European Congress of Endocrinology media release

Embargoed until 00:01CEST, Monday 2 May 2011

Blood test markers link polycystic ovary syndrome with cardiovascular risk
A new study presented at the European Congress of Endocrinology shows that women with polycystic ovary syndrome (PCOS) show higher levels of blood markers associated with cardiovascular disease (CVD) than control groups. These markers show up during a womans earlier life, but might indicate a greater CVD risk in later life. PCOS is a common ailment, affecting between 5-10% of women of reproductive age, meaning that there are millions of PCOS sufferers in Europe. Symptoms vary, but women with PCOS can suffer from ovarian cysts, irregular (or missing) periods, acne, higher than normal androgen levels and excess facial and body hair. PCOS may be associated with obesity and/or insulin resistance and is also one of the main causes of female infertility. Past studies have shown no conclusive link between PCOS and these risk markers. Doctors can test for cardiovascular risk markers during the normal reproductive period of a womans life. These markers dont directly predict cardiovascular risk, but higher levels of these markers are associated with cardiovascular risk in the future. This means that women with raised levels of these markers will, in later years, tend to have a higher rate of cardiovascular disease than is found in the general population. Working at the Aristotle University of Thessaloniki, Greece, Dr Konstantinos Toulis and coworkers Assistant Professor Dimitrios Goulis and Professor Basil Tarlatzis, carried out a major study of studies (meta-analysis) on risk markers for cardiovascular disease in women with PCOS. They reviewed 130 previous studies, involving in total 6260 women with PCOS and 4546 controls. They looked at whether the levels of biochemical blood markers for CVD differed in women with PCOS compared to controls. They found that 7 of the 10 markers they looked at were elevated in women with PCOS (see table below), meaning that these women might be more susceptible to developing heart disease. As yet the researchers dont know if these elevated risk markers lead directly to a higher level of heart disease in PCOS women, but this is the next thing they hope to investigate.

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Researcher Dr Konstantinos Toulis said: This analysis shows that increased levels of risk markers for cardiovascular disease are firmly associated with PCOS. PCOS is a difficult condition to study, because the range and severity of symptoms vary so much that it has been difficult to draw conclusions. Recently an expert panel1 reviewed the evidence and concluded that women with PCOS did seem to have an elevated risk of cardiovascular disease in later life. This meta-analysis of biochemical markers shows that the CVD risk factors are present in earlier life, and that they seem to be independent of other factors which can lead to cardiovascular disease in later life, such as obesity. The association between CVD risk and CVD markers depends on the nature of the individual marker and the magnitude of the difference; this, plus the fact that there are several of these biochemical markers raised, is what makes this a potential warning. Cardiovascular disease is the number one cause of death for women in the western world, and as so many women suffer from PCOS, then any increase in cardiovascular disease risk may translate into later problems for an appreciable amount of women. We need to remember that at the moment this is just an association between the biochemical markers and cardiovascular disease in PCOS women, rather than proof of a cause and effect. We do need to follow this up by looking at women with PCOS and cardiovascular disease, and seeing if they had shown higher levels of the risk markers. ----------Ends---------Notes for editors
Summary of outcomes for markers tested Cardiovascular risk marker tested CRP (C-reactive protein) Hcy (Homocysteine) PAI-1 Antigen (Plasminogen activator inhibitor-1 antigen PAI-1 activity Plasminogen activator inhibitor-1 activity) VEGF (Vascular endothelial growth factor) ADMA (Asymmetric dimethylarginine) AGE (Advanced glycation end products) TNF- (Tumour-necrosis factor ) Fibrinogen IL-6 (Interleukin-6) Result in women with PCOS Raised to significant level Raised to significant level Raised to significant level Raised to significant level Raised to significant level Raised to significant level Raised to significant level Raised, but borderline significance Raised, but borderline significance Non-significant

