy controls age and BMI comparable, from the same geographical area. FAI (free androgen index) and the homeostasis model assessment of insulin resistance (HoMA-IR) index were calculated. In o/o PCOS, 25(OH)D levels were significantly lower, and L/A values were significantly higher than in lean PCOS (p < 0.001), while there were no differences in PED/PEA-15 protein abundance. An inverse correlation was observed between 25(OH)D and BMI, PED/PEA-15 protein abundance, insulin, HoMA-IR, FAI (p < 0.001), and L/A (p < 0.05). At the multivariate analysis, in o/o PCOS L/A, insulin and 25(OH)D were the major determinant of PED/PEA-15 protein abundance (β = 0.45, β = 0.41, and β = -0.25, respectively). Lower 25(OH)D and higher L/A were associated to PED/PEA-15 protein abundance in PCOS, suggesting their involvement in the ovarian imbalance between pro-and anti-apoptotic mechanisms, with high L/A and insulin and low 25(OH)D levels as the main determinants of PED/PEA-15 protein variability. Further studies, involving also

Plasma visfatin level in lean women with PCOS: relation to proinflammatory markers and insulin resistance.

PubMed

Gen, Ramazan; Akbay, Esen; Muslu, Necati; Sezer, Kerem; Cayan, Filiz

2009-04-01

The present study was undertaken to investigate the association between plasma visfatin concentrations and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) in company with several metabolic parameters in lean women with polycystic ovary syndrome (PCOS). The study group consisted of 21 lean women with PCOS (BMI 20.74 +/- 1.74 kg/m(2)) and 15 healthy, normally menstruating women (BMI 20.85 +/- 2.08 kg/m(2) control group). PCOS was defined according to the Rotterdam criteria. Visfatin, IL-6, hsCRP, hyperandrogenism markers and metabolic markers were examined in all PCOS and control women. Plasma visfatin level in the PCOS group was higher than that in the control group. Plasma hsCRP and IL-6 levels in PCOS group were similar with the control group. Plasma visfatin levels were positively associated with total cholesterol, high density lipoprotein, hirsutism score, total testosterone and FAI. Plasma visfatin level was negatively associated with SHBG. However, there were no correlation between plasma visfatin level and IL-6 and hsCRP. In multivariate regression analyses, only FAI and high density lipoprotein-cholesterol (HDL-C) showed a significant association with serum visfatin. Our data indicates that plasma visfatin levels are associated with HDL-C and markers of hyperandrogenism, but it is not associated with proinflammatory markers and insulin resistance in lean women with PCOS.

Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome.

PubMed

Gong, Ping; Shi, Bingwei; Wang, Juan; Cao, Peixia; Diao, Zhenyu; Wang, Yuji; Hu, Yali; Li, Shuping

2018-02-15

This study aimed to investigate the Th1/Th2 cells in peripheral blood of PCOS patients, and assess the potential correlation between Th1/Th2 imbalance and obesity. Thirty-nine PCOS patients and 23 age-matched controls were enrolled. The PBMCs were obtained before pharmacological intervention in women with or without PCOS. The profiles of Th1 (IFN-γ) and Th2 (IL-4) cytokines of CD3 + CD - T lymphocyte subsets were analyzed by flow cytometry. Plasma sex hormones including E 2 , T, FSH, LH, and FINS, FPG were measured, together with BMI, WC, LH/FSH, E 2 /T and HOMA-IR index being calculated. Association between Th1/Th2 imbalance and BMI, WC were evaluated. The proportion of Th1 cells and Th1/Th2 ratio were significantly higher in PCOS patients than those in controls, accompanied by elevated T, LH, LH/FSH, FINS, HOMA-IR index and reduced E 2 /T. The Th1/Th2 ratio was increased when BMI and WC were enhanced in PCOS. Moreover, the significant difference of Th1/Th2 ratio was observed between WC subgroups of PCOS. It is concluded that Th1 type immunity is predominant in systemic immunization of PCOS patients. Th1/Th2 immune imbalance is connected with obesity, especially abdominal obesity, and may be one of the underlying mechanism for the pathogenesis of PCOS.

Does Metformin Treatment During Pregnancy Modify the Future Metabolic Profile in Women With PCOS?

PubMed

Underdal, Maria Othelie; Stridsklev, Solhild; Oppen, Ingrid Hennum; Høgetveit, Kristin; Andersen, Marianne Skovsager; Vanky, Eszter

2018-06-01

Worldwide, metformin is prescribed to improve pregnancy outcome in polycystic ovary syndrome (PCOS). Metformin may also benefit future health by modulating increased metabolic stress during pregnancy. To investigate whether metformin during pregnancy modified future metabolic health in women with PCOS. Follow-up study of a randomized controlled trial that compared metformin with placebo in women with PCOS. Mean follow-up period was 7.7 years (range, 5 to 11 years). Three university hospitals, seven local hospitals, and one gynecological specialist practice. Women with PCOS according to Rotterdam criteria; all former participants in the Metformin in Pregnant PCOS Women Study. Metformin 2000 mg daily or placebo from first trimester to delivery in the original study. No intervention in the present follow-up study. Main outcome measure was weight gain in the follow-up period. Weight, body mass index (BMI), waist and hip circumferences, and blood pressure (BP) were registered. Body composition was assessed by bioelectrical impedance analysis, and fasting lipids, glucose, and insulin were analyzed. Of 239 invited women, 131 (55%) participated in the follow-up. Weight gain was similar in women given metformin (2.1 ± 10.5 kg) and women given placebo (1.8 ± 11.2 kg) at 7.7 years' follow-up after pregnancy (P = 0.834). No difference was found in BMI, waist/hip ratio, BP, body composition, lipids, glucose and insulin levels, or prevalence of metabolic syndrome at follow-up between those treated with metformin and those treated with placebo during pregnancy. Metformin treatment during pregnancy did not influence the metabolic profile in women with PCOS at 7.7 years of follow-up.

Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress.

PubMed

Macut, D; Simic, T; Lissounov, A; Pljesa-Ercegovac, M; Bozic, I; Djukic, T; Bjekic-Macut, J; Matic, M; Petakov, M; Suvakov, S; Damjanovic, S; Savic-Radojevic, A

2011-07-01

To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was significantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also significantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Associations of menstrual cycle irregularities with age, obesity and phenotype in patients with polycystic ovary syndrome.

PubMed

Panidis, Dimitrios; Tziomalos, Konstantinos; Papadakis, Efstathios; Chatzis, Panagiotis; Kandaraki, Eleni A; Tsourdi, Elena A; Macut, Djuro; Bjekic-Macut, Jelica; Marthopoulos, Apostolos; Katsikis, Ilias

2015-01-01

Limited data suggest that menstrual cycle abnormalities are more pronounced in younger and more obese patients with polycystic ovary syndrome (PCOS). We aimed to evaluate the association between menstrual cycle pattern and age, obesity and PCOS phenotype in a large population of women with PCOS. We studied 1,297 women with PCOS and divided them according to: a) age in ≤ 20, 21-30 and > 30 years old, b) body mass index in normal weight, overweight and obese and c) PCOS phenotype in phenotype 1 (anovulation, hyperandrogenemia and polycystic ovaries), 2 (anovulation and hyperandrogenemia without polycystic ovaries), 3 (hyperandrogenemia and polycystic ovaries without anovulation) and 4 (anovulation and polycystic ovaries without hyperandrogenemia). The proportion of women with regular menstrual cycles progressively increased in the older age groups, being 8.1, 10.5 and 12.7% in women ≤ 20, 21-30 and > 30 years old, respectively (p = 0.037). The proportion of women with regular menstrual cycles did not differ between normal weight and obese women but was higher in overweight women (9.3, 9.4 and 13%, respectively; p = 0.020). The proportion of women with regular cycles alternating with irregular cycles was highest in women with phenotype 4, intermediate in women with phenotype 2 and lowest in women with phenotype 1 (74.3, 69.4 and 61.7%, respectively; p = 0.027). Menstrual cycle pattern is more irregular in women with the "classic" PCOS phenotypes than in phenotype 4 but appears to normalize with ageing. On the other hand, obesity does not appear to have an important effect on menstrual cycle pattern in PCOS.

Subclinical hypothyroidism does not influence the metabolic and hormonal profile of women with PCOS.

PubMed

Trakakis, Eftihios; Pergialiotis, Vasilios; Hatziagelaki, Erifili; Panagopoulos, Periklis; Salloum, Ioannis; Papantoniou, Nikolaos

2017-06-23

Background Subclinical hypothyroidism (SCH) is present in 5%-10% of polycystic ovary syndrome (PCOS) patients. To date, its impact on the metabolic and hormonal profile of those women remains controversial. The purpose of our study is to evaluate the impact of SCH on the glycemic, lipid and hormonal profile of PCOS patients. Materials and methods We conducted a prospective case control study of patients that attended the Department of Gynecological Endocrinology of our hospital. Results Overall, 280 women with PCOS were enrolled during a time period of 7 years (2009-2015). Twenty-one patients (7.5%) suffered from SCH. The anthropometric characteristics were comparable among women with PCOS and those with SCH + PCOS. The prevalence of acne, hirsutism and anovulation did not differ. Significant differences were observed in the 2-h oral glucose tolerance test (OGTT) (p = 0.003 for glucose and p = 0.046 for insulin). The QUICKI, Matsuda and homeostatic model assessment-insulin resistance (HOMA-IR) indices where, however, similar. No difference in serum lipids was observed. Slightly elevated levels of follicle stimulating hormone (FSH) and testosterone were noted. The remaining hormonal parameters remained similar among groups. Similarly, the ovarian volume and the endometrial thickness did not differ. Conclusions The impact of SCH on the metabolic and hormonal profile of PCOS patients seems to be negligible. Future studies are needed in the field and their conduct in a multi-institutional basis seems to be required, given the small prevalence of SCH among women with PCOS.

Ovarian reserve in women of late reproductive age by the method of treatment of PCOS.

PubMed

Beltadze, Ketevan; Barbakadze, Ludmila

2015-05-01

The prevalence of polycystic ovarian syndrome (PCOS) particularly is increased in adolescents. Very few longitudinal follow-up for assessment of ovarian reserve in women of late reproductive age with previously confirmed PCOS have been conducted, especially after its diagnosis and treatment in adolescence. The aim of the present study was to compare of the ovarian reserve of the women of late reproductive age by the method of treatment of PCOS in adolescence. This cross sectional study in an unselected population was conducted from January to June 2014. A total of 123 women of late reproductive age were included. They had been diagnosed with PCOS between 1984 and 1990 when they were 13-18 yr. From these, first group of the study was consisted of 67 participants who underwent conservative treatment with antiandrogens and combined oral contraceptives and second group of the study was consisted of 56 participants after surgery (34-bilateral ovarian drilling and 22- ovarian wedge resection). At the time of investigation patients were 35-45 yr. The participants were collected via analysis of histories at primary diagnosis of PCOS in adolescence and at the time of the investigation analyses of reproductive hormones were conducted. Data were compared between the groups. After conservative treatment PCOS women had higher levels of anti- mullerian hormone and lower follicle-stimulating hormone levels (p=0.02 and p=0.04, respectively). The number of antral follicles and mean ovarian volume were significantly greater also, than in women who underwent surgical treatment (p=0.03 and p=0.04, respectively). Our data suggest that PCOS patients who underwent conservative treatment have the better ovarian reserve than women who underwent surgical treatment of PCOS in adolescence.

Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking.

PubMed

Luque-Ramírez, Manuel; Mendieta-Azcona, Covandonga; del Rey Sánchez, José M; Matíes, Milagro; Escobar-Morreale, Héctor F

2009-03-01

To study the blood clotting tests and endothelial function of polycystic ovary syndrome (PCOS) patients and non-hyperandrogenic women, and their changes during PCOS treatment, as a function of the presence of obesity and smoking. Case-control study followed by a randomized clinical trial. Blood clotting and endothelial function were analyzed in 40 PCOS patients and 20 non-hyperandrogenic women. Thirty-four PCOS women were randomized to an oral contraceptive containing 35 microg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35)Diario) or metformin (850 mg twice daily), monitoring the changes on these parameters during 24 weeks of treatment. The influence of obesity and smoking was also analyzed. Blood clotting and endothelial function tests were similar among PCOS patients and controls with the exception of a higher platelet count in the former. Obesity increased circulating fibrinogen levels, prothrombin activity and platelet counts, and reduced prothrombin and activated partial thromboplastin times. Smoking increased fibrinogen levels, platelet counts, and prothrombin activity, and reduced prothrombin time, in relation to the larger waist circumference of smokers. Irrespective of the treatment received, PCOS patients showed a decrease in prothrombin time and an increase in prothrombin activity, with a parallel increase in homocysteine levels in metformin users. The activated partial thromboplastin time decreased markedly in the patients treated with Diane(35)Diario. Finally, flow-mediated dilation improved in non-smokers irrespective of the drug received, but worsened in smokers. Oral contraceptives and metformin may exert deleterious effects on blood clotting tests of PCOS women, yet the effects of metformin appear to be milder. Because smoking potentiates some of these effects and deteriorates endothelial function, smoking cessation should be promoted in PCOS patients.

Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome.

PubMed

Pasquali, R; Gambineri, A; Biscotti, D; Vicennati, V; Gagliardi, L; Colitta, D; Fiorini, S; Cognigni, G E; Filicori, M; Morselli-Labate, A M

2000-08-01

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women [body mass index (BMI) > 28 kg/m2] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1,200-1,400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo). The treatment was

Ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women with polycystic ovary syndrome.

PubMed

Zueff, L F N; Martins, W P; Vieira, C S; Ferriani, R A

2012-03-01

To evaluate whether the presence of polycystic ovary syndrome (PCOS) alters multiple ultrasonographic and laboratory markers of metabolic and cardiovascular disease risk in obese women without any other health condition that could interfere with combined oral contraceptive (COC) eligibility criteria. This was a case-control study evaluating 90 obese women (body mass index (BMI) ≥ 30.0 kg/m(2) and < 40 kg/m(2)) aged between 18 and 40 years without any other health condition that could interfere with COC eligibility criteria, of whom 45 had PCOS and 45 were age-matched controls. BMI, waist and hip circumference, arterial blood pressure, fasting insulin and glucose, quantitative insulin sensitivity check index (QUICKI), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, testosterone, sex hormone-binding globulin, free androgen index (FAI), carotid stiffness index, intima media thickness, flow-mediated dilatation (FMD) of the brachial artery and non-alcoholic fatty liver disease (NAFLD) were assessed. In women with PCOS, we observed a higher frequency of NAFLD (73.3 vs. 46.7%, P < 0.01) and higher FAI (10.4 vs. 6.8%, P < 0.01). We also observed a trend towards increased insulin levels (10.06 ± 6.66 vs. 7.45 ± 5.88 µIU/mL, P = 0.05), decreased QUICKI (0.36 ± 0.06 vs. 0.39 ± 0.07, P = 0.05) and decreased FMD (7.00 ± 3.87 vs. 8.41 ± 3.79%, P = 0.08). No other significant difference was observed. NAFLD is frequent in obese women without any other health condition that could interfere with COC eligibility criteria, especially in those with PCOS. This should be considered when choosing the best contraceptive option. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Hepatic manifestations of women with polycystic ovary syndrome.

PubMed

Chen, Mei-Jou; Ho, Hong-Nerng

2016-11-01

Women with polycystic ovary syndrome (PCOS) have a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) than the general population. The link between NAFLD/NASH and PCOS is not just a coincidence. Indeed, both of these disorders comprise common risk factors, including central obesity, insulin resistance, chronic low-grade inflammation, and hyperandrogenemia. The characteristics of hyperandrogenemia in women with PCOS include elevated total and free testosterone levels and low sex hormone-binding globulin levels and are reported to be associated with NAFLD and elevated liver enzymes; however, not all elevated androgen levels in women with PCOS have the same adverse effects on the liver. With the exception of weight loss and encouraging exercise in obese women, few evidence-based effective treatments target NAFLD/NASH in women with PCOS. Selective antiandrogens and insulin sensitizers might be beneficial in treating NAFLD/NASH in women with PCOS, but further elucidation is needed. Copyright © 2016. Published by Elsevier Ltd.

Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.

PubMed

Jensterle, Mojca; Kravos, Nika Aleksandra; Goričar, Katja; Janez, Andrej

2017-01-31

Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1.2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. Thirty obese women with PCOS (aged 33.1 ± 6.1 years, BMI 38.3 ± 5.4 kg/m 2 ) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1.2 mg QD (N = 15) or liraglutide 3 mg (LIRA3) QD alone (N = 15) for 12 weeks. The primary outcome was change in anthropometric measures of obesity. Both treatments led to significant weight loss (-3.6 ± 2.5 kg, p = 0.002 in COMBO vs -6.3 ± 3.7 kg, p = 0.001 in LIRA3). BMI and waist circumference reduction in LIRA3 was greater than in COMBO (-2.2 ± 1.3 vs -1.3 ± 0.9 kg/m 2 , p = 0.05 and -4.2 ± 3.4 vs -2.2 ± 6.2 cm, p = 0.014, respectively). Both interventions resulted in a significant decrease of post-OGTT glucose levels. COMBO significantly reduced total testosterone and was associated with less nausea. Short-term interventions with COMBO and LIRA3 both led to significant improvement of measures of obesity in obese PCOS, LIRA3 being superior to COMBO. However, COMBO further improved androgen profile beyond weight reduction and was associated with better tolerability. The study was retrospectively registered with ClinicalTrials.gov ( NCT02909933 ) on 16 th of September 2016.

Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?

PubMed

Abu Hashim, Hatem

2016-01-01

The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades. In this review, randomized-controlled trials (RCT) and meta-analyses of RCT comparing metformin are critically appraised and summarized. PubMed and CENTRAL databases were consulted. Evidence is insufficient to favour the use of metformin or metformin plus clomiphene citrate instead of clomiphene citrate for ovulation induction in women with newly diagnosed PCOS. Evidence is also insufficient to recommend metformin as a primary treatment for non-obese women with PCOS. Metformin plus clomiphene citrate should be considered as an effective option in clomiphene citrate-resistant PCOS. In women with PCOS undergoing gonadotrophin ovulation induction, metformin significantly increased pregnancy and live birth rates (P < 0.0001 and P = 0.020, respectively) with reduced risk of cancelled cycles. A beneficial effect of metformin co-treatment in increasing clinical pregnancy rates and reducing the risk of OHSS in PCOS patients undergoing assisted reproduction techniques has been shown. No evidence was found of reduced risk of spontaneous abortion or increased risk of major anomalies in women with PCOS taking metformin during the first trimester. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS).

PubMed

Giallauria, Francesco; Palomba, Stefano; Maresca, Luigi; Vuolo, Laura; Tafuri, Domenico; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo; Francesco, Orio

2008-11-01

Polycystic ovary syndrome (PCOS) is a common female reproductive-age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin-resistance and low-grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin-sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Prospective baseline uncontrolled clinical study. One-hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One-hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS-T (trained) group underwent 3-month ET program, whereas PCOS-UnT (untrained) group did not. At baseline and at 3-month follow-up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C-reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. PCOS-T showed a significant (P < 0.05) improvement in maximal oxygen consumption (VO(2max)) and in post-exercise HRR, and a significant (P < 0.001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS-UnT. Multiple linear regression analysis showed that 3-month HRR is linearly related to the inclusion in training group (beta = 0.316, P < 0.001), VO(2max) (beta = 0.151, P = 0.032) and the ratio between glucose and insulin area under curve (AUC) (beta = 0.207, P = 0.003), and inversely related to body mass index (beta = -0.146, P = 0.046), insulin AUC (beta = -0.152, P = 0.032), CRP (beta = -0.165, P < 0.021), and WBCs count (beta = -0.175, P = 0.039). Exercise training improves autonomic function and inflammatory pattern in PCOS women.

Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

PubMed

Koiou, Ekaterini; Tziomalos, Konstantinos; Katsikis, Ilias; Kandaraki, Eleni A; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Vosnakis, Christos; Panidis, Dimitrios

2012-01-01

Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m(2)) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

Cardiopulmonary functional capacity and the role of exercise in improving maximal oxygen consumption in women with PCOS.

PubMed

Lenarcik, Agnieszka; Bidzińska-Speichert, Bozena

2010-01-01

Polycystic ovary syndrome (PCOS) is one of the most common reproductive disorder in premenopausal women and is frequently accompanied by the presence of cardiovascular risk factors. It has also been recognized that PCOS women are characterized by cardiopulmonary impairment. Reduced cardiopulmonary functional capacity and the autonomic dysfunction associated with abnormal heart rate recovery might be responsible for the increased cardiovascular risk in patients with PCOS. Exercise training has beneficial effects on cardiopulmonary functional capacity and reduces the risk of cardiovascular disease in PCOS women.

The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome.

PubMed

Bik, Wojciech; Baranowska-Bik, Agnieszka; Wolinska-Witort, Ewa; Chmielowska, Magdalena; Martynska, Lidia; Baranowska, Boguslawa

2007-06-01

Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, obesity, dyslipidemia and hypertension. Adiponectin, an adipocyte-specific protein with important roles in glucose and lipid homeostasis, possesses antidiabetic and insulin-sensitizing properties. Ghrelin, a protein ligand for the growth hormone secretagog receptor, has been shown to stimulate food intake and to influence energy balance, insulin signaling and glucose metabolism. We aimed to evaluate the relationships between metabolic alterations and adiponectin and ghrelin levels in lean PCOS women, compared with lean and obese women. The study was carried out on 20 non-obese PCOS women aged 20 - 48 years and age-matched groups of 45 healthy lean and 37 obese women. Hormonal and biochemical parameters, adiponectin and ghrelin concentrations and anthropometric data were determined. In PCOS subjects, we found increased homeostasis model assessment - insulin resistance index (HOMA-IR) with non-significant differences in adiponectin and ghrelin concentrations compared with healthy women, although the PCOS group showed a tendency to lower adiponectin levels. However, ghrelin levels in PCOS women were significantly higher than in obese women. Moreover, we observed a negative correlation between adiponectin and testosterone, cholesterol, triglycerides, glucose and diastolic blood pressure in PCOS. In conclusion, it can be suggested that higher values of HOMA-IR with lower adiponectin levels may indicate future development of metabolic syndrome or other metabolic disturbances in lean PCOS women.

Androgen excess and metabolic disorders in women with PCOS: beyond the body mass index.

PubMed

Condorelli, R A; Calogero, A E; Di Mauro, M; Mongioi', L M; Cannarella, R; Rosta, G; La Vignera, S

2018-04-01

Insulin resistance is a common feature among women with polycystic ovary syndrome (PCOS), especially in those patients with hyperandrogenism and chronic anovulation. PCOS women are at risk for developing metabolic syndrome, impaired glucose tolerance and type II diabetes mellitus (DM II). The aim of this review is to explore the existing knowledge of the interplay between androgen excess, pancreatic β-cell function, non-alcoholic fatty liver disease (NAFLD), intra-abdominal and subcutaneous (SC) abdominal adipocytes in PCOS, providing a better comprehension of the molecular mechanisms of diabetologic interest. A comprehensive MEDLINE ® search was performed using relevant key terms for PCOS and DM II. Insulin-induced hyperandrogenism could impair pancreatic β-cell function, the SC abdominal adipocytes' lipid storage capacity, leading to intra-abdominal adipocyte hypertrophy and lipotoxicity, which in turn promotes insulin resistance, and could enhance NAFLD. Fetal hyperandrogenism exposure prompts to metabolic disorders. Treatment with flutamide showed to partially reverse insulin resistance. Metabolic impairment seems not to be dependent only on the total fat mass content and body weight in women with PCOS and might be ascribed to the androgen excess.

Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.

PubMed

Gambineri, Alessandra; Patton, Laura; De Iasio, Rosaria; Cantelli, Barbara; Cognini, Graciela Estela; Filicori, Marco; Barreca, Antonina; Diamanti-Kandarakis, Evanthia; Pagotto, Uberto; Pasquali, Renato

2005-07-01

Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

Anthropometric, clinical, and metabolic comparisons of the four Rotterdam PCOS phenotypes: A prospective study of PCOS women.

PubMed

Kar, Sujata

2013-07-01

1. To study the distribution of various Rotterdam classified phenotypes of polycystic ovarian syndrome (PCOS) women, in our population. 2. To compare the four phenotypes with respect to anthropometric, clinical, and metabolic parameters. 3. To report the prevalence of insulin resistance (IR) and metabolic syndrome in these women. Private practice, Prospective cross-sectional comparative study. Women attending gynecology outpatient with the primary complains of irregular menses and/or infertility were evaluated. Each of them underwent detailed clinical examination, transvaginal sonography, and biochemical and hormonal assays. Four hundred and ten women with a clinical diagnosis of PCOS based on Rotterdam criteria were included in the study. The four phenotypes were 1) PCO complete, that is oligo/anovulation (O) + polycystic ovaries (P) + hyperandrogenism (H) 2) P + O, 3) P + H, and 4) O + H. All women were also evaluated for metabolic syndrome (American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), modified Adult Treatment Panel (ATP) III 2005 guidelines) and IR (homeostatic model assessment-IR (HOMA-IR)). Statistical Package for Social Sciences (SPSS) version 18. Largest group was PCOS complete (65.6%) followed by P + O (22.2%); H + O (11.2%); and P + H (0.9%). Overall prevalence of metabolic syndrome was 35.07%. Hyperandrogenic phenotyptes; H + O (50%) and P + H + O (37.04%), had significantly higher prevalence of metabolic syndrome than normoandrogenic P + O phenotype (10%) (P ≤ 0.001). Body mass index (BMI) ≥ 25 (P = 0.0004; odds ratio (OR) = 3.07 (1.6574-5.7108, 95% CI)), waist circumference (WC) ≥ 80 cm (P = 0.001; OR = 3.68 (1.6807-8.0737, 95% CI)) and family history of diabetes (P = 0.019; OR 1.82 (1.1008-3.0194, 95% CI)), were strongly associated with the presence of metabolic syndrome. The overall prevalence of IR in PCOS women was 30.44% (HOMA-IR cutoff ≥ 3.8) and 34.94% (HOMA-IR cutoff ≥ 3.5). The prevalence of

No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

PubMed

Marioli, Dimitra J; Koika, Vasiliki; Adonakis, George L; Saltamavros, Alexandros D; Karela, Anastasia; Armeni, Anastasia K; Tsapanos, Vasilios S; Decavalas, George O; Georgopoulos, Neoklis A

2010-06-01

The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

Dyslipidemia in women with polycystic ovary syndrome.

