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Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.
Gunning, MN, Sir Petermann, T, Crisosto, N, van Rijn, BB, de Wilde, MA, Christ, JP, Uiterwaal, CSPM, de Jager, W, Eijkemans, MJC, Kunselman, AR, et al
Human reproduction update. 2020;(1):103-117
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Abstract
BACKGROUND Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome. OUTCOMES Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (β = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (βf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = -0.31(95%CI: -0.57 to 0.06), βm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.
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Effects of inositol and alpha lipoic acid combination for polycystic ovary syndrome: A protocol for systematic review and meta-analysis.
Lei, W, Gao, Y, Hu, S, Liu, D, Chen, Q
Medicine. 2020;(30):e20696
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Abstract
BACKGROUND Polycystic ovary syndrome (PCOS), an intricate and multifactorial disease, has characteristics of diverse clinical, metabolic and endocrine disorder. It represents a primary cause of infertility in reproductive women, which seriously affects the physical and mental health of patients. Several small studies have indicated that inositol and alpha lipoic acid (ALA) supplementation can ameliorate the outcomes in terms of menstrual cyclicity, ovulation and hyperinsulinemia in PCOS women. However, there is a lack of sufficient evidence to affirm this practice. Consequently, we aim to objectively review and estimate the efficacy and safety of inositol plus ALA in adult women suffering from PCOS. METHODS AND ANALYSIS We will retrieve PubMed, EMBASE, The Web of Science, The Cochrane Library of Controlled Trials, Clinical Trials.gov, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wan-Fang database with no specific limitations on language. Simultaneously we will manually retrieve reference lists and grey literature to acquire potential eligibility. We will restrict our search to randomized controlled trials (RCTs) of inositol in combination with ALA for PCOS. Researchers will separately identify studies, extract data and evaluate the quality of studies. We will conduct risk of bias estimates, data synthesis and analysis using Review Manager 5.3 software. RESULTS AND CONCLUSION The study will comprehensively determine the effectiveness and safety of inositol conjunct with ALA therapy for PCOS. Meanwhile we intend to disseminate the final findings in a peer-reviewed journal to help patients, clinicians and health policymakers select treatment strategy of PCOS by providing high-quality evidence.
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The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial.
Haidari, F, Banaei-Jahromi, N, Zakerkish, M, Ahmadi, K
Nutrition journal. 2020;(1):8
Abstract
BACKGROUND Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS. METHODS This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study. RESULTS The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p < 0.05). Flaxseed supplementation also led to a significant reduction in insulin concentration, HOMA-IR, TG, hs-CRP, Interleukin 6 (IL- 6), and leptin and an increase in QUICKI, HDL, and adiponectin compared to the control group (p < 0.05). No significant changes were observed in other parameters. CONCLUSIONS Flaxseed supplementation plus lifestyle modification was more effective compared to lifestyle modification alone in biochemical and anthropometric variables in patients with PCOS. TRIAL REGISTRATION The trial protocol was approved by the Ethics Board at Ahvaz Jundishapur University of Medical Sciences and was registered at Iranian Registry of Clinical Trials (code: IRCT20120704010181N11).
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Supervised exercise training and increased physical activity to reduce cardiovascular disease risk in women with polycystic ovary syndrome: study protocol for a randomized controlled feasibility trial.
