This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Legro, R. S. Search for Related Content PubMed PubMed Citation Articles by Legro, R. S.

Polycystic Ovary Syndrome and Cardiovascular Disease: A Premature Association?

Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

Correspondence: Address all correspondence and requests for reprints to: Richard S. Legro, M.D., Department of Obstetrics and Gynecology, P.O. Box 850, 500 University Drive, M.S. Hershey Medical Center, Hershey, Pennsylvania 17033. E-mail: rsl1{at}psu.edu

Women with polycystic ovary syndrome (PCOS) are often assumed, a priori, to be at increased risk for cardiovascular disease (CVD), given the high prevalence of the metabolic syndrome X among them. There is, however, no single definition of PCOS, and for that reason a comparison of studies that have analyzed its association with CVD is compromised from the start. Long-term studies of well characterized women with PCOS are lacking, and the link to primary cardiovascular events such as stroke or myocardial infarction remains more speculative than substantive. Epidemiological studies that have focused on isolated signs and stigmata of PCOS, such as polycystic ovaries, hyperandrogenism, or chronic anovulation, have found mixed results. There are studies that suggest a slight increase in cardiovascular events in women with polycystic ovaries, with perhaps stronger evidence between an increased risk of cardiovascular events in women with menstrual irregularity. However, there is little evidence for an association between hyperandrogenism per se and cardiovascular events. Furthermore, there are less data to substantiate an increased risk of events in women with PCOS identified on the basis of a combination of signs and symptoms, such as hyperandrogenic chronic anovulation. The existing data suggest that PCOS may adversely affect or accelerate the development of an adverse cardiovascular risk profile, and even of subclinical signs of atherosclerosis, but it does not appear to lower the age of clinical presentation to a premenopausal age group. Future studies to identify the risk of cardiovascular events in women with PCOS will benefit from clear and extensive phenotyping of PCOS abnormalities at baseline, from a prospective design, from larger sample sizes, and from longer follow-up.

This article has been cited by other articles:

				M. Rizzo, K. Berneis, M. Hersberger, I. Pepe, G. Di Fede, G. B. Rini, G. A. Spinas, and E. Carmina Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype Hum. Reprod., May 19, 2009; (2009) dep121v1. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, C. Mendieta-Azcona, J. M del Rey Sanchez, M. Maties, and H. F Escobar-Morreale Effects of an antiandrogenic oral contraceptive pill compared with metformin on blood coagulation tests and endothelial function in women with the polycystic ovary syndrome: influence of obesity and smoking Eur. J. Endocrinol., March 1, 2009; 160(3): 469 - 480. [Abstract] [Full Text] [PDF]

				I. J. G. Ketel, C. D. A. Stehouwer, E. H. Serne, T. J. M. Korsen, P. G. A. Hompes, Y. M. Smulders, R. T. de Jongh, R. Homburg, and C. B. Lambalk Obese But Not Normal-Weight Women with Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3365 - 3372. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, F. Alvarez-Blasco, M. G. Uriol Rivera, and H. F. Escobar-Morreale Serum uric acid concentration as non-classic cardiovascular risk factor in women with polycystic ovary syndrome: effect of treatment with ethinyl-estradiol plus cyproterone acetate versus metformin Hum. Reprod., July 1, 2008; 23(7): 1594 - 1601. [Abstract] [Full Text] [PDF]

				L. J. Shaw, C. N. Bairey Merz, R. Azziz, F. Z. Stanczyk, G. Sopko, G. D. Braunstein, S. F. Kelsey, K. E. Kip, R. M. Cooper-DeHoff, B. D. Johnson, et al. Postmenopausal Women with a History of Irregular Menses and Elevated Androgen Measurements at High Risk for Worsening Cardiovascular Event-Free Survival: Results from the National Institutes of Health--National Heart, Lung, and Blood Institute Sponsored Women's Ischemia Syndrome Evaluation J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1276 - 1284. [Abstract] [Full Text] [PDF]