PubMed

Kim, Jin Ju; Choi, Young Min

2013-05-01

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk.

PubMed

Gourgari, E; Lodish, M; Shamburek, R; Keil, M; Wesley, R; Walter, M; Sampson, M; Bernstein, S; Khurana, D; Lyssikatos, C; Ten, S; Dobs, A; Remaley, A T; Stratakis, C A

2015-11-01

Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. This was a cross-sectional case control study. The study was conducted at a clinical research center. Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Blood samples and anthropometric measures were obtained. LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T. Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.

Polycystic Ovary Syndrome (PCOS)

MedlinePlus

... About Share Facebook Twitter Pinterest Email Print About Polycystic Ovary Syndrome (PCOS) PCOS is a set of symptoms related to ... women and girls of reproductive age. What is PCOS? PCOS is a set of symptoms related to ...

Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS.

PubMed

Irani, Mohamad; Minkoff, Howard; Seifer, David B; Merhi, Zaher

2014-05-01

Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis. The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS. DESIGN, SETTINGS, PARTICIPANTS, AND INTERVENTION: Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group. Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured. In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = -0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P < .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01). In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

PubMed

Diamanti-Kandarakis, Evanthia; Katsikis, Ilias; Piperi, Christina; Kandaraki, Eleni; Piouka, Athanasia; Papavassiliou, Athanasios G; Panidis, Dimitrios

2008-10-01

Nonenzymatic advanced glycation and oxidation end-products, advanced glycation end-products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress. Insulin resistant (IR) polycystic ovary syndrome (PCOS) women, have elevated serum AGEs, increased receptor (RAGE) expression, and increased deposition with differential localization in the polycystic ovarian tissue (theca and granulosa) compared to normal. To determine whether the raised AGE levels in noninsulin resistant women with PCOS is a distinct finding compared with those presenting the isolated components of the syndrome and among PCOS subphenotypes. Noninsulin resistant women were selected in order to show that serum AGEs are elevated in PCOS independently of the presence of IR. Clinical trial. One hundred and ninety-three age- and BMI-matched young lean noninsulin resistant women were studied. Among them, 100 women were diagnosed with PCOS according to Rotterdam criteria, and divided to subphenotypes (hyperandrogenaemia with or without PCO morphology and with or without anovulation). Sixty-eight women with the isolated components of the PCOS phenotype were also studied along with 25 healthy women. Serum AGE levels, metabolic, hormonal profiles and intravaginal ultrasound were determined in all subjects. The studied population did not differ in BMI, fasting insulin concentration, waist : hip and glucose : insulin ratios. PCOS women exhibited statistically higher AGEs levels (7.96 +/- 1.87 U/ml, P < 0.001) compared with those with isolated hyperandrogenaemia (5.61 +/- 0.61 U/ml), anovulation (5.53 +/- 1.06 U/ml), US-PCO morphology (5.26 +/- 0.25 U/ml) and controls (5.86 +/- 0.89 U/ml). In PCOS, serum AGEs are distinctly elevated compared with women having the isolated characteristics of the syndrome. No difference was observed between PCOS subphenotypes. As chronic inflammation and increased oxidant stress have been

PCOS women show significantly higher homocysteine level, independent to glucose and E2 level

PubMed Central

Eskandari, Zahra; Sadrkhanlou, Rajab-Ali; Nejati, Vahid; Tizro, Gholamreza

2016-01-01

Background: It is reasonable to think that some biochemical characteristics of follicular fluid (FF) surrounding the oocyte may play a critical role in determining the quality of oocyte and the subsequent potential needed to achieve fertilization and embryo development. Objective: This study was carried out to evaluate the levels of FF homocysteine (Hcy) in IVF candidate polycystic ovary syndrome (PCOS) women and any relationships with FF glucose and estradiol (E2) levels. Materials and Methods: In this case control study which was performed in Dr. Tizro Day Care and IVF Center 70 infertile patients were enrolled in two groups: comprising 35 PCOS and 35 non PCOS women. Long protocol was performed for all patients. FF Hcy, glucose and E2 levels were analyzed at the time of oocyte retrieval. Results: It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (p<0.01). Observations demonstrated that in PCOS group, the Hcy level increased independent to E2, glucose levels, BMI and age, while the PCOS group showed significantly higher BMI compared with non-PCOS group (p=0.03). However, no significant differences were revealed between groups for FF glucose and E2 levels. Conclusion: Present data showed that although FF glucose and E2 levels were constant in PCOS and non PCOS patients, but the FF Hcy levels in PCOS were significantly increased (p=0.01). PMID:27679823

Unaltered timing of embryo development in women with polycystic ovarian syndrome (PCOS): a time-lapse study.

PubMed

Sundvall, Linda; Kirkegaard, Kirstine; Ingerslev, Hans Jakob; Knudsen, Ulla Breth

2015-07-01

Polycystic ovarian syndrome (PCOS) is a common cause of female infertility. Factors other than anovulation, such as low embryo quality have been suggested to contribute to the infertility in these women. This 2-year retrospective study used timelapse technology to investigate the PCOS-influence on timing of development in the pre-implantation embryo (primary endpoint). The secondary outcome measure was live birth rates after elective single-embryo transfer. In total, 313 embryos from 43 PCOS women, and 1075 embryos from 174 non-PCOS women undergoing assisted reproduction were included. All embryos were monitored until day 6. Differences in embryo kinetics were tested in a covariance regression model to account for potential confounding variables: female age, BMI, fertilization method and male infertility. Time to initiate compaction and reach the morula stage as well as the duration of the 4th cleavage division was significantly shorter in PCOS embryos compared with non-PCOS embryos. No other kinetic differences were found at any time-points annotated. The proportion of multi-nucleated cells at the 2-cell stage was significantly higher in PCOS embryos compared with non-PCOS embryos. The live birth rates were comparable between the two groups. The findings suggest that the causative factor for subfertility in PCOS is not related to timing of development in the pre-implantation embryo.

Referral Bias in Defining the Phenotype and Prevalence of Obesity in Polycystic Ovary Syndrome

PubMed Central

Ezeh, Uche; Yildiz, Bulent O.

2013-01-01

Background: The described phenotype of the polycystic ovary syndrome (PCOS) has been primarily based on findings in a referred (self or otherwise) population. It is possible that the phenotype of PCOS would be different if the disorder were to be detected and studied in its natural (unbiased) state. Objective: Our objective was to compare the phenotype of PCOS detected in an unselected population with that identified in a referral population. Participants: Participants included 292 PCOS patients identified at a tertiary care outpatient facility (referral PCOS) and 64 PCOS women (unselected PCOS) identified through the screening of a population of 668 seeking a pre-employment physical. Among the women undergoing a pre-employment physical, 563 did not demonstrate features of the disorder (unselected controls). All PCOS subjects met the National Institutes of Health 1990 criteria for the disorder. Main Outcome Measures: We estimated prevalence of obesity and severity of disease burden. Results: Referral PCOS subjects had greater mean body mass index and hirsutism score and higher degrees of hyperandrogenemia, were more likely to be non-Hispanic White (83.90%), and demonstrated a more severe PCOS subphenotype than unselected PCOS or unselected controls. The prevalence of obesity and severe obesity in referral PCOS was 2.3 and 2.5 times greater than estimates of the same in unselected PCOS and 2.2 and 3.8 times greater than estimates in unselected controls, respectively. Alternatively, unselected PCOS subjects had a prevalence of obesity and severe obesity and a mean body mass index similar to those of the general population from which they were derived. Conclusion: The phenotype of PCOS, including the racial/ethnic mix, severity of presentation, and rate of obesity, is affected significantly by whether the PCOS subject arises from a referral population or through unselected screening, likely reflecting the degree of patient concern and awareness and access to

Studies on the quality nutrition in women with polycystic ovary syndrome (PCOS)

PubMed

Szczuko, Małgorzata; Sankowska, Patrycja; Zapałowska-Chwyć, Marta; Wysokiński, Paweł

Polycystic ovary syndrome (PCOS) manifests itself with various symptoms, therefore it interests representatives of many medical specializations: general practitioners, gynecologists, endocrinologists, dermatologists, cardiologists and those who deal with metabolic disorders, such as dieticians. The aim of this study was perform the qualitative assessment of components of diets of women with PCOS as one of the major factor contributing to the disease. The study was performed on 54 women of childbearing age with PCOS diagnosed according to on the Rotterdam criteria. Qualitative assessment of the diets on the basis of 216 menus was performed based on the analysis of 3-day food diaries and food records taken from the last 24-hour dietary interview. Diets quality assessment was made using three types of point tests: Szewczyński’s Diets’ classification (SDC), Bielińska’s Test with Kulesza’s modification (BTK), Healthy Diet Indicator (HDI). Average waist-hip ratio (WHR) and body mass index (BMI) was above the standard 0.91± 0.08 and 29.16 ± 5.8 kg/m2. Qualitative analysis performed with point tests SDC, BT-K and HDI revealed that the majority of the diets were composed inappropriately, containing many mistakes. Statistically significant correlations (Pearson’s) were determined between HDI test and the body weight and BMI. When analyzing the type of the meals also the correlations (Spearman’s) between BMI and BMI category in BT-K test. Mistakes in diets of women with PCOS are the cause of metabolic disorders related to improper function of ovaries. Native test BT-K seems to be a better method then test SDC and probably HDI of assessing diet in women with PCOS from Poland.

Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome.

PubMed

Christian, Rose C; Dumesic, Daniel A; Behrenbeck, Thomas; Oberg, Ann L; Sheedy, Patrick F; Fitzpatrick, Lorraine A

2003-06-01

Polycystic ovary syndrome (PCOS), a common endocrine disorder of reproductive-aged women, is associated with multiple risk factors for coronary heart disease (CHD), such as diabetes mellitus, dyslipidemia, visceral obesity, and hypertension. However, premature coronary atherosclerosis has not been demonstrated in PCOS women. Electron beam computed tomography (EBCT) noninvasively measures coronary artery calcium (CAC), a marker for coronary atherosclerosis. We measured CAC by EBCT in 30- to 45-yr-old premenopausal PCOS women and compared the results to CAC in 1) recruited normal ovulatory volunteers matched for age and weight to the PCOS cohort, and 2) community-dwelling women of similar age in an extant coronary calcium database. Healthy, community-dwelling, ovulatory controls (n = 71) were matched by age and body mass index (BMI) to PCOS women (n = 36). Women with diabetes or known CHD were excluded. Subjects underwent EBCT scanning, oral glucose tolerance testing, and CHD risk factor assessment. PCOS women had significantly higher levels of serum total and low density lipoprotein cholesterol and testosterone levels than matched controls. PCOS and control women were obese and had a greater mean BMI than community-dwelling women (33 kg/m(2) for PCOS vs. 31 kg/m(2) for control; P < 0.001). CAC was more prevalent in PCOS women (39%) than in matched controls (21%; odds ratio, 2.4; P = 0.05) or community-dwelling women (9.9%; odds ratio, 5.9; P < 0.001). BMI, waist circumference, and total and low density lipoprotein cholesterol levels predicted CAC prevalence after adjustment for BMI. CAC is more prevalent in PCOS women than in obese or nonobese women of similar age. PCOS women are at increased risk for atherosclerosis and should be targeted for primary prevention of CHD.

Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits

PubMed Central

Abbott, D.H.; Levine, J.E.; Dumesic, D.A.

2017-01-01

Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset. PMID:27426126

Translational Insight Into Polycystic Ovary Syndrome (PCOS) From Female Monkeys with PCOS-like Traits.

PubMed

Abbott, David H; Levine, Jon E; Dumesic, Daniel A

2016-01-01

Genetics-based studies of women with polycystic ovary syndrome (PCOS) implicate >20 PCOS risk genes that collectively account for <10% of PCOS. Clinicians now consider that either rare alleles or non-genetic, potentially epigenetic, developmental origins may contribute key pathogenic components to >90% of PCOS cases. Animal models convincingly demonstrate excess fetal testosterone exposure in females as a reliable, epigenetic, developmental origin for PCOS-like traits. In particular, nonhuman primates (NHPs) provide the most faithful emulation of PCOS-like pathophysiology, likely because of close similarities to humans in genomic, developmental, reproductive and metabolic characteristics, as well as aging. Recent appreciation of potential molecular mechanisms contributing to enhanced LH action in both PCOS women (GWAS-based) and PCOS-like monkeys (DNA methylation-based) suggest commonality in pathogenic origins. This review examines the translational relevance of NHP studies to PCOS, identifying characteristics of newborn females at risk for PCOS-like traits and potential prepubertal treatment interventions to ameliorate PCOS onset.