Woodward, A, Broom, D, Dalton, C, Metwally, M, Klonizakis, M
Trials. 2020;(1):101
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) affects up to 20% of women and is characterised by higher amounts of visceral fat, obesity, insulin resistance, dyslipidemia and reproductive and cardiometabolic complications. Increased oxidised low-density lipoprotein (LDL) concentrations have been associated with an increased risk of cardiovascular disease (CVD)-related events. Oxidised LDL is rarely used as a marker for CVD risk in PCOS-related studies despite its widely accepted role in atherogenesis and the increased risk factors associated with PCOS. Additionally, prolonged periods of sedentary behaviour can negatively affect metabolic health. No studies have specifically examined the effects of reducing sedentary behaviour on CVD risk in PCOS with a lifestyle physical activity intervention. The aim of the current study is to measure the feasibility of a randomised controlled trial (RCT) examining the effects of supervised exercise and reducing sedentary behaviour in women with PCOS on CVD risk. METHODS/DESIGN A feasibility, exploratory RCT will be conducted. Fifty-one pre-menopausal females will be randomly allocated between an exercise group (EG), a lifestyle physical activity group (LPAG) and a control group. Participants in the EG will undertake a 12-week supervised aerobic exercise programme. The LPAG will aim to increase daily physical activity and reduce sedentary behaviour for 12 weeks. The control group will not take part in any intervention. Primary outcomes are feasibility and acceptability of the intervention and procedures. Secondary outcomes are oxidised LDL, aerobic fitness, blood lipid profile, fasting glucose and insulin, testosterone and inflammatory markers. DISCUSSION PCOS is associated with various increased risk factors for CVD, including hypertension, dyslipidemia, abdominal obesity, insulin resistance, and inflammation. Whether oxidised LDL has a role in this increased risk is not yet known. The present study aims to measure the feasibility of implementing structured exercise training and/or increased lifestyle physical activity in women with PCOS, so that a subsequent adequately powered RCT can be designed. The results from the study will be used to refine the interventions and determine the acceptability of the study design. A limitation is that some self-monitoring in the lifestyle physical activity group may not be reliable or replicable, for example inputting information about time spent cleaning/gardening. TRIAL REGISTRATION ClinicalTrials.gov, NCT03678714. Registered 20 September 2018.
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Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis.
Pearsey, HM, Henson, J, Sargeant, JA, Davies, MJ, Khunti, K, Suzuki, T, Bowden-Davies, KA, Cuthbertson, DJ, Yates, TE
Reviews in endocrine & metabolic disorders. 2020;(4):569-575
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Abstract
To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L-1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (-4.14 [-8.17, -0.11] mg.L-1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (-0.30 [-3.67, 3.07] mg. L-1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn.
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Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis.
Kite, C, Lahart, IM, Afzal, I, Broom, DR, Randeva, H, Kyrou, I, Brown, JE
Systematic reviews. 2019;(1):51
Abstract
BACKGROUND Typically, management of PCOS focuses on lifestyle changes (exercise and diet), aiming to alleviate symptoms, and lower the associated risk of type 2 diabetes and cardiovascular disease. Our objective was to analyse evidence on the effectiveness of exercise in the management of PCOS, when compared to (i) usual care, (ii) diet alone, and (iii) exercise combined with diet, and also exercise combined with diet, compared to (i) control or usual care and (ii) diet alone. METHODS Relevant databases were searched (June 2017) with no time limit for trial inclusion. Eligible trials employed a randomised or quasi-randomised design to measure the chronic effects of exercise, or exercise and diet in women with PCOS. RESULTS Searches returned 2390 articles; of those, 27 papers from 18 trials were included. Results are presented as mean difference (MD) and 95% confidence intervals (95% CI). Compared with control, exercise had a statistical effect on change from baseline fasting insulin (MD - 2.44 μIU/mL, 95% CIs - 4.24 to - 0.64; very low-quality evidence), HOMA-IR (- 0.57, - 0.99 to - 0.14; very low-quality evidence), total cholesterol (- 5.88 mg/dL, - 9.92 to - 1.83; low-quality evidence), LDL cholesterol (- 7.39 mg/dL, - 9.83 to - 4.95; low-quality evidence), and triglycerides (- 4.78 mg/dL, - 7.52 to - 2.05; low-quality evidence). Exercise also