Erectile Dysfunction as a Predictor of the Metabolic Syndrome in Aging Men: Results From the Massachusetts Male Aging Study Varant Kupelian, Ridwan Shabsigh,* Andre B. Araujo, Amy B. O’Donnell and John B. McKinlay† From the New England Research Institutes, Watertown, Massachusetts (VK, ABA, ABO, JBM), and Department of Urology, Columbia University, New York, New York (RS) Purpose: The metabolic syndrome, characterized by central obesity, insulin dysregulation, abnormal lipids and borderline hypertension, is a precursor state for cardiovascular disease. We determined whether erectile dysfunction is predictive of the metabolic syndrome. Materials and Methods: Data were obtained from the Massachusetts Male Aging Study, a population based prospective cohort observed at 3 points during approximately 15 years (T 1 —1987 to 1989, T 2 —1995 to 1997, T 3 —2002 to 2004). The metabolic syndrome was defined by using a modification of the Adult Treatment Panel III guidelines. The association between erectile dysfunction and the metabolic syndrome was assessed using relative risks and 95% confidence intervals estimated using Poisson regression models. Results: Analysis was conducted of 928 men without the metabolic syndrome at T 1 . There were 293 men with incident metabolic syndrome, of which 56 had erectile dysfunction at baseline. Body mass index and the presence of 1 or 2 conditions constituting the metabolic syndrome definition were the strongest predictors of the metabolic syndrome. The association of erectile dysfunction with the metabolic syndrome (unadjusted RR 1.35, 95% CI 1.01–1.81) was modified by body mass index, with a stronger effect of erectile dysfunction in men with body mass index less than 25 (adjusted RR 2.09, 95% CI 1.09 – 4.02), and no erectile dysfunction and metabolic syndrome association in men with body mass index 25 or greater (adjusted RR 1.06, 95% CI 0.76 –1.50). Conclusions: Erectile dysfunction was predictive of the metabolic syndrome only in men with body mass index less than 25. This finding suggests that erectile dysfunction may provide a warning sign and an opportunity for early intervention in men otherwise considered at lower risk for the metabolic syndrome and subsequent cardiovascular disease. Key Words: impotence, metabolic syndrome X, epidemiology, aging C oronary heart disease and type 2 diabetes are major causes of morbidity and mortality in the United States with prevalence rates of 6.9% and 6.7%, re- spectively, and CHD causing 1 of every 5 deaths. 1 Much irreversible vascular damage has already been done by the time these conditions are diagnosed. It is estimated that DM is diagnosed 4 to 7 years after initial onset 2 and about 50% of CHD deaths occur in undiagnosed cases. 1 The metabolic syndrome, characterized by dyslipidemia, hyperglycemia, hypertension and central obesity, is a precursor state of CHD and DM. The constellation of CHD and DM risk factors that define MetS are thought to be linked by insulin resistance. 3 Apply- ing MetS prevalence rates from the Third National Health and Nutrition Examination Survey to United States census counts from 2000, an estimated 47 million United States residents meet the criteria for MetS. 4 Data from the San Antonio Heart Study, which followed more than 1,700 par- ticipants for 7 to 8 years, show that MetS is predictive of diabetes independently of other factors. 5 Data from the West of Scotland Coronary Prevention Study, which followed ap- proximately 6,000 men during 5 years, found that men with MetS had a 3.7-fold increased risk of CHD events and, more strikingly, a 24.5-fold increased risk of incident diabetes. 6 Identification of a reliable early precursor of MetS would provide an opportunity for the prevention of diabetes and its complications. Risk factors for CHD have been shown to predict ED. 7 ED has also been associated with diabetes, overweight, hypertension, and high total cholesterol and low HDL cholesterol. 7–9 Given these observations it is likely that ED and MetS are also related. Our study moved the focus even further upstream by examining the relationship of ED with the subsequent development of MetS using longitudi- nal data from the MMAS, a large prospective cohort of men followed for more than 15 years. MATERIALS AND METHODS Study Sample The MMAS is a population based prospective observational study of middle-aged men observed at 3 points (T 1 —1987 to 1989, T 2 —1995 to 1997, T 3 —2002 to 2004). The sampling Submitted for publication September 20, 2005. Supported by Grant AG04763 from the National Institute on Ag- ing, and Grants DK51345 and DK44995 from the National Institute of Diabetes and Digestive and Kidney Diseases. * Financial interest and/or other relationship with Pfizer, Lilly Icos, Boehringer Ingelheim, Bayer/GSK/Schering Plough, Solvay, American Medical Systems, Schering AG and Johnson & Johnson. † Correspondence: New England Research Institutes, 9 Galen St., Watertown, Massachusetts 02472 (telephone: 617-923-7747 ext. 512; FAX: 617-924-0968; e-mail: jmckinlay@neriscience.com). See Editorial on page 10. 0022-5347/06/1761-0222/0 Vol. 176, 222-226, July 2006 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2006 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/S0022-5347(06)00503-9 222