Metformin maintains the weight loss and metabolic benefits following rimonabant treatment in obese women with polycystic ovary syndrome (PCOS).

PubMed

Sathyapalan, Thozhukat; Cho, Li Wei; Kilpatrick, Eric S; Coady, Anne-Marie; Atkin, Stephen L

2009-01-01

Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with polycystic ovary syndrome (PCOS) compared to metformin. Studies have shown that significant weight regain occurs following the cessation of rimonabant therapy. This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS. An extension study for 3 months with the addition of metformin to the randomised open labelled parallel study of metformin and rimonabant in 20 patients with PCOS with a body mass index >or= 30 kg/m(2). Patients who were on 3 months of rimonabant were changed over to metformin for 3 months, whereas those on 3 months of metformin were continued on metformin for another 3 months. The primary end-point was a change in weight; secondary end-points were a change in FAI and insulin resistance. The mean weight loss of 6.2 kg associated with 3 months of rimonabant treatment was maintained by 3 months of metformin treatment (mean change +0.2 kg, P = 0.96). Therefore, the percentage reduction in weight remained significantly higher in the rimonabant/metformin group compared to metformin only subjects at 6 months compared to baseline (-6.0 +/- 0.1%vs. -2.8 +/- 0.1%, P = 0.04). The percentage change in testosterone and FAI from baseline to 6 months was also greater in the rimonabant/metformin group. [Testosterone (-45.0 +/- 5.0%vs. -16 +/- 2.0%, P = 0.02); FAI (-53.0 +/- 5.0%vs. -17.0 +/- 12.2%, P = 0.02)]. HOMA-IR continued to fall significantly in the rimonabant/metformin group between 0, 3 and 6 months (4.4 +/- 0.5 vs. 3.4 +/- 0.4 vs. 2.7 +/- 0.3, respectively, P < 0.01) but not at all in the metformin only group (3.4 +/- 0.7 vs. 3.4 +/- 0.8 vs. 3.7 +/- 0.8, respectively, P = 0.80). Total cholesterol and LDL reduced significantly in both groups, but improvements in triglycerides and HDL were limited to the rimonabant

Genetic and environmental origins of obesity relevant to reproduction.

PubMed

Franks, Stephen

2006-05-01

Obesity has a negative impact on reproductive health, particularly in women with polycystic ovarian syndrome (PCOS). Obesity itself is the product of both genetic and environmental influences, although the current 'epidemic' of obesity is largely related to changes in diet and lifestyle. Single gene defects leading to obesity and disordered reproductive function are rare but can are informative about metabolic pathways involved in appetite regulation. There is good evidence that PCOS has an important genetic background, which probably involves the interaction of several genes. The phenotype of PCOS and its impact on reproductive function is profoundly affected by obesity, which, in turn has both genetic and environmental influences. Understanding the genetic basis of PCOS is important but improvements in diet and lifestyle are the best means of improving reproductive function.

Body mass index and gonadotropin hormones (LH & FSH) associate with clinical symptoms among women with polycystic ovary syndrome.

PubMed

Esmaeilzadeh, Seddigheh; Andarieh, Maryam Ghanbari; Ghadimi, Reza; Delavar, Mouloud Agajani

2014-09-28

To evaluate the relevance of body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH ratio with clinical symptoms in polycystic ovary syndrome (PCOS) women. We reviewed the medical records of all women visited in the PCOS Clinic of Babol (Iran) from 2008 to 2012. A retrospective cross-sectional study was conducted on 175 PCOS women; aged 18-38 years diagnosed based on the Rotterdam criteria. Among the PCOs women, the prevalence of oligomenorrhea, acne, and hirsutism were found to be 92.0%, 31.4%, and 78.9%, respectively. Positive finding of polycystic ovaries was observed in 89.1% of PCOS women with by using sonography. A total of 69.2% overweight/obesity patients had polycystic ovary morphology on ultrasound image. Compared with non- overweight/obesity, the adjusted OR of PCOS women for sonographic view of polycystic ovaries was 4.33 (95% CI, 1.42-13.15, p=0.001), Nevertheless, the adjusted odds ratio (OR) showed no significant associations between LH, FSH, and LH/FSH ratio with clinical symptoms in these women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. Therefore, it is suggested that successful weight loss is the most effective method of restoring ovulation, menstruation that should be used as major advice in obese PCOS patients.

The relationship between subclinical cardiovascular disease and lipocalin-2 levels in women with PCOS.

PubMed

Gencer, Meryem; Gazi, Emine; Hacıvelioğlu, Servet; Binnetoğlu, Emine; Barutçu, Ahmet; Türkön, Hakan; Temiz, Ahmet; Altun, Burak; Vural, Ahmet; Cevizci, Sibel; Kumcular, Tuncer; Coşar, Emine

2014-10-01

In this study we aimed to investigate the relationship between lipocalin-2 (LCN2) levels and cardiovascular risk in patients with polycystic ovary syndrome (PCOS). Fifty patients with PCOS and 44 healthy women as controls were enrolled in the study. Laboratory and echocardiographic examinations were performed between the second and fifth days of the menstrual cycle. Serum LCN2 levels were measured with an enzyme-linked immunosorbent assay (ELISA) method. Serum LCN2 levels were significantly lower in PCOS patients (75.8 [51.4-131.2] ng/ml vs. 85.3 [56.7-138.5] ng/ml, p=0.038). Carotid intima-media thickness (CIMT) was increased in patients with PCOS compared to controls (0.61±0.13mm vs. 0.50±0.07mm, p=0.001). Aortic strain was lower in patients with PCOS. Aortic stiffness (β index) was significantly increased and distensibility was decreased in PCOS patients compared to control subjects. Serum LCN2 levels and the presence of PCOS were associated with CIMT in Spearman correlation analysis (p=0.05 and p<0.001) in all participants. There was no statistically significant relationship between LCN2 levels and CIMT in patients with PCOS (p=0.238). In the present study, we found that LCN2 levels were low in women with PCOS. Although our patients with PCOS had elevated cardiac risk, there was no correlation between LCN2 levels and early findings of atherosclerosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges.

PubMed

Jeanes, Yvonne M; Reeves, Sue

2017-06-01

Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.

Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials.

PubMed

Unfer, V; Carlomagno, G; Dante, G; Facchinetti, F

2012-07-01

Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re-establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS.

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

PubMed

Zhu, Qibo; Zhou, Huang; Zhang, Aipin; Gao, Rufei; Yang, Shumin; Zhao, Changhong; Wang, Yue; Hu, Jinbo; Goswami, Richa; Gong, Lilin; Li, Qifu

2016-01-01

Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level. The study was performed in a clinical research center. Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

PubMed

Rashid, Aafia; Bhat, Javaid Ahmad; Ganie, Mohd Ashraf; Wani, Imtiyaz Ahmad; Bhat, Moomin Hussain; Shah, Zaffar Amin; Masoodi, Shariq R; Marwaha, R K

2018-05-07

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

A three-component cognitive behavioural lifestyle program for preconceptional weight-loss in women with polycystic ovary syndrome (PCOS): a protocol for a randomized controlled trial.

PubMed

Jiskoot, G; Benneheij, S H; Beerthuizen, A; de Niet, J E; de Klerk, C; Timman, R; Busschbach, J J; Laven, J S E

2017-03-06

Obesity in women with polycystic ovary syndrome (PCOS) negatively affects all clinical features, and a 5 to 10% weight loss has shown promising results on reproductive, metabolic and psychological level. Incorporating a healthy diet, increasing physical activity and changing dysfunctional thought patterns in women with PCOS are key points in losing weight. The biggest challenge in weight management programs is to achieve a reasonable and sustainable weight loss. The aim of this study is to explore whether Cognitive Behavioural Therapy (CBT) by a mental health professional, working in a multidisciplinary team with a dietician and a physical therapist (a three-component intervention), is more effective for weight loss in the long term, within 12 months. We will also explore whether mobile phone applications are effective in supporting behavioural change and sustainable weight loss. The present study is a longitudinal randomized controlled trial (RCT) to study the effectiveness of a three-component 1-year cognitive-behavioural lifestyle intervention in overweight/obese women with PCOS. A total of 210 participants are randomly assigned to three groups: 1) CBT provided by the multidisciplinary team or; 2) CBT provided by the multidisciplinary team and Short Message Service (SMS) or; 3) usual care: encourage weight loss through publicly available services (control group). The primary aim of the 12-month intervention is to explore whether a three-component 1-year cognitive-behavioural lifestyle intervention is effective to decrease weight, when compared to usual care. Secondary outcomes include: the effect of the intervention on the PCOS phenotype, waist circumference, waist to hip ratio, ovulation rates, total testosterone, SHBG, free androgen index (FAI), AMH, hirsutism, acne, fasting glucose, blood pressure and all psychological parameters. Additionally, we assessed time to pregnancy, ongoing pregnancies, clinical pregnancies, miscarriages and birth weight. All

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in the Treatment of Obese Women with Polycystic Ovary Syndrome.

PubMed

Tzotzas, Themistoklis; Karras, Spyridon N; Katsiki, Niki

2017-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females and is often associated with a number of cardiometabolic disorders such as central obesity, dyslipidaemia, hypertension, insulin resistance, hyperinsulinaemia, glucose intolerance and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a gut hormone secreted after a meal, enhances glucosestimulated insulin secretion and additionally suppresses appetite and gastric motility. Most studies found impaired GLP-1 kinetics in obese individuals, whereas small studies in PCOS reported reduced, normal or even elevated GLP-1 levels. Apart from their efficacy in patients with T2DM, some GLP-1 receptor agonists (GLP-1 RAs) have been successfully tested in terms of both efficiency and safety in obese individuals without diabetes and liraglutide 3 mg once daily has been approved as an antiobesity drug in the USA and the European Union. Recently, some small trials of short duration using GLP-1 RAs as monotherapy or combined with metformin in obese PCOS women showed positive results regarding weight reduction and a decrease in testosterone levels but without significant effects on insulin levels, insulin sensitivity and menstrual patterns. Longer term studies with more patients and higher doses of liraglutide (as this drug is already approved for obese individuals) are required to determine the precise indications of GLP-1 RAs in PCOS and to evaluate safety issues. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lipoprotein Particles in Adolescents and Young Women With PCOS Provide Insights Into Their Cardiovascular Risk

PubMed Central

Lodish, M.; Shamburek, R.; Keil, M.; Wesley, R.; Walter, M.; Sampson, M.; Bernstein, S.; Khurana, D.; Lyssikatos, C.; Ten, S.; Dobs, A.; Remaley, A. T.; Stratakis, C. A.

2015-01-01

Context: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk. Objective: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism. Design: This was a cross-sectional case control study. Setting: The study was conducted at a clinical research center. Participants: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study. Interventions: Blood samples and anthropometric measures were obtained. Main Outcome Measures: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin. Results: Women with PCOS had higher LDL particle number when compared with healthy controls (935 ± 412 vs 735 ± 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 ± 305 vs 178 ± 195, P = .015). The sLDLp correlated with the Matsuda index (r = −0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = −0.46, P = .0004) but not with T. Conclusion: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity

Effect of Dietary Weight Loss on Menstrual Regularity in Obese Young Adult Women with Polycystic Ovary Syndrome.

PubMed

Marzouk, Tayseer M; Sayed Ahmed, Waleed A

2015-12-01

To investigate the effect of dietary weight loss on menstrual regularity in obese adolescent women with polycystic ovary syndrome (PCOS). A randomized controlled trial was held at the Faculty of Nursing, Mansoura University, and the Obesity Clinic of the Rheumatology Department at Mansoura University Hospitals between July 2011 and January 2013. Sixty adolescent women with PCOS, body mass index (BMI) greater than 30, and complaints of menstrual irregularities were included in this study. Enrolled women were divided equally and randomly into 2 groups: intervention and control groups. Women in the intervention group (n = 30) were subject to an intensive dietary educational program with instructions to follow a conventional energy restricted diet, whereas women in the control group were instructed to follow the same healthy diet of the first group without calorie restriction. Menstrual regularity, weight loss, the effect on waist circumference, and hirsutism score. The 2 groups were initially matched in average body weight, BMI, hirsutism score, and waist circumference. Six months later, there were significant decreases in all parameters in the weight reduction group. In addition, more menstrual episodes were recorded in the weight reduction compared with the control group (3.1 ± 1.2 vs. 2.3 ± 1.3; P = .010). Also, BMI, waist circumference, and hirsutism score were all significantly decreased at the end of the study. Dietary weight loss in adolescent women with PCOS resulted in significant improvement in menstrual regularity, BMI, waist circumference, and hirsutism score. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Melatonin Treatment May Be Able to Restore Menstrual Cyclicity in Women With PCOS: A Pilot Study.

