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Diabetes Care 28:1201-1203, 2005
© 2005 by the American Diabetes Association, Inc.

Clinical Care/Education/Nutrition
Brief Report

High Proportions of Erectile Dysfunction in Men With the Metabolic Syndrome

Katherine Esposito, MD1, Francesco Giugliano, MD2, Emilia Martedì, MD1, Giovanni Feola, MD1, Raffaele Marfella, MD, PHD1, Massimo D’Armiento, MD2 and Dario Giugliano, MD, PHD1

1 Division of Metabolic Diseases, Second University of Naples, Naples, Italy
2 Division of Urology, Second University of Naples, Naples, Italy

Address correspondence and reprint requests to Katherine Esposito, MD, Division of Metabolic Diseases, Second University of Naples, Piazza L. Miraglia, 80138 Naples, Italy. E-mail: katherine.esposito{at}unina2.it

Abbreviations: CRP, C-reactive protein • IIEF, International Index of Erectile Function


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
Erectile dysfunction is an important cause of decreased quality of life in men (1,2). Strong epidemiological evidence links the subsequent risk of erectile dysfunction to the presence of well-recognized risk factors for coronary heart disease, such as increased body weight, hypertension, and dyslipidemia (3,4). Some have suggested that a diagnosis of erectile dysfunction is a sentinel event that should prompt investigation for coronary heart disease in asymptomatic men (5). We postulated an association between erectile dysfunction and the metabolic syndrome because four of the five components of the metabolic syndrome are risk factors for erectile dysfunction and are also characterized by abnormal endothelial function (6).


   RESEARCH DESIGN AND METHODS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
Men were recruited among those attending the outpatient department for metabolic diseases of the teaching hospital at the second University of Naples, Naples, Italy. To be enrolled in the study, subjects had to have three or more of the criteria to meet the diagnosis of the metabolic syndrome, as recommended by the Adult Treatment Panel (7). Exclusion criteria were diabetes or impaired glucose tolerance, impaired renal function, pelvic trauma, prostatic disease, peripheral or autonomic neuropathy, hypertension (blood pressure >140/90 mmHg), cardiovascular disease, psychiatric problems, use of drugs or alcohol abuse, and smoking (both present and past smoking). Endocrine causes of erectile dysfunction were also excluded. A total of 50 men, matched for age and body weight, served as the control group. The study was approved by the institutional committee of ethical practice of our institution, and all of the study subjects gave written informed consent.

Erectile function was assessed by completing questions one through five of the International Index of Erectile Function (IIEF), which is a multidimensional questionnaire for assessing erectile dysfunction (8). The erectile function score represents the sum of questions one through five of the IIEF questionnaire, with a maximum score of 25; a score ≤21 indicates erectile dysfunction.

Endothelial function was assessed with the L-arginine test, as previously described (9). We developed a score in which the blood pressure and platelet aggregation responses to L-Arginine (3 g i.v.) were summed. This gives a score ranging from 0 points, indicating maximal impairment of endothelial function, to 10 points, indicating normal function of the endothelium (10).

Assays for serum total and HDL cholesterol, triglyceride, and glucose levels were performed in the hospital’s chemistry laboratory. High-sensitivity C-reactive protein (CRP) was assayed by immunonephelometry on a Behring Nephelometer 2 (Dade Behring, Marburg, Germany).

Data are presented as the mean ± SD unless otherwise indicated. We compared baseline data using a t test for continuous variables and Wilcoxon’s test for CRP. We classified all study patients as having three, four, or five components of the metabolic syndrome and assessed for evidence of a relationship among erectile dysfunction, median CRP level, and endothelial function score across these groups using the Jonckheere-Terpstra test. The {chi}2 test was used for comparing proportions of subjects with erectile dysfunction. Spearman’s rank correlation coefficients were used to quantify the relationship among IIEF score, endothelial function score, and CRP level. All analyses were conducted using SPSS version 9.0 (SPSS, Chicago, IL).


   RESULTS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
Men with the metabolic syndrome (n = 100) were matched with men of the control group for age (38.4 ± 3.3 vs. 37.9 ± 2.9 years) and BMI (26.9 ± 1.9 vs. 26.6 ± 2.1 kg/m2). Compared with the control group, patients with the metabolic syndrome had an increased prevalence of erectile dysfunction (26.7 vs. 13%, P = 0.03), reduced endothelial function score (6.3 ± 0.9 vs. 9.5 ± 0.3, P = 0.01), and higher circulating concentrations of CRP (median [interquartile range] 1.7 [0.6–3.8] vs. 0.6 [0.2–2.7] mg/l).

Erectile dysfunction prevalence (IIEF <21) and CRP level increased as the number of components of the metabolic syndrome increased (Fig. 1); by contrast, there was an inverse relationship between the number of components of the metabolic syndrome and the endothelial function score (P for trend <0.01).



