The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis
TL;DR: It is suggested that prevention and treatment of obesity is important for the management of PCOS and central obesity was associated with higher fasting insulin levels.
Abstract: While many women with polycystic ovary syndrome (PCOS) are overweight, obese or centrally obese, the effect of excess weight on the outcomes of PCOS is inconsistent. The review aimed to assess the effects of overweight, obesity and central obesity on the reproductive, metabolic and psychological features of PCOS. MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting outcomes according to body mass index categories or body fat distribution. Data were presented as mean difference or risk ratio (95% confidence interval). This review included 30 eligible studies. Overweight or obese women with PCOS had decreased sex hormone-binding globulin (SHBG), increased total testosterone, free androgen index, hirsutism, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index and worsened lipid profile. Obesity significantly worsened all metabolic and reproductive outcomes measured except for hirsutism when compared to normal weight women with PCOS. Overweight women had no differences in total testosterone, hirsutism, total-cholesterol and low-density lipoprotein-cholesterol compared to normal weight women and no differences in SHBG and total testosterone compared to obese women. Central obesity was associated with higher fasting insulin levels. These results suggest that prevention and treatment of obesity is important for the management of PCOS.
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01 Jul 1989
TL;DR: It is suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria for ovarian polycystosis.
Abstract: Due to the comprehensive examination of 50 patients with ovarian polycystosis the authors suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria.
1,022 citations
TL;DR: The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life.
978 citations
TL;DR: The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues.
Abstract: Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
615 citations
Cites background from "The effect of obesity on polycystic..."
...Obesity can also exacerbate pre-existing clinical, hormonal, and metabolic features in women with PCOS (343)....
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...Obesity, fat distribution, and adipose tissue function and morphology It is well established that women with PCOS are often overweight or obese, and it is possible that the increasing global prevalence of obesity may play a key role in promoting the development of PCOS in susceptible individuals (343)....
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...The degree of weight loss (and the requisite time frame) necessary to induce significant improvement in the reproductive phenotype in women with PCOS remains poorly understood (343, 352)....
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TL;DR: Lifestyle intervention improves body composition, hyperandrogenism (high male hormones and clinical effects) and insulin resistance in women with PCOS, and provided benefits when compared to minimal treatment for secondary reproductive, anthropometric and reproductive outcomes.
Abstract: Background
Polycystic ovary syndrome (PCOS) affects 4% to 18% of reproductive-aged women and is associated with reproductive, metabolic and psychological dysfunction Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions
Objectives
To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS
Search methods
Electronic databases (Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL, AMED) (date of last search 7/9/2010), controlled trials register, conference abstracts, relevant journals, reference lists of relevant papers and reviews and grey literature databases, with no language restrictions applied
Selection criteria
Randomised controlled trials comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS
Data collection and analysis
Two authors independently selected trials, assessed methodological quality and risk of bias and extracted data
Main results
Six studies were included with n=164 participants Three studies compared physical activity to minimal dietary and behavioural advice or no advice Three studies compared combined dietary, exercise and behavioural interventions to minimal intervention Risk of bias varied with 4/6 having adequate sequence generation and clinician or outcome assessor blinding and 3/6 having adequate allocation concealment, complete outcome data and being free of selective reporting There were no studies assessing the fertility primary outcomes of pregnancy, live birth and miscarriage and no data for meta-analysis on ovulation or menstrual regularity Lifestyle intervention provided benefits when compared to minimal treatment for secondary reproductive, anthropometric and reproductive outcomes These included endpoint values for total testosterone (mean difference (MD) -027 nmol/L, 95% confidence interval (CI) -046 to -009, P = 0004), hirsutism or excess hair growth by the Ferriman-Gallwey score (MD -119, 95% CI -235 to -003, P = 004), weight (MD -347 kg, 95% CI -494 to -200, P < 000001), waist circumference (MD -195 cm, 95% CI -334 to -057, P = 0006) and fasting insulin (MD -202 µU/mL, 95% CI -328 to -077, P = 0002) There was no evidence of effect of lifestyle for body mass index, free androgen index, sex hormone binding globulin, glucose or cholesterol levels; and no data for quality of life, patient satisfaction or acne
Authors' conclusions
Lifestyle intervention improves body composition, hyperandrogenism (high male hormones and clinical effects) and insulin resistance in women with PCOS There was no evidence of effect for lifestyle intervention on improving glucose tolerance or lipid profiles and no literature assessing clinical reproductive outcomes, quality of life and treatment satisfaction
531 citations
TL;DR: A critical endocrine and European perspective on the debate on the definition of PCOS is offered and all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder are summarized.
Abstract: Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
491 citations
References
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01 Jan 2014
TL;DR: The Newcastle-Ottawa Scale (NOS) as discussed by the authors was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results.