improved VO2 max (3.84 ml/kg/min, 2.87 to 4.81), waist circumference (- 2.62 cm, - 4.13 to - 1.11), and body fat percentage (- 1.39%, - 2.61 to - 0.18) when compared with usual care. No effect was found for change value systolic/diastolic blood pressure, fasting glucose, HDL cholesterol (all low-quality evidence), or waist-to-hip ratio. Many favourable change score findings were supported by post-intervention value analyses: fasting insulin (- 2.11 μIU/mL, - 3.49 to - 0.73), total cholesterol (- 6.66 mg/dL, - 11.14 to - 2.17), LDL cholesterol (- 6.91 mg/dL, - 12.02 to - 1.80), and VO2 max (5.01 ml/kg/min, 3.48 to 6.54). Statistically lower BMI (- 1.02 kg/m2, - 1.81 to - 0.23) and resting heart rate (- 3.26 beats/min - 4.93 to - 1.59) were also revealed in post-intervention analysis. Subgroup analyses revealed the greatest improvements in overweight/obese participants, and more outcomes improved when interventions were supervised, aerobic in nature, or of a shorter duration. Based on limited data, we found no differences for any outcome between the effects of exercise and diet combined, and diet alone. It was not possible to compare exercise vs diet or exercise and diet combined vs diet. CONCLUSION Statistically beneficial effects of exercise were found for a range of metabolic, anthropometric, and cardiorespiratory fitness-related outcomes. However, caution should be adopted when interpreting these findings since many outcomes present modest effects and wide CIs, and statistical effects in many analyses are sensitive to the addition/removal of individual trials. Future work should focus on rigorously designed, well-reported trials that make comparisons involving both exercise and diet. SYSTEMATIC REVIEW REGISTRATION This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Reviews ( CRD42017062576 ).
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Nonpharmacologic Management of Symptoms in Females With Polycystic Ovary Syndrome: A Narrative Review.
Speelman, DL
The Journal of the American Osteopathic Association. 2019;(1):25-39
Abstract
Polycystic ovary syndrome is the most common hormone disorder in females of reproductive age, affecting reproductive, metabolic, and cardiovascular health. With an unknown cause and a spectrum of common signs and symptoms, diagnosis is based on consensus criteria, and treatment options often target individual symptoms, with variable effectiveness. Safe, effective complementary and alternative therapies can be used to manage symptoms. The first-line intervention is lifestyle modification, including weight loss when appropriate, with caloric restriction and exercise to maintain a healthy weight. Low-carbohydrate and/or low-glycemic index diets can provide additional benefits, and nutritional supplements may be useful adjuncts. The recommended physical activity regimen should include both aerobic and resistance exercise.
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A comprehensive review of clinical studies with herbal medicine on polycystic ovary syndrome (PCOS).
Moini Jazani, A, Nasimi Doost Azgomi, H, Nasimi Doost Azgomi, A, Nasimi Doost Azgomi, R
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences. 2019;(2):863-877
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BACKGROUND Polycystic ovary syndrome (PCOS) is a frequent medical condition characterized by both metabolic and reproductive disorders. Different pharmaceutical treatments have been proposed for PCOS. However, side effects of long-term treatments and their probable low efficacy have made complementary and alternative treatments a valuable option. Recent reports have indicated the increased use of complementary treatments. Herbal medicine, as part of complementary medicine, was find introduced in traditional Persian and Chinese medicine. Medicinal herbs have used for a long time in the treatment of gynecological and infertility problems of PCOS patients. In this study, we aimed to review herbal medicines used for PCOS worldwide. METHODS PubMed, Embase, Cochrane, and Scopus databases were searched for clinical trials and Randomized Controlled Trials based on related keywords. Data were collected from 1990 to 2019. RESULTS According to a multitude of studies, a wide spectrum of herbs can be used to improve various aspects of PCOS. Herbs such as Cinnamomum verum, Trigonella foenum-graecum L., and Vitex agnus-castus can impact on menstrual and ovulatory dysfunctions, obesity, insulin resistance, lipid-metabolism dysfunction, and androgen excess-related conditions. CONCLUSION Some plants as natural remedies may have beneficial effects on improving different aspects of PCOS; but further studies are needed to investigate their mechanisms and safety.
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Pathomechanisms of polycystic ovary syndrome: Multidimensional approaches.