				N. Zhang, Y.-H. Shi, C.-F. Hao, H. F Gu, Y. Li, Y.-R. Zhao, L.-C. Wang, and Z.-J. Chen Association of +45G15G(T/G) and +276(G/T) polymorphisms in the ADIPOQ gene with polycystic ovary syndrome among Han Chinese women Eur. J. Endocrinol., February 1, 2008; 158(2): 255 - 260. [Abstract] [Full Text] [PDF]

				B. O. Yildiz, E. S. Knochenhauer, and R. Azziz Impact of Obesity on the Risk for Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 162 - 168. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, C. Mendieta-Azcona, F. Alvarez-Blasco, and H. F. Escobar-Morreale Androgen excess is associated with the increased carotid intima-media thickness observed in young women with polycystic ovary syndrome Hum. Reprod., December 1, 2007; 22(12): 3197 - 3203. [Abstract] [Full Text] [PDF]

				V. Skov, D. Glintborg, S. Knudsen, T. Jensen, T. A. Kruse, Q. Tan, K. Brusgaard, H. Beck-Nielsen, and K. Hojlund Reduced Expression of Nuclear-Encoded Genes Involved in Mitochondrial Oxidative Metabolism in Skeletal Muscle of Insulin-Resistant Women With Polycystic Ovary Syndrome Diabetes, September 1, 2007; 56(9): 2349 - 2355. [Abstract] [Full Text] [PDF]

				X. Ma, L. Fan, Y. Meng, Z. Hou, Y.-D. Mao, W. Wang, W. Ding, and J.-Y. Liu Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome Mol. Hum. Reprod., August 1, 2007; 13(8): 527 - 535. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, F. Alvarez-Blasco, J. I. Botella-Carretero, E. Martinez-Bermejo, M. A. Lasuncion, and H. F. Escobar-Morreale Comparison of Ethinyl-Estradiol Plus Cyproterone Acetate Versus Metformin Effects on Classic Metabolic Cardiovascular Risk Factors in Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2453 - 2461. [Abstract] [Full Text] [PDF]

				M. Luque-Ramirez, F. Alvarez-Blasco, C. Mendieta-Azcona, J. I. Botella-Carretero, and H. F. Escobar-Morreale Obesity Is the Major Determinant of the Abnormalities in Blood Pressure Found in Young Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2141 - 2148. [Abstract] [Full Text] [PDF]

				M.-J. Chen, W.-S. Yang, J.-H. Yang, C.-L. Chen, H.-N. Ho, and Y.-S. Yang Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome Hypertension, June 1, 2007; 49(6): 1442 - 1447. [Abstract] [Full Text] [PDF]

				J. A. Beckman, A. B. Goldfine, A. Dunaif, M. Gerhard-Herman, and M. A. Creager Endothelial Function Varies According to Insulin Resistance Disease Type Diabetes Care, May 1, 2007; 30(5): 1226 - 1232. [Abstract] [Full Text] [PDF]

				R. S. Legro A 27-Year-Old Woman With a Diagnosis of Polycystic Ovary Syndrome JAMA, February 7, 2007; 297(5): 509 - 519. [Abstract] [Full Text] [PDF]

				J. L. San Millan, F. Alvarez-Blasco, M. Luque-Ramirez, J. I. Botella-Carretero, and H. F. Escobar-Morreale The PON1-108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women Hum. Reprod., December 1, 2006; 21(12): 3157 - 3161. [Abstract] [Full Text] [PDF]

				The ESHRE Capri Workshop Group Hormones and cardiovascular health in women Hum. Reprod. Update, September 1, 2006; 12(5): 483 - 497. [Abstract] [Full Text] [PDF]

				S. Eisenhardt, N. Schwarzmann, V. Henschel, A. Germeyer, M. von Wolff, A. Hamann, and T. Strowitzki Early Effects of Metformin in Women with Polycystic Ovary Syndrome: A Prospective Randomized, Double-Blind, Placebo-Controlled Trial J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 946 - 952. [Abstract] [Full Text] [PDF]