Abstract: Nonrandomised studies, including case-control and cohort studies, can be challenging to implement and conduct. Assessment of the quality of such studies is essential for a proper understanding of nonrandomised studies. The Newcastle-Ottawa Scale (NOS) is an ongoing collaboration between the Universities of Newcastle, Australia and Ottawa, Canada. It was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results. A 'star system' has been developed in which a study is judged on three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively. The goal of this project is to develop an instrument providing an easy and convenient tool for quality assessment of nonrandomised studies to be used in a systematic review.
17,590 citations
"The effect of obesity on polycystic..." refers methods in this paper
...The assessment criteria were based on the Newcastle–Ottawa scale for observational studies (49)....
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...Quality of the included studies was assessed using criteria based on the Newcastle–Ottawa scale for non-randomized studies (49)....
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TL;DR: In this paper, the authors compared a lifestyle intervention with metformin to prevent or delay the development of Type 2 diabetes in nondiabetic individuals. And they found that the lifestyle intervention was significantly more effective than the medication.
Abstract: Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
17,333 citations
TL;DR: The increases in the prevalence of obesity previously observed do not appear to be continuing at the same rate over the past 10 years, particularly for women and possibly for men.
Abstract: Results In 2007-2008, the age-adjusted prevalence of obesity was 33.8% (95% confidence interval [CI], 31.6%-36.0%) overall, 32.2% (95% CI, 29.5%-35.0%) among men, and 35.5% (95% CI, 33.2%-37.7%) among women. The corresponding prevalence estimates for overweight and obesity combined (BMI 25) were 68.0% (95% CI, 66.3%-69.8%), 72.3% (95% CI, 70.4%-74.1%), and 64.1% (95% CI, 61.3%66.9%). Obesity prevalence varied by age group and by racial and ethnic group for both men and women. Over the 10-year period, obesity showed no significant trend among women (adjusted odds ratio [AOR] for 2007-2008 vs 1999-2000, 1.12 [95% CI, 0.89-1.32]). For men, there was a significant linear trend (AOR for 2007-2008 vs 1999-2000, 1.32 [95% CI, 1.12-1.58]); however, the 3 most recent data points did not differ significantly from each other.
7,730 citations
"The effect of obesity on polycystic..." refers background or methods in this paper
...(2) Representativeness of the cases: (a) consecutive or obviously representative series of cases*,...
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...(2) Same method of ascertainment for cases and controls: (a) yes*, (b) no....
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TL;DR: These recommendations recognize the importance of social and environmental change to reduce the obesity epidemic but also identify ways healthcare providers and health care systems can be part of broader efforts.
Abstract: To revise 1998 recommendations on childhood obesity, an Expert Committee, comprised of representatives from 15 professional organizations, appointed experienced scientists and clinicians to 3 writing groups to review the literature and recommend approaches to prevention, assessment, and treatment. Because effective strategies remain poorly defined, the writing groups used both available evidence and expert opinion to develop the recommendations. Primary care providers should universally assess children for obesity risk to improve early identification of elevated BMI, medical risks, and unhealthy eating and physical activity habits. Providers can provide obesity prevention messages for most children and suggest weight control interventions for those with excess weight. The writing groups also recommend changing office systems so that they support efforts to address the problem. BMI should be calculated and plotted at least annually, and the classification should be integrated with other information such as growth pattern, familial obesity, and medical risks to assess the child’s obesity risk. For prevention, the recommendations include both specific eating and physical activity behaviors, which are likely to promote maintenance of healthy weight, but also the use of patient-centered counseling techniques such as motivational interviewing, which helps families identify their own motivation for making change. For assessment, the recommendations include methods to screen for current medical conditions and for future risks, and methods to assess diet and physical activity behaviors. For treatment, the recommendations propose 4 stages of obesity care; the first is brief counseling that can be delivered in a health care office, and subsequent stages require more time and resources. The appropriateness of higher stages is influenced by a patient’s age and degree of excess weight. These recommendations recognize the importance of social and environmental change to reduce the obesity epidemic but also identify ways healthcare providers and health care systems can be part of broader efforts.
4,272 citations
"The effect of obesity on polycystic..." refers methods in this paper
...For adolescents, age–gender specific percentile distributions for BMI in the Centers for Disease Control and Prevention growth charts were used to identify those who were overweight (85th–95th percentile) or obese (>95th percentile) (47)....
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TL;DR: Results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
Abstract: Tumor necrosis factor-α (TNF-α) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor (IR). Treatment of cultured murine adipocytes with TNF-α was shown to induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant to TNF-α-mediated inhibition of IR signaling, whereas transfected 32D cells that express IRS-1 were very sensitive to this effect of TNF-α. An inhibitory form of IRS-1 was observed in muscle and fat tissues from obese rats. These results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
2,578 citations