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  		Figure 1— Distribution of erectile dysfunction (IIEF <21), endothelial function score, and CRP level among patients by the presence of three, four, and five components of the metabolic syndrome.

 
The IIEF score was positively associated with the endothelial function score (r = 0.24, P = 0.04) and negatively associated with CRP (r = 0.27, P = 0.03). These correlations were little affected by adjustment for age.


   CONCLUSIONS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
Erectile dysfunction is present in up to 30 million men in the U.S. and ~100 million men worldwide (11) and affects up to 52% of men between the ages of 40 and 70 years (2). Our results show a linear increment in the prevalence of erectile dysfunction that is associated with a linear increase in CRP level and a linear impairment of endothelial function score as the number of components of the metabolic syndrome increased. Moreover, the association we found between IEEF and endothelial function score supports the presence of some common vascular pathways underlying both conditions. A defective nitric oxide (NO) activity, linked to reduced NO availability, could provide a unifying explanation for this association. In particular, in isolated corpus cavernosum strips from patients with erectile dysfunction, both neurogenic- and endothelium-dependent relaxation are impaired (12). Moreover, erectile dysfunction in diabetic men correlates with endothelial dysfunction and endothelial activation (13). Lastly, CRP, at concentrations known to predict diverse vascular insults, profoundly quenches NO synthesis, while augmenting the release of endothelin-1 and upregulating adhesion molecules and chemoattractant chemokines, uncovering a proinflammatory and proatherosclerotic phenotype (14). Interestingly enough, Kaiser et al. (15) recently reported that subjects with erectile dysfunction but without evidence of clinical cardiovascular disease and free of traditional cardiovascular risk factors present widespread abnormality of endothelial function, as has been seen in patients with cardiovascular risk factors (7). Thus, many patients with erectile dysfunction seem to have a vascular mechanism similar to that seen in atherosclerosis.

The metabolic syndrome is highly prevalent in the U.S. population (16). Thus, a large group of people are at increased risk for developing diabetes and cardiovascular disease. Although the greater prevalence of erectile dysfunction in men with the metabolic syndrome needs to be confirmed in larger epidemiological studies, the linear relationship we found between the number of components of the syndrome and erectile dysfunction is suggestive for a progressive burden of raising cardiovascular risk on erectile function. In any case, the adoption of a healthy lifestyle is strongly recommended in order to reduce the prevalence of the metabolic syndrome (10) and hence the burden of erectile dysfunction.


   Footnotes
 
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Received for publication November 10, 2004. Accepted for publication January 20, 2005.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

  1. Litwin MS, Nied RJ, Dhanani N: Health-related quality of life in men with erectile dysfunction. J Gen Intern Med 13:159–166, 1998[Medline]
  2. Laumann EO, Paik A, Rosen RC: Sexual dysfunction in the United States: prevalence and predictors. JAMA 281:537–544, 1999[Abstract/Free Full Text]
  3. Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB, McKinlay JB: Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 30:328–338, 2000[Medline]
  4. Fung MM, Bettencourt R, Barrett-Connor H: Heart disease risk factors predict erectile dysfunction 25 years later. J Am Coll Cardiol 43:1405–1411, 2004[Abstract/Free Full Text]
  5. Blumentals WA, Gomez-Caminero A, Joo S, Vannappagari V: Should erectile dysfunction be considered as a marker for acute myocardial infarction? Int J Impot Res 16:350–353, 2004[Medline]
  6. Calermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE: Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interactions. J Am Coll Cardiol 24:1468–1474, 1994[Abstract]
  7. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497, 2001[Free Full Text]
  8. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A: The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49:822–830, 1997[Medline]
  9. Giugliano D, Marfella R, Verrazzo G, Acampora R, Nappo F, Ziccardi P, Coppola L, D’Onofrio F: L-arginine for testing endothelium-dependent vascular functions in humans. Am J Physiol 273:E606–E612, 1997
  10. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D’Armiento M, D’Andrea F, Giugliano D: Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 292:1440–1446, 2004[Abstract/Free Full Text]
  11. Lue TF: Erectile dysfunction. N Engl J Med 342:1802–1813, 2000[Free Full Text]
  12. Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA: Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med 320:1025–1030, 1989[Abstract]
  13. De Angelis L, Marfella MA, Siniscalchi M, Marino L, Nappo F, Giugliano F, De Lucia D, Giugliano D: Erectile and endothelial dysfunction in type II diabetes: a possibile link. Diabetologia 44:1155–1160, 2001[Medline]
  14. Verma S, Wang CH, Li SH, Dumont AS, Fedak PW, Badiwala MV, Dhillon B, Weisel RD, Li RK, Mickle DA, Stewart DJ: A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 106:913–919, 2002[Abstract/Free Full Text]
  15. Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ: Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction but no other clinical cardiovascular disease. J Am Coll Cardiol 43:179–184, 2004[Abstract/Free Full Text]
  16. Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA 287:356–359, 2002[Abstract/Free Full Text]

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