PubMed

Tagliaferri, Valeria; Romualdi, Daniela; Scarinci, Elisa; Cicco, Simona De; Florio, Christian Di; Immediata, Valentina; Tropea, Anna; Santarsiero, Carla Mariaflavia; Lanzone, Antonio; Apa, Rosanna

2018-02-01

The objective of the study was to investigate the effects of 6 months of melatonin administration on clinical, endocrine, and metabolic features of women affected by polycystic ovary syndrome (PCOS). This is a prospective cohort study including 40 normal-weight women with PCOS between January and September 2016, enrolled in an academic research environment. Ultrasonographic pelvic examinations, hirsutism score evaluation, hormonal profile assays, oral glucose tolerance test, and lipid profile at baseline and after 6 months of melatonin administration were performed. Melatonin treatment significantly decreased androgens levels (free androgen index: P < .05; testosterone: P < .01; 17 hydroxyprogesterone: P < .01). Follicle-stimulating hormone levels significantly raised ( P < .01), and anti-Mullerian hormone serum levels significantly dropped after 6 months of melatonin treatment ( P < .01). No significant changes occurred in glucoinsulinemic and lipid parameters after treatment except a significant decrease of low-density lipoprotein cholesterol. Almost 95% of participants experienced an amelioration of menstrual cycles. Until now, only few data have been published about the role of melatonin in women with PCOS. This is the first study focused on the effects of exogenous oral melatonin administration on the clinical, endocrine, and metabolic characteristics of patients with PCOS. After 6 months of treatment, melatonin seems to improve menstrual irregularities and biochemical hyperandrogenism in women with PCOS through a direct, insulin-independent effect on the ovary. Based on our results, melatonin could be considered a potential future therapeutic agent for women affected by PCOS.

Exploring factors related to changes in body composition, insulin sensitivity and aerobic capacity in response to a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome

PubMed Central

Harrison, Cheryce L.; Hutchison, Samantha; de Courten, Barbora; Stepto, Nigel K.

2017-01-01

Objective To determine factors associated with differential changes in body fat, insulin resistance and aerobic capacity following a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome (PCOS). Methods 16 overweight and obese women (9 PCOS; 7 without PCOS) completed a supervised progressive 12-week exercise program. Primary outcomes included changes in indicators of insulin sensitivity (including glucose infusion rate relative to fat-free mass [GIR/FFM]), body composition, and aerobic capacity (VO2 peak; 12 participants only). Comparisons were made between women with and without PCOS, and between participants who lost ≥5% (classified as exercise responders) and <5% (non-responders) in body fat (assessed by dual-energy X-ray absorptiometry). Results Training decreased body fat percentage by (mean; 95% CI) -2.3%; -5.3, 0.7% in women with PCOS and by -6.4%; -10.9, -1.9% in women without PCOS (P = 0.08). Ten women (7 PCOS; 3 without PCOS) did not reduce body fat by ≥5%. All participants improved VO2 peak (mean change 27%; 16–39%) but four (2 PCOS; 2 without PCOS) demonstrated decreases in GIR/FFM (mean change for whole cohort: 37%; 3–71%). Android-gynoid fat ratio (0.58; 0.51, 0.66 vs 0.46; 0.40, 0.51; P<0.01) was significantly higher and GIR/FFM (6.69; 3.49, 9.90 vs 11.44; 9.15, 13.72 mg/kg/min; P = 0.01) was significantly lower in non-responders compared with responders at baseline, but non-responders had significant post-training decreases in android-gynoid ratio (-0.02; -0.04, -0.01; P = 0.03), and increases in VO2 peak (7.24; 2.28, 12.21 mL/kg/min; P = 0.01) and GIR/FFM (1.44; 0.27, 2.61 mg/kg/min; P = 0.02). In women with PCOS, pre-training VO2 peak was significantly negatively correlated with change in total body fat (r = -0.75; P = 0.02), and pre-training fasting glucose negatively correlated with changes in VO2 peak (r = -0.76; P = 0.04), but positively correlated with changes in GIR (r = 0.67; P = 0

Polycystic ovary syndrome and metabolic syndrome in Indigenous Australian women.

PubMed

Boyle, J A; Cunningham, J; Norman, R J; Dunbar, T; O'Dea, K

2015-12-01

Polycystic ovary syndrome (PCOS) affects around 15% of Indigenous women who are also a group at high risk of cardiometabolic disease. To explore the impact of PCOS on metabolic syndrome in Indigenous women. A cross-sectional reproductive health questionnaire, biochemical and anthropometric assessments, of 109 Indigenous women (35 with PCOS and 74 without PCOS) aged 15-44 years in and around Darwin between 2003 and 2005. PCOS was defined using the National Institutes of Health criteria, and metabolic syndrome (MetS) using the National Cholesterol Education Programme Adult Treatment Programme III criteria. The outcome was prevalence of MetS by PCOS status; relationship of PCOS with MetS before and after adjustment for markers of obesity and insulin resistance. Women with PCOS had a significantly higher body mass index (BMI) (P = 0.0001) and MetS was more frequent in women with PCOS (51%) than those without PCOS (23%) (P = 0.003). The most frequent components of MetS in both groups were a high density lipoprotein cholesterol ≤1.29 mmol/L (80% PCOS, 55% non-PCOS) and a waist circumference >88 cm (77% PCOS, 41% non-PCOS); these were significantly more frequent in women with PCOS (P = 0.01). In logistic regression models, PCOS was significantly associated with MetS by itself but not after adjustment for BMI or sex hormone binding globulin. While MetS was more common in Indigenous women with PCOS, PCOS was not an independent predictor of MetS. This may be because obesity and insulin resistance are integral parts of PCOS and are the mechanisms through which PCOS exerts metabolic effects. © 2015 Royal Australasian College of Physicians.

Effect of metformin treatment during pregnancy on women with PCOS: a systematic review and meta-analysis.

PubMed

Tan, Xingrong; Li, Shengbing; Chang, Ying; Fang, Chao; Liu, Hua; Zhang, Xingping; Wang, Yi

2016-09-11

Some previous studies have found that continued metformin use is beneficial in the management of polycystic ovary syndrome (PCOS) in pregnant women. A systemic review and meta-analysis were needed to more fully assess the effects of metformin on pregnant PCOS patients. The literature was fully searched using MEDLINE, EMBASE, SCOPUS, and COCHRANE for continued metformin use during pregnancy in women with PCOS. A systematic review and meta-analysis were performed to evaluate the comprehensive effects of continued metformin treatment on pregnancy-related outcomes in these women. Eleven eligible studies out of 127 relevant publications were included in meta-analysis. The rates of early pregnancy loss and preterm delivery were found to be significantly decreased in metformin-treated PCOS women. A non-significant difference was found in fetal abnormality and fetal birth weight between the metformin-treated and the non-treated groups. The incidence of gestational diabetes mellitus (GDM) and hypertension/preeclampsia were not significantly different in the two groups, probably because of inconsistent results in the subgroup analysis. Our results showed that continued use during of metformin, during pregnancy in women with PCOS, had no effect on incidence of fetal abnormalities or fetal birth weight. The effects of metformin on GDM and hypertension/preeclampsia should be determined through high-quality randomized controlled trials.

Bariatric Surgery Improves Hyperandrogenism, Menstrual Irregularities, and Metabolic Dysfunction Among Women with Polycystic Ovary Syndrome (PCOS).

PubMed

Christ, Jacob P; Falcone, Tommaso

2018-03-02

To characterize the impact of bariatric surgery on reproductive and metabolic features common to polycystic ovary syndrome (PCOS) and to assess the relevance of preoperative evaluations in predicting likelihood of benefit from surgery. A retrospective chart review of records from 930 women who had undergone bariatric surgery at the Cleveland Clinic Foundation from 2009 to 2014 was completed. Cases of PCOS were identified from ICD coding and healthy women with pelvic ultrasound evaluations were identified using Healthcare Common Procedure Coding System coding. Pre- and postoperative anthropometric evaluations, menstrual cyclicity, ovarian volume (OV) as well as markers of hyperandrogenism, dyslipidemia, and dysglycemia were evaluated. Forty-four women with PCOS and 65 controls were evaluated. Both PCOS and non-PCOS had significant reductions in body mass index (BMI) and markers of dyslipidemia postoperatively (p < 0.05). PCOS had significant reductions in androgen levels (p < 0.05) and percent meeting criteria for hyperandrogenism and irregular menses (p < 0.05). OV did not significantly decline in either group postoperatively. Among PCOS, independent of preoperative BMI and age, preoperative OV associated with change in hemoglobin A1c (β 95% (confidence interval) 0.202 (0.011-0.393), p = 0.04) and change in triglycerides (6.681 (1.028-12.334), p = 0.03), and preoperative free testosterone associated with change in total cholesterol (3.744 (0.906-6.583), p = 0.02) and change in non-HDL-C (3.125 (0.453-5.796), p = 0.03). Bariatric surgery improves key diagnostic features seen in women with PCOS and ovarian volume, and free testosterone may have utility in predicting likelihood of metabolic benefit from surgery.

Therapeutic approach for metabolic disorders and infertility in women with PCOS.

PubMed

Morgante, G; Massaro, M G; Di Sabatino, A; Cappelli, V; De Leo, V

2018-01-01

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting 5-10% of women of reproductive age. It generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is defined as a multifactorial pathology, determined by the association of many factors: genetic, endocrine and environmental. The first and most effective treatment of PCOS is to change life-style and lose weight. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. For women with severe hirsutism, the addition of antiandrogens to estrogen-progestin therapy has significantly improved the results. In cases of anovulatory infertility, the drug of first choice is clomiphene citrate, followed by low-dose gonadotropins. Recently, insulin-sensitizing drugs have been widely prescribed for PCOS patients. They are particularly effective in reducing insulin resistance and improving ovulatory performance. Besides insulin-sensitizing drugs, natural substances, such as inositol, seems to have good efficacy, similar to metformin with fewer side effects. New substances that could be used include statins and natural statins, such as monakolin, alone or combined with myo-inositol. These substances do not have side effects and greatly reduce the hyperandrogenic component in these patients.

Sympathetic activation and endothelial dysfunction in polycystic ovary syndrome are not explained by either obesity or insulin resistance.

PubMed

Lambert, Elisabeth A; Teede, Helena; Sari, Carolina Ika; Jona, Eveline; Shorakae, Soulmaz; Woodington, Kiri; Hemmes, Robyn; Eikelis, Nina; Straznicky, Nora E; De Courten, Barbora; Dixon, John B; Schlaich, Markus P; Lambert, Gavin W

2015-12-01

Polycystic ovary syndrome (PCOS) is a common endocrine condition underpinned by insulin resistance and associated with increased risk of obesity, type 2 diabetes and adverse cardiovascular risk profile. Previous data suggest autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction in PCOS. However, it is not clear whether these abnormalities are driven by obesity and metabolic disturbance or whether they are independently related to PCOS. We examined multiunit and single-unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis) and endothelial function [ischaemic reactive hyperaemia index (RHI) using the EndoPAT device] in 19 overweight/obese women with PCOS (BMI: 31·3 ± 1·5 kg/m(2), age: 31·3 ± 1·6 years) and compared them with 21 control overweight/obese women (BMI: 33·0 ± 1·4 kg/m(2), age: 28·2 ± 1·6 years) presenting a similar metabolic profile (fasting total, HDL and LDL cholesterol, glucose, triglycerides, insulin sensitivity and blood pressure). Women with PCOS had elevated multiunit muscle SNS activity (41 ± 2 vs 33 ± 3 bursts per 100 heartbeats, P < 0·05). Single-unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes (P < 0·01 for all parameters). Women with PCOS also had impaired endothelial function (RHI: 1·77 ± 0·14 vs 2·18 ± 0·14, P < 0·05). HRV did not differ between the groups. Women with PCOS have increased sympathetic drive and impaired endothelial function independent of obesity and metabolic disturbances. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS. © 2015 John Wiley & Sons Ltd.

Prevalence of metabolic syndrome in relation to body mass index and polycystic ovarian syndrome in Indian women.

PubMed

Sharma, Sangita; Majumdar, Abha

2015-01-01

To study the prevalence of metabolic syndrome (MBS) in Indian women and to see how does it correlate to body mass index (BMI) and polycystic ovarian syndrome (PCOS) in this population. Prospective cross-sectional observational study. Infertility clinic of a tertiary center. Two hundred women, 120 with PCOs and 80 age-matched controls were enrolled. The prevalence of MBS was studied in the women with and without and was co related to BMI by further subgrouping as team (BMI <23 kg/m3) and obese (BMI >23 kg/m2). The sample size was: team controls-40, obese controls-40, team PCOS-80. Each subject underwent a physical examination and laboratory evaluation for the diagnosis of MBS, which was defined according to the guidelines of National Cholesterol Education Program Adult Treatment Pamel (NCEP ATP III) 2005. None. Subjects with and without PCOs were compared with each other for the prevalence of MBS, and similarly team subjects were compared with obese subjects. Receiver operator characteristic (ROC) curves were obtained for both the PCOS and non PCOS population separately, co-relating the prevalence of MBS with BMI. These ROC curves were used to establish the cut off values of BMI, which could best predict the risk of MBS. The prevalence of MBS was significantly higher in the women with PCOS, as compared to age-matched controls. Similarly, when BMI was considered, MBS was more prevalent in overweight subjects than in lean subjects with or without PCOS. In subgroup analysis, the presence of PCOS had a lesser impact on the prevalence of MBS as compared to non-PCOS controls with higher BMI. The relative risk of MBS increased as follows: lean controls-1, lean PCOS-2.66, obese controls-5.33, and obese PCOS-6.5. The most appropriate cut-off level of BMI for predicting the risk of MBS in Indian women without PCOS seems to be 23 kg/m(2), whereas, with PCOS, it was 22.5 kg/m(2). MBS is more prevalent in women with PCOS. However, obesity is an independent and stronger risk

Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis.