Sagvekar, P, Dadachanji, R, Patil, K, Mukherjee, S
Frontiers in bioscience (Elite edition). 2018;(3):384-422
Abstract
Polycystic ovary syndrome is a complex endocrine disorder affecting numerous women of reproductive age across the globe. Characterized mainly by irregular menses, hirsutism, skewed LH: FSH ratios and bulky polycystic ovaries, this multifactorial endocrinopathy results in unfavorable reproductive and metabolic sequelae, including anovulatory infertility, type 2 diabetes, metabolic syndrome and cardiovascular disease in later years. Increasing evidence has shown that the manifestation of polycystic ovary syndrome (PCOS) is attributable to a cumulative impact of altered genetic, epigenetic and protein profiles which bring about a systemic dysfunction. While genetic approaches help ascertain role of causal variants in its etiology, tissue-specific epigenetic patterns help in deciphering the auxiliary role of environmental, nutritional and behavioral factors. Proteomics is advantageous, linking both genotype and phenotype and contributing to biomarker discovery. Investigating molecular mechanism underlying PCOS is imperative in order to gain insight into the pathophysiology of PCOS and formulate novel diagnostic and treatment strategies. In this review we have summarized these three aspects, which have been successfully utilized to delineate the pathomechanisms of PCOS.
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The effects of vitamin D supplementation on metabolic profiles and gene expression of insulin and lipid metabolism in infertile polycystic ovary syndrome candidates for in vitro fertilization.
Dastorani, M, Aghadavod, E, Mirhosseini, N, Foroozanfard, F, Zadeh Modarres, S, Amiri Siavashani, M, Asemi, Z
Reproductive biology and endocrinology : RB&E. 2018;(1):94
Abstract
BACKGROUND Vitamin D deficiency in women diagnosed with polycystic ovary syndrome (PCOS) remarkably decreases the chance of pregnancy, which might be related to its impact on metabolic abnormalities in these patients. It is hypothesized that vitamin D supplementation influences metabolic profile of these patients and indirectly might affect fertility and the outcomes. Therefore, this study was conducted to determine the effects of vitamin D supplementation on the levels of anti-Müllerian hormone (AMH), metabolic profiles, and gene expression of insulin and lipid metabolism in infertile women with PCOS who were candidate for in vitro fertilization (IVF). METHODS This study was a randomized, double-blinded, placebo-controlled trial conducted among 40 infertile women, aged 18-40 years, diagnosed with PCOS and was candidate for IVF. Participants were randomly assigned into two intervention groups for receiving either 50,000 IU vitamin D or placebo (n = 20 each group) every other week for 8 weeks. Gene expression for insulin and lipid metabolism was conducted using peripheral blood mononuclear cells (PBMCs) of women with PCOS, via RT-PCR method. RESULTS Vitamin D supplementation led to a significant reduction in serum AMH (- 0.7 ± 1.2 vs. - 0.1 ± 0.5 ng/mL, P = 0.02), insulin levels (- 1.4 ± 1.6 vs. -0.3 ± 0.9 μIU/mL, P = 0.007), homeostatic model of assessment for insulin resistance (- 0.3 ± 0.3 vs. -0.1 ± 0.2, P = 0.008), and a significant increase in quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. + 0.001 ± 0.004, P = 0.04), compared with the placebo. Moreover, following vitamin D supplementation there was a significant decrease in serum total- (- 5.1 ± 12.6 vs. + 2.9 ± 10.9 mg/dL, P = 0.03) and LDL-cholesterol levels (- 4.5 ± 10.3 vs. + 2.5 ± 10.6 mg/dL, P = 0.04) compared with the placebo. CONCLUSION Overall, the findings of this trial supported that 50,000 IU vitamin D supplementation every other week for 8 weeks had beneficial effects on insulin metabolism, and lipid profile of infertile women with PCOS who are candidate for IVF. These benefits might not be evident upon having sufficient vitamin D levels. TRIAL REGISTRATION This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT20170513033941N27).