Reference 1 Assessment of Cardiovascular Risk and Prevention of Cardiovascular Disease in Women with the Polycystic Ovary Syndrome: A Consensus Statement by the Androgen Excess and Polycystic Ovary Syndrome, (AE-PCOS) Society. R Wild et at, J. Clin. Endocrinol. Metab. 2010 95:2038-2049 originally published online Apr 7, 2010; doi: 10.1210/jc.2009-2724

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The poster (number 99) will be presented at the European Congress of Endocrinology at 17:40-18:30, Sunday 1 May 2011. The abstract for this work is reproduced below: see link http://www.endocrineabstracts.org/ea/0026/ea0026p99.htm The 13 European Congress of Endocrinology, Europes biggest scientific meeting on hormones, is taking place in Rotterdam, The Netherlands from 30 April 4 May 2011. For the full programme, see http://www.ece2011.com/.
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Table 2 Prevalence of PCOS The following table gives an indication of approximate numbers of women with PCOS in major countries. These are rounded figures based on the number of women who fall within the reproductive ages 15-44, using an 8% prevalence of PCOS. Country USA (a) Germany (b) France (b) Italy (b) Spain (b) UK (b) Number women aged 15-44 62 million 17.55 million 13.6 million 12.7 million 10.02 million 12.9 million Approx number with PCOS 5 million 1.4 million 1.09 million 1.02 million 800,000 1.03 million

(a) U.S. Bureau of the Census, Table 2: annual estimates of the resident population by sex and selected age groups for the United States: April 1, 2000 to July 1, 2008, http://www.census.gov/popest/national/asrh/NC-EST2008/NC-EST2008-02.xls (b) http://epp.eurostat.ec.europa.eu/cache/ITY_OFFPUB/KS-EH-06-001/EN/KS-EH-06-001-EN.PDF 2005 statistics

ABSTRACT Cardiovascular disease risk markers in women with polycystic ovary syndrome: systematic review and meta-analysis. K Toulis, G Mintziori, D Goulis, E Kintiraki, E Eukarpidis, SA Mouratoglou, A Pavlaki, S Stergianos, M Poulasouhidou, T Tzellos, B Tarlatzis Aristotle University of Thessaloniki, Thessaloniki, Greece Introduction. The relation between polycystic ovary syndrome (PCOS) and cardiovascular disease (CVD) remains unclear. The aim of the study was to systematically review the relevant trials that have studied CVD risk factors in woman with PCOS [CRP, Hcy, TNF-, PAI-1, Lp(a), AGEs, VEGF, IL-6, ADMA and fibrinogen] and to meta-analyze the best evidence available. Patients and Methods. Search was conducted in the MEDLINE, EMBASE and CENTRAL d (last update June 2010). Eligible for the systematic reviews were studies, which reported on CVD risk markers levels in women with PCOS compared to controls. Weighted Mean Differences (WMD) and 95% Confidence

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Intervals (CI) were calculated in each of the CVD risk markers for all eligible studies and combined using random effects model. To ensure synthesis of the best available evidence, sensitivity analyses were performed. Results. 130 studies were including in 11 different meta-analyses, involving in total 6260 women with PCOS and 4546 controls. Women with PCOS demonstrated significantly elevated CRP [WMD (95% CI) = 0.96 (0.74 to 1.19)], Hcy [2.25 (1.46 to 3.03)], PAI-1 antigen [16.96 (7.65 to 26.28)], PAI-1 activity [0.70 (0.17 to 1.23)], VEGF [1.72 (0.96 to 2.48)], ADMA [0.19 (0.08 to 0.3)] and AGEs [3.91 (2.36 to 5.45)] levels as compared to controls, yet with significant between-study heterogeneity. Borderline significance was detected for TNF- [0.75 (0.07 to 1.44)] and fibrinogen [0.20 (0.01 to 0.39)] whereas no significance was detected for IL-6 [0.71 (-0.16 to 1.59)]. Conclusions. Women with PCOS have increased serum concentrations of CVD risk factors as compared to controls. If this apparent risk is translated into increased incidence of CVD in later life remains to be elucidated.

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