PubMed

Misso, Marie L; Costello, Michael F; Garrubba, Marie; Wong, Jennifer; Hart, Roger; Rombauts, Luk; Melder, Angela M; Norman, Robert J; Teede, Helena J

2013-01-01

BACKGROUND Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32 kg/m(2) was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system). METHODS Databases were searched for English language articles until July 2011. women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk). RESULTS The search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the RCTs. CONCLUSIONS Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m(2). However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to

Influence of adrenal hyperandrogenism on the clinical and metabolic phenotype of women with polycystic ovary syndrome.

PubMed

Alpañés, Macarena; Luque-Ramírez, Manuel; Martínez-García, M Ángeles; Fernández-Durán, Elena; Álvarez-Blasco, Francisco; Escobar-Morreale, Héctor Francisco

2015-03-01

To study the impact of adrenal hyperandrogenism (AH; defined as DHEAS concentration >95th percentile of a healthy female control population) on cardiometabolic risk factors associated with polycystic ovary syndrome (PCOS). Cross-sectional study. Academic hospital. Two-hundred ninety-eight consecutive women with PCOS, of whom 120 were obese (body mass index [BMI] ≥30 kg/m(2)) and 178 nonobese (BMI <30 kg/m(2)). None. Comprehensive evaluation of cardiovascular risk factors, including 75-g oral glucose tolerance test, office blood pressure, lipid profile, and low-grade inflammatory markers. Patients with AH (AH-PCOS) had higher insulin circulating levels and lower insulin sensitivity than their counterparts without AH (non-AH-PCOS). Obesity, but not AH, was the main contributor to the presence of glucose tolerance disorders. Both obesity and AH increased the prevalence of prehypertension and hypertension. AH diminished high-density lipoprotein (HDL) levels in nonobese PCOS women in parallel with a decrease in total cholesterol levels, leading to a total to HDL cholesterol ratio similar to that of nonobese non-AH-PCOS patients. Furthermore, AH blunted the deleterious effect of obesity on the total cholesterol/HDL ratio, with the ratio of obese AH-PCOS patients being similar to that of nonobese PCOS patients with or without AH. The presence of AH in women with PCOS is associated with reduced insulin sensitivity and increased blood pressure but may have beneficial impact on the lipid profile. Obesity is the main determinant of the clustering of cardiovascular risk factors in PCOS women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.

PubMed

Rees, E; Coulson, R; Dunstan, F; Evans, W D; Blundell, H L; Luzio, S D; Dunseath, G; Halcox, J P; Fraser, A G; Rees, D A

2014-09-01

Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P < 0.001) and higher testosterone (AD 0.57 nmol/l, P < 0.001) and high molecular weight adiponectin than controls (AD 3.01 µg/ml, P = 0.02), but no significant differences in aPWV (AD -0.13 m/s, P = 0.33), ccIMT (AD -0.01 mm, P = 0.13), or e':a' (AD -0.01, P = 0.86) were observed. After adjustment for age, height and central pulse pressure, e':a' and aPWV were associated with log

Visfatin and retinol-binding protein 4 concentrations in lean, glucose-tolerant women with PCOS.

PubMed

Yildiz, Bulent O; Bozdag, Gurkan; Otegen, Umit; Harmanci, Ayla; Boynukalin, Kubra; Vural, Zehra; Kirazli, Serafettin; Yarali, Hakan

2010-01-01

Since insulin resistance is accepted to be a common feature of polycystic ovary syndrome (PCOS), the exact molecular mechanism(s) involved in glucose and lipid metabolism have been under investigation in the syndrome. Recently, two novel adipokines, namely visfatin and retinol-binding protein 4 (RBP4), have been suggested to play a role in insulin resistance and diabetes. This study sought to determine whether plasma concentrations of visfatin and RBP4 are altered in PCOS by comparing a total of 27 lean, normal glucose-tolerant PCOS patients with 19 age- and body mass index-matched healthy controls. The mean plasma visfatin concentrations were higher in PCOS patients than those in healthy subjects (37.9+/-18.2 versus 19.8+/-17.5, P<0.01), while RBP4 concentrations were similar between the two. Both adipokines were correlated with each other in the whole (r=0.50, P<0.01) and in PCOS (r=0.52, P<0.01) groups but not in controls. The results suggest that lean, glucose-tolerant women with PCOS have increased circulating visfatin and unaltered RBP4 concentrations compared with healthy lean women. In order to clarify overlapping effects and their potential contribution to the pathophysiology of PCOS, further studies are needed. Copyright (c) 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage.

PubMed

Hart, Roger; Doherty, Dorota A

2015-03-01

The polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age. To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS. A population-based retrospective cohort study using data linkage in a statewide hospital morbidity database system. All hospitals within Western Australia. A total of 2566 women with PCOS hospitalized from 1997-2011 and 25 660 randomly selected age-matched women without a PCOS diagnosis derived from the electoral roll. Hospitalizations by ICD-10-M diagnoses from 15 years were compared. Hospitalizations were followed until a median age of 35.8 years (interquartile range, 31.0-39.9). PCOS was associated with more nonobstetric and non-injury-related hospital admissions (median, 5 vs 2; P < .001), a diagnosis of adult-onset diabetes (12.5 vs 3.8%), obesity (16.0 vs 3.7%), hypertensive disorder (3.8 vs 0.7%), ischemic heart disease (0.8 vs 0.2%), cerebrovascular disease (0.6 vs 0.2%), arterial and venous disease (0.5 vs 0.2% and 10.4 vs 5.6%, respectively), asthma (10.6 vs 4.5%), stress/anxiety (14.0 vs 5.9%), depression (9.8 vs 4.3%), licit/illicit drug-related admissions (8.8 vs 4.5%), self-harm (7.2 vs 2.9%), land transport accidents (5.2 vs 3.8%), and mortality (0.7 vs 0.4%) (all P < .001). Women with PCOS had a higher rate of admissions for menorrhagia (14.1 vs 3.6%), treatment of infertility (40.9 vs 4.6%), and miscarriage (11.1 vs 6.1%) and were more likely to require in vitro fertilization (17.2 vs 2.0%). PCOS has profound medical implications for the health of women, and health care resources should be directed accordingly.

Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome.

PubMed

Zwirska-Korczala, K; Sodowski, K; Konturek, S J; Kuka, D; Kukla, M; Brzozowski, T; Cnota, W; Woźniak-Grygiel, E; Jaworek, J; Bułdak, R; Rybus-Kalinowska, B; Fryczowski, M

2008-08-01

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY

Obesity and female fertility: a primary care perspective.

PubMed

Wilkes, Scott; Murdoch, Alison

2009-07-01

Infertility affects approximately one in six couples during their lifetime. Obesity affects approximately half of the general population and is thus a common problem among the fertile population. Obese women have a higher prevalence of infertility compared with their lean counterparts. The majority of women with an ovulatory disorder contributing to their infertility have polycystic ovary syndrome (PCOS) and a significant proportion of women with PCOS are obese. Ovulation disorders and obesity-associated infertility represent a group of infertile couples that are relatively simple to treat. Maternal morbidity, mortality and fetal anomalies are increased with obesity and the success of assisted reproductive technology (ART) treatments is significantly reduced for obese women. Body mass index (BMI) treatment limits for ART throughout the UK vary. The mainstay for treatment is weight loss, which improves both natural fertility and conception rates with ART. The most cost-effective treatment strategy for obese infertile women is weight reduction with a hypo-caloric diet. Assisted reproduction is preferable in women with a BMI of 30 kg/m(2) or less and weight loss strategies should be employed within primary care to achieve that goal prior to referral.

The diagnosis of PCOS in young infertile women according to different diagnostic criteria: the role of serum anti-Müllerian hormone.

PubMed

Casadei, Luisa; Fanisio, Francesca; Sorge, Roberto Pietro; Collamarini, Matteo; Piccolo, Eleonora; Piccione, Emilio

2018-07-01

To diagnose polycystic ovary syndrome (PCOS) in young infertile women using different diagnostic criteria. To define serum anti-Müllerian hormone (AMH) cutoff values for PCOS definition. To investigate the correlation between AMH and body mass index (BMI). Retrospective case-control study. A total of 140 infertile women (age 21-35 years) were enrolled. PCOS was defined according to the National Institutes of Health (NIH) criteria, the Rotterdam consensus criteria and the Androgen Excess and PCOS Society (AE-PCOS) criteria. ROC curve analysis was performed to define AMH thresholds for PCOS definition according to the three different diagnostic criteria. Correlation between AMH and BMI was investigated. The prevalence of PCOS under the NIH criteria, the Rotterdam criteria and the AE-PCOS criteria was 27.1, 40 and 29.3%, respectively. The optimal thresholds of AMH to distinguish NIH PCOS from infertile controls was 5.20 ng/ml (AUC = 0.86, sensitivity 79%, specificity 80%); the best cutoff to detect Rotterdam PCOS was 4.57 ng/ml (AUC = 0.85, sensitivity 78%, specificity 81%); a cutoff of 4.85 ng/ml (AUC = 0.85, sensitivity 80%, specificity 78%) defined PCOS women according to AE-PCOS criteria. The prevalence of the syndrome became 37.1, 44.3 and 39.2% according to the three criteria, respectively, using AMH threshold between 4.57 and 5.20 ng/ml as an alternative to antral follicle count and/or hyperandrogenism. Anti-Müllerian hormone may reconcile the three diagnostic criteria and allow the PCOS diagnosis in women with mild symptoms. No significant correlation was found between AMH and BMI in PCOS women and controls.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Pangaribuan, Bertha; Yusuf, Irawan; Mansyur, Muchtaruddin; Wijaya, Andi

2011-12-01

The role of insulin resistance in polycystic ovary syndrome (PCOS) has been established. However the role of adiponectin and resistin in the relationship between insulin resistance as markers of obesity and PCOS has not been conclusive. This study aims to determine the influence of the serum levels of adiponectin and resistin on PCOS, and assess possible correlations with the hormonal and metabolic parameters of the syndrome and obesity. This study continued a case control study that had finished recruiting 24 subjects of reproductive women with PCOS as a case group, and 24 subjects of normal ovulatory reproductive women without hyperandrogenism as a control group. Further, only 18 subjects of the control group had a body mass index (BMI) <25 kg/m(2) and were included the data analysis, whereas others were excluded. Therefore, these study data were divided into three groups. Twenty-four PCOS patients from the case group were allocated to two groups, A (n = 14) patients had PCOS + BMI ≥25 kg/m(2); B (n = 10) patients had PCOS + BMI <25 kg/m(2). Group C was the control group of 18 reproductive women without PCOS + BMI <25 kg/m(2). Blood samples were collected between day 3 and 5 of a spontaneous menstrual cycle, at 07:00 to 09:00, after overnight fasting. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, sex hormone-binding globulin (SHBG), glucose, insulin, adiponectin and resistin were measured. Serum adiponectin levels were significantly decreased in group A compared with group B and group C. No significant difference existed in adiponectin between group B and group C. Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR) value in group A was found to be significantly higher than group C, but no significant differences were found between group B and group C or between group A and group B. There was no significant difference in serum resistin between all groups

Office blood pressure, ambulatory blood pressure monitoring, and echocardiographic abnormalities in women with polycystic ovary syndrome: role of obesity and androgen excess.

PubMed

Luque-Ramírez, Manuel; Martí, David; Fernández-Durán, Elena; Alpañés, Macarena; Álvarez-Blasco, Francisco; Escobar-Morreale, Héctor F

2014-03-01

Whether or not blood pressure (BP) and heart function of women with polycystic ovary syndrome (PCOS) are altered remains unclear, albeit subtle abnormalities in the regulation of BP observed in these women might suggest a mild masculinization of their cardiovascular system. To study the influence of obesity and androgen excess on BP and echocardiographic profiles of women with the syndrome, we conducted a cross-sectional case-control study comparing office and ambulatory BP monitoring, as well as echocardiographic assessments, in 63 premenopausal women with the classic phenotype, 33 nonhyperandrogenic women with regular menses, and 25 young men. Forty-nine subjects were lean and 72 had weight excess (body mass index ≥25 kg/m(2)). Participants had no previous history of hypertension and were nonsmokers. Men showed the highest BP readings, and the lowest readings were observed in control women, whereas women with PCOS had intermediate values. Undiagnosed hypertension was more common in subjects with weight excess irrespective of sex and hyperandrogenism. Women with PCOS and weight excess showed frequencies of previously undiagnosed hypertension that were similar to those of men with weight excess and higher than those observed in nonhyperandrogenic women. Lastly, male sex, weight excess and hypertension, the latter in men as well as in women with PCOS, increased left ventricular wall thickness. In summary, our results show that patients with classic PCOS and weight excess frequently have undiagnosed BP abnormalities, leading to target organ damage.