				M. E. Zanolin, F. Tosi, G. Zoppini, R. Castello, G. Spiazzi, R. Dorizzi, M. Muggeo, and P. Moghetti Clustering of Cardiovascular Risk Factors Associated With the Insulin Resistance Syndrome: Assessment by principal component analysis in young hyperandrogenic women Diabetes Care, February 1, 2006; 29(2): 372 - 378. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann, D. R. Liljenquist, K. Kasza, R. Azziz, R. S. Legro, M. N. Ghazzi, and for the PCOS/Troglitazone Study Group Prevalence and Predictors of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 48 - 53. [Abstract] [Full Text] [PDF]

				H. F. Escobar-Morreale, J. I. Botella-Carretero, F. Alvarez-Blasco, J. Sancho, and J. L. San Millan The Polycystic Ovary Syndrome Associated with Morbid Obesity May Resolve after Weight Loss Induced by Bariatric Surgery J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6364 - 6369. [Abstract] [Full Text] [PDF]

				M. Yilmaz, N. Bukan, G. Ayvaz, A. Karakoc, F. Toruner, N. Cakir, and M. Arslan The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome Hum. Reprod., December 1, 2005; 20(12): 3333 - 3340. [Abstract] [Full Text] [PDF]

				M. Kravariti, K. K. Naka, S. N. Kalantaridou, N. Kazakos, C. S. Katsouras, A. Makrigiannakis, E. A. Paraskevaidis, G. P. Chrousos, A. Tsatsoulis, and L. K. Michalis Predictors of Endothelial Dysfunction in Young Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5088 - 5095. [Abstract] [Full Text] [PDF]

				M. Yilmaz, N. Bukan, R. Ersoy, A. Karakoc, I. Yetkin, G. Ayvaz, N. Cakir, and M. Arslan Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome Hum. Reprod., September 1, 2005; 20(9): 2414 - 2420. [Abstract] [Full Text] [PDF]

				R. Azziz, C. Marin, L. Hoq, E. Badamgarav, and P. Song Health Care-Related Economic Burden of the Polycystic Ovary Syndrome during the Reproductive Life Span J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4650 - 4658. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Second World Congress on the Insulin Resistance Syndrome: Mediators, pediatric insulin resistance, the polycystic ovary syndrome, and malignancy Diabetes Care, July 1, 2005; 28(7): 1821 - 1830. [Full Text] [PDF]

				M.A. Checa, A. Requena, C. Salvador, R. Tur, J. Callejo, J.J. Espinos, F. Fabregues, J. Herrero, and (Reproductive Endocrinology Interest Group of the Insulin-sensitizing agents: use in pregnancy and as therapy in polycystic ovary syndrome Hum. Reprod. Update, July 1, 2005; 11(4): 375 - 390. [Abstract] [Full Text] [PDF]

				E. Carmina, M. C. C. R. A. Longo, G. B. Rini, and R. A. Lobo Phenotypic Variation in Hyperandrogenic Women Influences the Findings of Abnormal Metabolic and Cardiovascular Risk Parameters J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2545 - 2549. [Abstract] [Full Text] [PDF]

				A. Vryonidou, A. Papatheodorou, A. Tavridou, T. Terzi, V. Loi, I.-A. Vatalas, N. Batakis, C. Phenekos, and A. Dionyssiou-Asteriou Association of Hyperandrogenemic and Metabolic Phenotype with Carotid Intima-Media Thickness in Young Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2740 - 2746. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann Polycystic Ovary Syndrome N. Engl. J. Med., March 24, 2005; 352(12): 1223 - 1236. [Full Text] [PDF]

				C. Ortega-Gonzalez, S. Luna, L. Hernandez, G. Crespo, P. Aguayo, G. Arteaga-Troncoso, and A. Parra Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1360 - 1365. [Abstract] [Full Text] [PDF]

				D. A. Ehrmann, K. Kasza, R. Azziz, R. S. Legro, M. N. Ghazzi, and for the PCOS/Troglitazone Study Group Effects of Race and Family History of Type 2 Diabetes on Metabolic Status of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 66 - 71. [Abstract] [Full Text] [PDF]

