Cardiometabolic abnormalities in the polycystic ovary syndrome: Pharmacotherapeutic insights

ArticleinPharmacology [?] Therapeutics 119(3):223-41 · July 2008with12 Reads
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.
    • "As we have shown (Nikolic et al., 2014) treatment of juvenile rats with DHT induces both reproductive and metabolic abnormalities similar to those seen in women with PCOS. Growing body of evidence supports a notion that women with PCOS display an increased prevalence of cardiovascular disease risk factors (Westerveld et al., 2008). Women with PCOS have increased arterial lesions in their coronary vessels (Birdsall et al., 1997), while data on increased frequency of myocardial infarction in PCOS women are controversial (Schmidt et al., 2011; Mani et al., 2013; Iftikhar et al., 2012; Dahlgren et al., 1992). "
    [Show abstract] [Hide abstract] ABSTRACT: Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1 177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning. © Georg Thieme Verlag KG Stuttgart · New York.
    Full-text · Article · May 2015
    • "Although not part of the diagnostic criteria for PCOS, insulin resistance is considered to play a key role in the aetiology of PCOS. Moreover, insulin resistance is associated with metabolic abnormalities (Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group, 2012) such as metabolic syndrome (Essah et al., 2007 ), dyslipidaemia (Westerveld et al., 2008), gestational diabetes (Boomsma et al., 2006) and type 2 diabetes (Legro et al., 1999). Debate continues whether women with PCOS, despite their adverse cardiometabolic profile, are indeed at increased risk of cardiovascular disease later in life (Fauser and Bouchard, 2011). "
    [Show abstract] [Hide abstract] 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.
    Article · Jun 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, characterized by anovulation, hyperandrogenism and polycystic ovaries at ultrasonography. In addition to its reproductive consequences, PCOS is associated with metabolic abnormalities of which altered sensitivity to insulin appears to play a pivotal role in the development of the disorder. Currently, PCOS is considered to be a developmental disorder with varying clinical presentations depending on age. This review provides an overview of the manifestations associated with PCOS from preconception until the post-reproductive years.
    Article · Nov 2008
Show more