A potential determinant role of adiponectin and receptors for the early embryo development in PCOS patients with obesity hinted by quantitative profiling.

PubMed

Zhang, Ning; Hao, Cuifang; Liu, Xiaoyan; Zhang, Shouxin; Zhang, Fengrong; Zhuang, Lili; Zhao, Dongmei

2017-02-01

To identify the quantitative profiling of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) in cumulus cells (CCs) and to evaluate their roles in the early embryo development of polycystic ovary syndrome (PCOS) patients, in part, with obesity. Fifty-five subjects were divided into two groups according to the body mass index. Oocytes were further inseminated and only mature and normal fertilized oocytes (2PN) were included in this research. Real-time PCR and western blot were performed to identify adiponectin and its receptors in CCs. Adiponectin and receptors were ubiquitously expressed in CCs of PCOS and non-PCOS patients. The level of AdipoR2 in CCs from the oocytes yielding blastocyst after 5/6 days in vitro culture was markedly higher than in those from oocytes could not develop to blastocyst stage after Day 6, for non-obese or obese PCOS patients (0.1647 ± 0.0161 versus 0.0783 ± 0.0385, 0.1948 ± 0.0307 versus 0.1057 ± 0.0236, respectively, p < 0.05). In addition, only in patients with PCOS and concurrent obesity the AdipoR1 in CCs was considerably increased in CC-B + compared with CC-B - subgroup (0.5162 ± 0.0371 versus 0.2448 ± 0.0333, p < 0.01). The development of early embryo was associated with the up-regulation of AdipoR1 and AdipoR2 in PCOS patients. Our results suggested that adiponectin could positively modulate embryo development in humans. Further investigations should be carried out to unlock the crucial role that adiponectin plays in embryo development.

Serum chemerin level in women with PCOS and its relation with the risk of spontaneous abortion.

PubMed

Yang, Xuezhou; Quan, Xiaozhen; Lan, Yanli; Wei, Qipeng; Ye, Jinhai; Yin, Xiaofang; Ji, Zhisong; Xing, Hui; Yang, Ying

2018-04-16

Insulin resistance (IR) was recognized as a risk factor for the occurrence of abortion in patients with polycystic ovary syndrome (PCOS). Chemerin was an adipokine which could induce IR and associated with reproductive process closely. However, few studies have inquired the relativity between chemerin and the occurrence of abortion in patients with PCOS. The aim of this study was to evaluate the relationship between serum chemerin and the occurrence of abortion in women with PCOS. We recruited 198 women with PCOS to participate in our study. On the third day of menstrual cycle or a random day in women with amenorrhea, we obtained their venous blood and measured the fasting insulin, fasting plasma glucose, total cholesterol, high density lipoprotein cholesterol, triglyceride, chemerin, and hormones including FSH, E2, P, PRL, LH, and T. Additionally, BMI, HOMA-IR and LH/FSH of each subject were calculated. Finally, 58 of them were included in the study, in which 30 of them had normal pregnancy and the other 28 had an early miscarriage. We compared the biochemical characteristics between the normal pregnancy group and abortion group by independent-samples t test. In our study, those with a normal pregnancy had a lower level of BMI, FINs, HOMA-IR, and chemerin compared to abortion patients (p < .05). After adjusted for BMI, only chemerin was associated with the occurrence of abortion in PCOS patients (p < .05). Serum chemerin level is associated with the occurrence of abortion in patients with PCOS. Thus, serum chemerin may serve as a biomarker to identify pregnant women with PCOS who are at particular risk for later abortion, and who may benefit from prevention strategies.

Cardiovascular disease risk in young Indian women with polycystic ovary syndrome.

PubMed

Guleria, A K; Syal, S K; Kapoor, A; Kumar, S; Tiwari, P; Dabadghao, P

2014-01-01

Polycystic ovary syndrome (PCOS) is associated with significant risk factors for cardiovascular disease (CVD) like insulin resistance, hyperinsulinism, hypertension and dyslipidemia. We studied CVD risk in young women (18-35 years age) with PCOS using carotid intima media thickness (CIMT) and brachial artery flow mediated dilation (FMD) which are markers of subclinical atherosclerosis. Fifty women with PCOS (age: 24.3 ± 4 years; body mass index [BMI]: 24.6 ± 4 kg/m(2)) were compared with 50 age and BMI matched healthy controls (age: 24.6 ± 5 years; BMI: 23.9 ± 4 kg/m(2)). CIMT was significantly higher (0.55 ± 0.09 mm versus 0.40 ± 0.1 mm, p value <0.0001) and FMD was significantly lower (9.39 ± 4.36% versus 13.89 ± 4.77%, p value <0.0001) in cases as compared to controls. These differences in CIMT and FMD remained significant when subgroup were analyzed, obese PCOS versus obese controls and non obese PCOS versus non-obese controls. In stepwise linear regression PCOS was associated with CIMT and FMD independent of age, BMI and blood pressure. Young women with PCOS irrespective of their BMI have evidence for increased CVD risk as shown by increased CIMT and a lower FMD.

Androgens influence microvascular dilation in PCOS through ET-A and ET-B receptors

PubMed Central

Wenner, Megan M.; Taylor, Hugh S.

2013-01-01

Hyperandrogenism and vascular dysfunction often coexist in women with polycystic ovary syndrome (PCOS). We hypothesized that testosterone compromises cutaneous microvascular dilation in women with PCOS via the endothelin-1 ET-B subtype receptor. To control and isolate testosterone's effects on microvascular dilation, we administered a gonadotropin-releasing hormone antagonist (GnRHant) for 11 days in obese, otherwise healthy women [controls, 22.0 (4) yr, 36.0 (3.2) kg/m2] or women with PCOS [23 (4) yr, 35.4 (1.3) kg/m2], adding testosterone (T; 2.5 mg/day) on days 8–11. Using laser Doppler flowmetry and cutaneous microdialysis, we measured changes in skin microcirculatory responsiveness (ΔCVC) to local heating while perfusing ET-A (BQ-123) and ET-B (BQ-788) receptor antagonists under three experimental conditions: baseline (BL; prehormone intervention), GnRHant (day 4 of administration), and T administration. At BL, ET-A receptor inhibition enhanced heat-induced vasodilation in both groups [ΔCVC control 2.03 (0.65), PCOS 2.10 (0.25), AU/mmHg, P < 0.05]; ET-B receptor inhibition reduced vasodilation in controls only [ΔCVC 0.98 (0.39), 1.41 (0.45) AU/mmHg for controls, PCOS] compared with saline [ΔCVC controls 1.27 (0.48), PCOS 1.31 (0.13) AU/mmHg]. GnRHant enhanced vasodilation in PCOS [saline ΔCVC 1.69 (0.23) AU/mmHg vs. BL, P < 0.05] and abolished the ET-A effect in both groups, a response reasserted with T in controls. ET-B receptor inhibition reduced heat-induced vasodilation in both groups during GnRHant and T [ΔCVC, controls: 0.95 (0.21) vs. 0.51 (13); PCOS: 1.27 (0.23) vs. 0.84 (0.27); for GnRHant vs. T, P < 0.05]. These data demonstrate that androgen suppression improves microvascular dilation in PCOS via ET-A and ET-B receptors. PMID:23921139

Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.

PubMed

Panidis, Dimitrios; Farmakiotis, Dimitrios; Rousso, David; Kourtis, Anargyros; Katsikis, Ilias; Krassas, Gerassimos

2008-04-01

To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. Prospective clinical study. Department of obstetrics and gynecology in a major university in Greece. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

Short-term intervention with liraglutide improved eating behavior in obese women with polycystic ovary syndrome.

PubMed

Jensterle, Mojca; Kocjan, Tomaz; Kravos, Nika Aleksandra; Pfeifer, Marija; Janez, Andrej

2015-01-01

Glucagon-like peptide 1 receptor agonists (GLP-1 RA) stimulate satiety leading to reductions in food intake and body weight. The effects of long- acting GLP-1 RA liraglutide on eating behavior of women with PCOS have not been investigated yet. Thirty-six obese women with PCOS (mean ± SD, aged 31.2 ± 7.8 years, with BMI 38.7 ± 0.1 kg/m(2)), pretreated with metformin (1000 mg BID) were switched to liraglutide 1.2 mg QD sc for 12 weeks. Adiposity parameters and eating behavior as assessed by Three-Factor Eating Questionnaire (TFEQ-R18) were examined at baseline and after 12 weeks. Subjects treated with liraglutide lost on average 3.8 ± 0.1 kg (p < 0.001). Significant reductions of waist circumference and visceral adipose tissue (VAT) mass, volume and area were demonstrated from liraglutide induction to the end of the study. TFEQ-R18 scores were significantly different pre- and post-liraglutide intervention. After treatment with liraglutide the uncontrolled eating (UE) score decreased from 36.8 ± 24.5 to 19.6 ± 18.4 (p < 0.001) and emotional eating (EE) score decreased from 49.9 ± 33.3 to 28.5 ± 26.9 (p < 0.001). Scores for cognitive restraint (CR) were not changed. Short-term liraglutide treatment was associated with weight loss and significantly improved eating behavior in obese women with PCOS.

Avoiding OHSS: Controlled Ovarian Low-Dose Stimulation in Women with PCOS.

PubMed

Fischer, D; Reisenbüchler, C; Rösner, S; Haussmann, J; Wimberger, P; Goeckenjan, M

2016-06-01

The polycystic ovary syndrome is a common endocrine disorder which influences outcome and potential risks involved with controlled ovarian stimulation for artificial reproductive techniques (ART). Concrete practical recommendations for the dosage of gonadotropins, the preferred protocol and preventive methods to avoid ovarian hyperstimulation syndrome (OHSS) are lacking. We present retrospective data of 235 individually calculated gonadotropin low-dose stimulations for ART in a single center from 2012 to 2014. Clinical data and outcome parameter of patients diagnosed with PCOS according to Rotterdam criteria (n = 39) were compared with patients without PCOS (n = 196). The starting dose of gonadotropins was individually calculated depending on patients' age, BMI, ovarian reserve, ovarian response in previous cycles, and diagnostic criteria of PCOS. Mean age and duration of infertility did not differ between the groups, whereas mean BMI (p = 0.007) and AMH (p < 0.001) were higher in the PCOS-group. A lower mean FSH-starting and maximum dose was administered to women with PCOS (p < 0.001). The biochemical pregnancy rate of 42.4 % and the clinical pregnancy rate of 32.2 % for PCOS-patients did not differ from those of the control group (42.2 % and 34.4 % respectively). Neither mild, nor moderate or severe manifestation of OHSS occurred significantly more often in patients with PCOS. Our study supports the use of a calculated low-dose FSH-stimulation strategy in ART for patients with PCOS. Further randomized clinical trials should confirm this strategy and lead to define individual risk factors for OHSS, which can be used for recommendation of safer ART-techniques like in vitro maturation.

Prior caloric restriction increases survival of prepubertal obese- and PCOS-prone rats exposed to a challenge of time-limited feeding and physical activity.

PubMed

Diane, Abdoulaye; Vine, Donna F; Heth, C Donald; Russell, James C; Proctor, Spencer D; Pierce, W David

2013-05-01

We hypothesized that a polycystic ovary syndrome (PCOS) background associated with obese-prone genotype, coupled with preconditioning by caloric restriction, would confer a survival benefit in genetically prepubertal obese/PCOS (O/PCOS)-prone rats faced with an unpredictable challenge of food shortage. Female, juvenile JCR:LA-cp rats, O/PCOS- and lean-prone, were exposed to 1.5 h of daily meals and 22.5 h of voluntary wheel-running, a procedure that leads to activity anorexia (AA). One week before the AA challenge (AAC), O/PCOS-prone rats were freely fed (O/PCOS-FF) or pair fed (O/PCOS-FR) to lean-prone, free-feeding animals (Lean-FF). O/PCOS-FR and lean-prone, food-restricted (Lean-FR) groups were matched on relative average caloric intake. Animals were removed from protocol at 75% of initial body weight (starvation criterion) or after 14 days (survival criterion). The AAC induced weight loss in all rats, but there were significant effects of both genotype and feeding history on weight loss (lean-prone rats exhibited a higher rate of weight loss than O/PCOS-prone; P < 0.001), and rats with prior caloric restriction retained more weight than those free fed previously (90.68 ± 0.59% vs. 85.47 ± 0.46%; P < 0.001). The daily rate of running was higher in lean-prone rats compared with O/PCOS-prone. This difference in running rate correlated with differences in mean days of survival. All O/PCOS-FR rats survived at day 14. O/PCOS-FF rats survived longer (10.00 ± 0.97 days) than Lean-FR (6.17 ± 1.58 days) and Lean-FF (4.33 ± 0.42 days) rats (P < 0.05). Thus preconditioning by caloric restriction induces a substantial survival advantage, beyond genotype alone, in prepubertal O/PCOS-prone rats.