				G. A. R. Maciel, E. C. Baracat, J. A. Benda, S. M. Markham, K. Hensinger, R. J. Chang, and G. F. Erickson Stockpiling of Transitional and Classic Primary Follicles in Ovaries of Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5321 - 5327. [Abstract] [Full Text] [PDF]

				F. Orio Jr., S. Palomba, L. Spinelli, T. Cascella, L. Tauchmanova, F. Zullo, G. Lombardi, and A. Colao The Cardiovascular Risk of Young Women with Polycystic Ovary Syndrome: An Observational, Analytical, Prospective Case-Control Study J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3696 - 3701. [Abstract] [Full Text] [PDF]

				R. S. Legro, E. Myers, and for the Reproductive Medicine Network Surrogate end-points or primary outcomes in clinical trials in women with polycystic ovary syndrome? Hum. Reprod., August 1, 2004; 19(8): 1697 - 1704. [Abstract] [Full Text] [PDF]

				R. Azziz, K. S. Woods, R. Reyna, T. J. Key, E. S. Knochenhauer, and B. O. Yildiz The Prevalence and Features of the Polycystic Ovary Syndrome in an Unselected Population J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2745 - 2749. [Abstract] [Full Text] [PDF]

				S. Taponen, H. Martikainen, M.-R. Jarvelin, U. Sovio, J. Laitinen, A. Pouta, A.-L. Hartikainen, M. I. McCarthy, S. Franks, M. Paldanius, et al. Metabolic Cardiovascular Disease Risk Factors in Women with Self-Reported Symptoms of Oligomenorrhea and/or Hirsutism: Northern Finland Birth Cohort 1966 Study J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2114 - 2118. [Abstract] [Full Text] [PDF]

				N. Boulman, Y. Levy, R. Leiba, S. Shachar, R. Linn, O. Zinder, and Z. Blumenfeld Increased C-Reactive Protein Levels in the Polycystic Ovary Syndrome: A Marker of Cardiovascular Disease J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2160 - 2165. [Abstract] [Full Text] [PDF]

				R. J. Norman, M. Noakes, R. Wu, M. J. Davies, L. Moran, and J. X. Wang Improving reproductive performance in overweight/obese women with effective weight management Hum. Reprod. Update, May 1, 2004; 10(3): 267 - 280. [Abstract] [Full Text] [PDF]

				M. Littleton-Kearney and P. D. Hurn Testosterone as a Modulator of Vascular Behavior Biol Res Nurs, April 1, 2004; 5(4): 276 - 285. [Abstract] [PDF]

				H. F. Escobar-Morreale, J. I. Botella-Carretero, G. Villuendas, J. Sancho, and J. L. San Millan Serum Interleukin-18 Concentrations Are Increased in the Polycystic Ovary Syndrome: Relationship to Insulin Resistance and to Obesity J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 806 - 811. [Abstract] [Full Text] [PDF]

				The Rotterdam ESHRE/ASRM-sponsored PCOS consensus Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) Hum. Reprod., January 1, 2004; 19(1): 41 - 47. [Abstract] [Full Text] [PDF]

				S. Elsenbruch, S. Hahn, D. Kowalsky, A. H. Offner, M. Schedlowski, K. Mann, and O. E. Janssen Quality of Life, Psychosocial Well-Being, and Sexual Satisfaction in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5801 - 5807. [Abstract] [Full Text] [PDF]

				R. S. Legro, R. Azziz, D. Ehrmann, A. G. Fereshetian, M. O'Keefe, and M. N. Ghazzi Minimal Response of Circulating Lipids in Women with Polycystic Ovary Syndrome to Improvement in Insulin Sensitivity with Troglitazone J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5137 - 5144. [Abstract] [Full Text] [PDF]

				J. L. Sharpless Polycystic Ovary Syndrome and the Metabolic Syndrome Clin. Diabetes, October 1, 2003; 21(4): 154 - 161. [Abstract] [Full Text] [PDF]