Polycystic ovary syndrome.

University of Chicago, Department of Medicine, Section of Endocrinology, Chicago, USA.
New England Journal of Medicine (Impact Factor: 54.42). 04/2005; 352(12):1223-36. DOI: 10.1056/NEJMra041536
Source: PubMed
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    ABSTRACT: Contraceptive hormones, most commonly prescribed as oral contraceptives (OCs), are a widely utilized method to prevent ovulation, implantation, and, therefore, pregnancy. The Women's Health Initiative demonstrated cardiovascular risk linked to menopausal hormone therapy among women without pre-existing cardiovascular disease, prompting a review of the safety, efficacy, and side effects of other forms of hormone therapy. A variety of basic science, animal, and human data suggests that contraceptive hormones have antiatheromatous effects; however, relatively less is known regarding the impact on atherosclerosis, thrombosis, vasomotion, and arrhythmogenesis. Newer generation OC formulations in use indicate no increased myocardial infarction risk for current users, but a persistent increased risk of venous thromboembolism. There are no cardiovascular data available for the newest generation contraceptive hormone formulations, including those that contain newer progestins that lower blood pressure, as well as the nonoral routes (transdermal and vaginal). Current guidelines indicate that, as with all medication, contraceptive hormones should be selected and initiated by weighing risks and benefits for the individual patient. Women 35 years and older should be assessed for cardiovascular risk factors including hypertension, smoking, diabetes, nephropathy, and other vascular diseases, including migraines, prior to use. Existing data are mixed with regard to possible protection from OCs for atherosclerosis and cardiovascular events; longer-term cardiovascular follow-up of menopausal women with regard to prior OC use, including subgroup information regarding adequacy of ovulatory cycling, the presence of hyperandrogenic conditions, and the presence of prothrombotic genetic disorders is needed to address this important issue.
    Journal of the American College of Cardiology 02/2009; 53(3):221-31. · 14.09 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is a heterogeneous condition with unknown aetiology which is considered to be the most common endocrine disorder in women of reproductive age. In this work we investigated the association of insulin receptor (IotaNSR) and insulin receptor substrates (IRSs) polymorphisms with the risk of developing PCOS. The meta-analysis of eleven studies (889 cases, 1303 controls) yielded a significant association for IRS-1 Gly972Arg (G972R) polymorphism concerning the GR vs. GG genotype (OR: 1.77, 95% CI: 1.28, 2.45), with no between-studies heterogeneity. Concerning IotaNSR His1058 C/T, the meta-analysis of eight studies (795 cases, 576 controls) found no significant evidence for association with PCOS (OR for the TT+CT vs. CC comparison equal to 1.28 with 95% CI: 0.88, 1.85) and a moderate between studies variability (I(2)=44.6%). No evidence for publication bias was found in these meta-analyses. Following a multivariate Mendelian randomization approach, the overall OR was unaffected but the overall mean difference of fasting insulin levels between carriers of GR and RR genotypes in controls was significant (2.18, 95% CI: 0.36, 4.01). These results suggest that IRS-1 Gly972Arg polymorphism is significantly associated with the risk of developing PCOS and that this association is primarily mediated by increasing the levels of fasting insulin. The particular polymorphism is located in a region nearby two phosphorylation sites that interact physically with INSR and PI 3-kinase and there is enough evidence from the literature suggesting that the Arg972 variant is associated with decreased PI 3-kinase activity and impaired insulin-stimulated signaling.
    Molecular Genetics and Metabolism 10/2009; 99(2):174-83. · 2.83 Impact Factor
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