Effect of maternal PCOS and PCOS-like phenotype on the offspring’s health

PubMed Central

Puttabyatappa, Muraly; Cardoso, Rodolfo C.; Padmanabhan, Vasantha

2015-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities affecting women of reproductive age. While the exact origin of PCOS is unknown, observations from clinical and animal studies suggest that maternal hyperandrogenism may be a contributing factor. Because women with PCOS manifest hyperandrogenism during pregnancy, changes in the gestational endocrine milieu may play a role in the vertical transmission of this syndrome. This review discusses the potential developmental origins of PCOS, the impact of maternal PCOS on the offspring’s health and contributions of the postnatal environment, capitalizing on findings from animal models that exhibit a PCOS-like phenotype. In addition, this review highlights the scarcity of data at early gestational stages in humans and the importance of animal experimentation to better understand the cellular and molecular mechanisms involved in the programming of adult diseases, therefore, helping identify therapeutic targets for preventive and treatment strategies. PMID:26639019

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome

PubMed Central

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have. PMID:27570464

Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome.

PubMed

Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

2016-01-01

Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have.

The effects of a low-calorie diet or an isocaloric diet combined with metformin on sex hormones In obese women of child-bearing age.

PubMed

Swora-Cwynar, Ewelina; Kujawska-Łuczak, Magdalena; Suliburska, Joanna; Reguła, Julita; Kargulewicz, Angelika; Kręgielska-Narożna, Matylda; Marcinkowska, Emilia; Kanikowska, Alina; Bielas, Marzena; Grzymisławski, Marian; Bogdański, Paweł

2016-01-01

The influence of weight loss treatment on sex hormones profile has been studied mainly in women with polycystic ovary syndrome (PCOS), but in obese premenopausal women without PCOS it still remains unclear. The aim of the study was to evaluate the effect of two approaches to obesity treatment on the serum level of sex hormones in obese women of child-bearing age without PCOS. 77 obese Caucasian women (aged 31.2 ±8.3 years) were randomized into two groups: 39 women received a low-calorie diet (LC) and 38 received an isocaloric diet plus metformin (IM), for 12 weeks. Anthropometric parameters, body composition and serum concentrations of estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and dehydroepiandrosterone (DHEA-S) sulfate were evaluated at baseline and after the study. Reductions in body weight, body mass index (BMI), waist and body fat content with an increase  in lean body percent were significant and comparable between the LC and IM group after the trial. The concentrations of serum FSH, LH, E2, DHEA and T did not change in either group after treatment. A tendency towards an increase in the E2 concentration in both groups and a decrease in the T level in the LC group  was observed. The correlations between a change in BMI, fat content, waist-hip ratio and a change in T were documented in the LC group. A 12-week low-calorie diet and an isocaloric diet combined with metformin produced comparable and significant weight loss with improvements in body composition. Both interventions did not significantly affect FSH, LH and DHEA sulfate serum concentrations, only a trend towards an E2 increase and a T decrease was observed, stronger in LC group. The significant correlations shown between the changes in anthropometric and body composition parameters and T serum levels in women treated with a low-calorie diet alone show the beneficial effect of a lifestyle intervention on the sex hormone in obese premenopausal women.

Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients.

PubMed

Kebapcilar, Levent; Kebapcilar, Ayse Gul; Bilgir, Oktay; Taner, Cuneyt Eftal; Bozkaya, Giray; Yildiz, Yasar; Sari, Ismail

2011-02-01

To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing ethinyl oestradiol-cyproterone acetate (EE/CA) and metformin (M; 850 mg metformin twice a day) were given for three cycles. Plasma sCD40L was measured before and after the treatment of 3 months. At baseline, the sCD40L levels of the patients with PCOS was significantly higher than those of control subjects (3.1 ± 2.0 vs. 2.05 ± 1.0, respectively; p=0.002). An average of 3 months of EE/CA-M therapy induced a significant decrease of sCD40L levels in the PCOS group (3.1 ± 2.0 vs. 2.5 ± 1.0; p=0.026). After having treated patients with PCOS, the sCD40L level was not completely normalised when compared to the healthy controls (2.5 ± 1.0 vs. 2.05 ± 1.0; p=0.039). PCOS is associated with elevated levels of sCD40L. Adding metformin therapy to EE/CA may decrease sCD40L levels in women PCOS. However, after the treatment for PCOS subjects, the sCD40L was not completely normalised when compared patients to healthy controls.

Biomarkers and insulin sensitivity in women with Polycystic Ovary Syndrome: Characteristics and predictive capacity.

PubMed

Cassar, Samantha; Teede, Helena J; Harrison, Cheryce L; Joham, Anju E; Moran, Lisa J; Stepto, Nigel K

2015-07-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS. Cross-sectional study. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01). Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS. © 2014 John Wiley & Sons Ltd.

The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study.

PubMed

La Marca, Antonio; Grisendi, Valentina; Dondi, Giulia; Sighinolfi, Giovanna; Cianci, Antonio

2015-01-01

Polycystic ovary syndrome is characterized by irregular cycles, hyperandrogenism, polycystic ovary at ultrasound and insulin resistance. The effectiveness of D-chiro-inositol (DCI) treatment in improving insulin resistance in PCOS patients has been confirmed in several reports. The objective of this study was to retrospectively analyze the effect of DCI on menstrual cycle regularity in PCOS women. This was a retrospective study of patients with irregular cycles who were treated with DCI. Of all PCOS women admitted to our centre, 47 were treated with DCI and had complete medical charts. The percentage of women reporting regular menstrual cycles significantly increased with increasing duration of DCI treatment (24% and 51.6% at a mean of 6 and 15 months of treatment, respectively). Serum AMH levels and indexes of insulin resistance significantly decreased during the treatment. Low AMH levels, high HOMA index, and the presence of oligomenorrhea at the first visit were the independent predictors of obtaining regular menstrual cycle with DCI. In conclusion, the use of DCI is associated to clinical benefits for many women affected by PCOS including the improvement in insulin resistance and menstrual cycle regularity. Responders to the treatment may be identified on the basis of menstrual irregularity and hormonal or metabolic markers.

Binge eating behaviours and food cravings in women with Polycystic Ovary Syndrome.

PubMed

Jeanes, Y M; Reeves, S; Gibson, E L; Piggott, C; May, V A; Hart, K H

2017-02-01

Polycystic Ovary Syndrome (PCOS), the most common endocrine condition in women, is often anecdotally associated with binge eating behaviours and food cravings; however there is a paucity of research. This study aimed to report the prevalence of binge eating and food cravings and their relation to obesity risk in women with PCOS. Participants completed an online survey including the Bulimia Investigatory Test, Edinburgh, Food Cravings-Trait Questionnaire and the Three Factor Eating Questionnaire revised-18. The study included obese (n = 340), overweight (n = 70) and lean (n = 45) women with PCOS and lean healthy women (n = 40). Sixty percent of obese women with PCOS were categorised with binge-eating behaviour, with 39% presenting with clinically significant behaviour. Obese women with PCOS presented with high mean food cravings-trait scores (131.6 ± 28.9) that were significantly greater compared with lean (114.0 ± 34.9) and overweight women with PCOS (120.1 ± 29.5; p < 0.001). Multiple regression exploring relations between eating styles and adiposity explained 57% of the variance in binge eating symptom scores in women with PCOS (F = 130.4; p < 0.001, n = 463): significant predictors were food cravings total score (beta = 0.53; p < 0.001), emotional eating score (beta = 0.18; p < 0.001), body mass index (beta = 0.11; p < 0.001) and uncontrolled eating score (beta = 0.009; p = 0.02). Compared with lean healthy women, lean women with PCOS exhibited significantly higher binge eating symptom scores (10.9 ± 7.8 versus 7.4 ± 6.0; p < 0.05), though similar total food craving scores (114.0 ± 34.9 versus 105.6 ± 26.6: NS). This study is the largest, to date, to robustly report that a high proportion of women with PCOS exhibit binge eating behaviours. We recommend screening women with PCOS for binge eating behaviours to help inform the choice of weight management approach for this clinical population. Copyright © 2016

Significant Improvement Selected Mediators of Inflammation in Phenotypes of Women with PCOS after Reduction and Low GI Diet.

PubMed

Szczuko, Małgorzata; Zapałowska-Chwyć, Marta; Maciejewska, Dominika; Drozd, Arleta; Starczewski, Andrzej; Stachowska, Ewa

2017-01-01

Many researchers suggest an increased risk of atherosclerosis in women with polycystic ovary syndrome. In the available literature, there are no studies on the mediators of inflammation in women with PCOS, especially after dietary intervention. Eicosanoids (HETE and HODE) were compared between the biochemical phenotypes of women with PCOS (normal and high androgens) and after the 3-month reduction diet. Eicosanoid profiles (9( S )-HODE, 13( S )-HODE, 5( S )-HETE, 12( S )-HETE, 15( S )-HETE, 5( S )-oxoETE, 16( R )-HETE, 16( S )-HETE and 5( S ), 6( R )-lipoxin A 4 , 5( S ), 6( R ), 15( R )-lipoxin A 4 ) were extracted from 0.5 ml of plasma using solid-phase extraction RP-18 SPE columns. The HPLC separations were performed on a 1260 liquid chromatograph. No significant differences were found in the concentration of analysed eicosanoids in phenotypes of women with PCOS. These women, however, have significantly lower concentration of inflammatory mediators than potentially healthy women from the control group. Dietary intervention leads to a significant ( p < 0.01) increase in the synthesis of proinflammatory mediators, reaching similar levels as in the control group. The development of inflammatory reaction in both phenotypes of women with PCOS is similar. The pathways for synthesis of proinflammatory mediators in women with PCOS are dormant, but can be stimulated through a reduction diet. Three-month period of lifestyle change may be too short to stimulate the pathways inhibiting inflammatory process.

Significantly lengthened telomere in granulosa cells from women with polycystic ovarian syndrome (PCOS).

PubMed

Wei, Duo; Xie, Juanke; Yin, Baoli; Hao, Haoying; Song, Xiaobing; Liu, Qi; Zhang, Cuilian; Sun, Yingpu

2017-07-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. However, its etiology remains poorly understood. Recent studies indicated that telomere length was related to PCOS. However, the association between telomere length and PCOS has only been shown in leucocytes and remained controversial across different studies. To clarify the association between telomere length and PCOS, the current study interrogated telomere length not only in leucocytes, but also in follicular granulosa cells, which is essential for folliculogenesis and steroidogenesis. Seventy-five patients with PCOS and 81 controls with mechanical infertility undergoing their first in vitro fertilization cycle were enrolled. Their peripheral blood and granulosa cells were collected on the oocyte retrieval day. Telomere length of both leucocytes in the blood and granulosa cells was assayed by quantitative polymerase chain reaction. No significant difference was found in the leucocyte telomere length between controls and PCOS patients (0.99 ± 0.44 vs. 1.00 ± 0.38, p = 0.93). Interestingly, when comparing telomere length in granulosa cells between controls and PCOS subjects, significantly lengthened telomere length was found in PCOS subjects (1.00 ± 0.37 vs. 1.57±0.67, p < 0.0001). After adjustments for age and body mass index, the p value remained significant (p < 0.0001). This finding reinforced the association between telomere abnormalities and PCOS. Given the importance of telomere length in cellular proliferation, our findings provided novel insights into the pathophysiology of PCOS that abnormalities in telomere length possibly disturb folliculogenesis and subsequently result in PCOS.

Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations.

PubMed

Lunger, Fabian; Wildt, Ludwig; Seeber, Beata

2013-06-01

The aims of this cross-sectional study were to evaluate the relative agreement of both static and dynamic methods of diagnosing IR in women with polycystic ovary syndrome (PCOS) and to suggest a simple screening method for IR. All participants underwent serial blood draws for hormonal profiling and lipid assessment, a 3 h, 75 g load oral glucose tolerance test (OGTT) with every 15 min measurements of glucose and insulin, and an ACTH stimulation test. The prevalence of IR ranged from 12.2% to 60.5%, depending on the IR index used. Based on largest area under the curve on receiver operating curve (ROC) analyses, the dynamic indices outperformed the static indices with glucose to insulin ratio and fasting insulin (fInsulin) demonstrating the best diagnostic properties. Applying two cut-offs representing fInsulin extremes (<7 and >13 mIU/l, respectively) gave the diagnosis in 70% of the patients with high accuracy. Currently utilized indices for assessing IR give highly variable results in women with PCOS. The most accurate indices based on dynamic testing can be time-consuming and labor-intensive. We suggest the use of fInsulin as a simple screening test, which can reduce the number of OGTTs needed to routinely assess insulin resistance in women with PCOS.