Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights.

Department of Internal Medicine, University Medical Center Utrecht, The Netherlands.
Pharmacology [?] Therapeutics (Impact Factor: 7.79). 07/2008; 119(3):223-41. DOI: 10.1016/j.pharmthera.2008.04.009
Source: PubMed

ABSTRACT The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam criteria). PCOS is associated with obesity, insulin resistance and dyslipidemia. Different patterns of dyslipidemia can be present, both in lean and obese PCOS. Low HDL-cholesterol, with or without elevated TG, is the most prominent lipid abnormality. In addition, smaller HDL and LDL particles and elevated postprandial TG responses are reported. Hyperandrogenism, anovulation and insulin resistance affect multiple steps in lipid metabolism in PCOS, as will be discussed. Surrogate markers for atherosclerosis are consistently abnormal in PCOS, while studies on clinical CVD endpoints are limited and non-conclusive. The (pharmaco-) therapy of dyslipidemia in PCOS will be discussed. In addition, the effects of other PCOS related (pharmaco-) therapies, primarily aimed at hyperandrogenism, anovulation or insulin resistance, on lipid metabolism will be addressed.

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    ABSTRACT: PURPOSE OF REVIEW: Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in premenopausal women. This review discusses the screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with PCOS, highlighting significant recent developments. RECENT FINDINGS: PCOS is a complex genetic disorder with multiple susceptibility genes as well as environmental factors influencing the expression of various PCOS phenotypes. The first genome-wide association study of PCOS identified susceptibility loci on chromosome 2 near the luteinizing hormone receptor gene LHCGR and chromosome 9 near the obesity gene DEEND1A. Women with PCOS are affected by a variety of metabolic disorders, including insulin resistance, metabolic syndrome, type-2 diabetes, dyslipidemia and obesity. Recently, it has been established that women with PCOS have a high risk of nonalcoholic fatty liver disease. These metabolic disturbances are associated with an increased risk of cardiovascular disease (CVD). Although women with PCOS have higher rates of cardiovascular risk factors and intermediate markers of CVD, studies definitively documenting increased CVD are lacking. SUMMARY: The high prevalence of metabolic disorders and CVD risk factors in women with PCOS highlights the need for early screening, diagnosis and treatment of these disorders to promote long-term health and possibly prevent CVD.
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    ABSTRACT: STUDY QUESTION: Is routine screening by oral glucose tolerance test (OGTT) needed for all women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Screening for glucose metabolism abnormalities of PCOS patients by an OGTT could potentially be limited to patients who present with a fasting glucose concentration between 6.1 and 7.0 mmol/l only. WHAT IS KNOWN ALREADY: Women with PCOS are at increased risk of developing diabetes. This study proposes a stepwise screening strategy for (pre)diabetes for PCOS patients based on risk stratification by fasting plasma glucose. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 226 women diagnosed with anovulatory PCOS. PARTICIPANTS AND SETTING: A consecutive series of 226 patients, diagnosed with PCOS at the University Medical Centre Utrecht, the Netherlands, were screened for glucose metabolism abnormalities by OGTT (75 g glucose load). MAIN RESULTS AND ROLE OF CHANCE: The majority of the 226 women (mean age: 29.6 ± 4.3 years; BMI: 27.3 ± 6.7 kg/m(2); 81% Caucasian) presented with a normal OGTT (169 women (75%)). Of the 57 (25%) women presenting with mild to moderate glucose abnormalities, 53 (93%) could be identified by fasting glucose concentrations only. Diabetes was diagnosed in a total of eight women (3.5%). In six women, the diagnosis was based on fasting glucose >7.0 mmol/l. The other two cases of diabetes initially presented with fasting glucose between 6.1 and 7.0 mmol/l and were diagnosed by OGTT assessment. No women diagnosed with diabetes presented with fasting glucose levels below 6.1 mmol/l. We therefore conclude that all diabetes patients could potentially be found by initial fasting glucose assessment followed by OGTT only in patients with fasting glucose between 6.1 and 7.0 mmol/l. LIMITATIONS, REASONS FOR CAUTION: Before general implementation can be advised, this screening algorithm should be validated in a prospective study of a similar or greater number of PCOS women. WIDER IMPLICATIONS OF THE FINDINGS: Our study comprised of a mostly Caucasian (81%) population, therefore generalization to other ethnic populations should be done with caution. STUDY FUNDING/COMPETING INTEREST(S): No external finance was involved in this study. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. A.J.G. has received fees from Abbott, Bayer Schering and IBSA. T.W.H. has received fees from Merck, Sharpe & Dohme, GlaxoSmithKline, NovoNordisk and Eli Lilly. The authors declare complete independence from funders. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5% to 10% of women worldwide. Approximately half of women with PCOS are lean, yet may still present with central obesity and metabolic disturbances. Low-glycemic index (GI) dietary intervention studies have demonstrated improvements in insulin sensitivity in insulin-resistant populations; however, there is little evidence of this effect in women with PCOS. This research aimed to determine the efficacy of an isocaloric low-GI dietary intervention on insulin sensitivity, independent of weight change, in women with PCOS. A nonrandomized 12-week low-GI dietary intervention, preceded by a 12-week habitual diet control phase and proceeded by a 12-week follow-up phase was conducted. Dietary intake, body composition, and metabolic risk markers were determined at baseline, after completion of the habitual diet control phase, and after the low-GI dietary intervention. Twenty-six participants were recruited at baseline, 22 commenced and 21 participants completed the low-GI dietary intervention phase. The primary outcome was change in insulin sensitivity. Secondary outcomes included assessment of changes to lipids, body composition, and estimated macronutrient intake. Repeated measures analysis of variance with Bonferroni correction were used to detect changes to outcomes across study timepoints. Twenty-one women with PCOS with mean (± standard deviation) age of 32.1±6.7 years completed the 12-week low-GI dietary intervention. As expected, no significant changes occurred during the 12-week habitual diet control phase. However, during the dietary intervention phase, dietary GI decreased from 54.5± 3.5 to 48.6±5.1 (P<0.001) with a concurrent small reduction in saturated fat intake (12.4%±3% to 11.7%±3% contribution from energy, P=0.03), despite no specific recommendations to modify fat intake. Measures of insulin sensitivity and nonesterified fatty acid improved after intervention (P=0.03 and P=0.01, respectively). This is the first study to implement an isocaloric low-GI diet in women with PCOS and findings may contribute to the limited research in this area.
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