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Preliminary report of association of chronic diseases and erectile dysfunction in middle-aged men in Japan
ADULT UROLOGY
PRELIMINARY REPORT OF ASSOCIATION OF CHRONIC DISEASES AND ERECTILE DYSFUNCTION IN MIDDLE-AGED MEN IN JAPAN YOSHIO NAYA, YOICHI MIZUTANI, ATSUSHI OCHIAI, JINTETSU SOH, AKIHIRO KAWAUCHI, AKIRA FUJITO, NAOTO NAKAMURA, TOSHIHIKO ONO, NORIYUKI IWAMOTO, TADASHI AOKI, KEN MARUMO, MASARU MURAI, AND TSUNEHARU MIKI
ABSTRACT Objectives. To investigate the effect of chronic diseases on erectile dysfunction (ED) in Japanese middleaged men using the International Index of Erectile Function, 5-item version (IIEF-5). Methods. The subjects consisted of 640 healthy men and 396 men with chronic disease who responded to the IIEF-5 questionnaire (mean age 43.6 ⫾ 8.3 years, range 30 to 59). The incidence and severity of ED were calculated in three age groups (30 to 39, 40 to 49, and 50 to 59 years). Results. The incidence of hypertension, cardiac disease, diabetes mellitus, and chronic renal failure was associated with the incidence and severity of ED, as was age. In stepwise multivariate logistic regression analysis, cardiac disease was the strongest independent risk factor (odds ratio [OR] 6.5), followed by diabetes mellitus (OR 5.9), chronic renal failure (OR 3.9), hypertension (OR 2.0), and age (OR 1.8). Conclusions. The results of this study demonstrated that the risk of ED increases with the presence of cardiac disease, diabetes mellitus, chronic renal failure, and hypertension in middle-aged men in Japan. UROLOGY 62: 532–536, 2003. © 2003 Elsevier Inc.
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t is well known that aging and chronic diseases such as diabetes mellitus, chronic renal failure (CRF), hepatic failure, and vascular disease are associated with erectile dysfunction (ED).1–3 ED is a severe problem for middle-aged men that negatively affects their quality of life. Although previous studies have shown the relationships between ED and chronic diseases, as well as between ED and age,1–15 a limited number of investigations have described the association of ED with a variety of independent risk factors.2,6,16 In addition, different methods were used for the evaluation of ED in each study. Furthermore, the internationally esFrom the Department of Urology, Kyoto Prefectural University of Medicine; Department of Urology, Rakuwakai-Marutamachi Hospital; First Department of Internal Medicine, Kyoto Prefectural University of Medicine; Department of Urology, Toujinkai Hospital; Department of Urology, Kyoto First Red-Cross Hospital; Department of Urology, Nishijin Hospital, Kyoto; and Department of Urology, Keio University School of Medicine, Tokyo, Japan Reprint requests: Yoichi Mizutani, M.D., Department of Urology, Kyoto Prefectural University of Medicine, KawaramachiHirokoji, Kyoto 602-8566, Japan Submitted: January 30, 2003, accepted (with revisions): March 27, 2003
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© 2003 ELSEVIER INC. ALL RIGHTS RESERVED
tablished scales should be used for the assessment of ED. Rosen et al.17 reported on the International Index of Erectile Function (IIEF), which has been shown to be a cross-culturally and psychometrically valid measure of ED. It has high sensitivity and specificity for evaluating the effects of treatment in patients with ED of broad-spectrum etiology. An abridged 5-item version of the IIEF (IIEF-5) has been created from the 15-item IIEF.18 It is a brief, reliable, and valid self-administered questionnaire of five items and is favorable for determining the presence and severity of ED. ED is a greater problem for middle-aged men than for elderly men. We assessed the erectile function in Japanese middleaged men with chronic disease and compared each disease as a risk factor for ED using the IIEF-5. MATERIAL AND METHODS The subjects comprised 1036 Japanese male residents of Tokyo, Kyoto, and Osaka who responded to the IIEF-5 questionnaire and a survey on health status (age, present illnesses, and previous history of medication, hospitalization, and surgery) between December 1997 and September 1999 (response rate 65.6%). The questionnaires were self-administered at 0090-4295/03/$30.00 doi:10.1016/S0090-4295(03)00383-2
TABLE I. Characteristics of 1036 men Age (yr) Group Control (n ⫽ 640) Chronic disease* (n ⫽ 396) Each disease Hypertension (n ⫽ 84) Cardiac disease (n ⫽ 17) Hyperlipidemia (n ⫽ 34) Hyperuricemia (n ⫽ 17) Diabetes mellitus (n ⫽ 47) Peptic ulcer (n ⫽ 59) Allergic disease (n ⫽ 24) Chronic renal failure (n ⫽ 35) Disc hernia (n ⫽ 12) Others (n ⫽ 135)
41.4 ⫾ 8.0 47.2 ⫾ 7.3† 51.4 51.4 46.4 46.9 51.5 45.4 48.4 49.5 45.2 46.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
4.4† 8.5† 7.6† 7.4 6.5† 10.9† 6.8† 8.4† 8.8† 7.1†
IIEF-5 Score 19.4 ⫾ 6.9 17.1 ⫾ 8.1‡ 15.4 8.5 14.0 18.7 11.8 16.8 21.0 12.9 16.3 19.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
8.7‡ 7.7‡ 9.2‡ 8.2 8.3‡ 8.3§ 6.6㛳 8.2‡ 9.2 6.3
Data presented as the mean ⫾ standard deviation. * Of the 396 patients, 68 had duplicate disease. † Mann-Whitney U test, vs. control significantly greater, P ⬍0.0005. ‡ Mann-Whitney U test, vs. control significantly less, P ⬍0.0005. § Mann-Whitney U test, vs. control significantly less, P ⬍0.05. 㛳 Mann-Whitney U test, vs. control significantly greater, P ⬍0.05.
home, and no attempt was made to validate the responders’ answers. Subject age ranged from 30 to 59 years. They consisted of 640 healthy controls and 396 men with chronic disease. The 640 healthy controls were employees of 10 pharmaceutical companies who responded to the questionnaires completely and had no history of present or previous illness. The 396 men with chronic disease were patients who had visited the clinics of five institutions (Kyoto Prefectural University of Medicine, Kyoto Miniren-Chuo Hospital, Toujinkai Hospital, Rakuwakai-Marutamachi Hospital, and RakuwakaiOtowa Hospital). Table I shows the characteristics of the 1036 men. The mean age of the patients with chronic disease was significantly greater than that of the healthy controls (P ⬍0.0001). The mean IIEF-5 score of those with chronic disease was significantly lower than that of the healthy controls (P ⬍0.0001). Thirty-four patients with CRF undergoing hemodialysis did not have diabetes. Other diseases consisted of otorhinolaryngologic diseases (n ⫽ 15), chronic dermatitis (n ⫽ 11), hemorrhoids (n ⫽ 11), orthopedic diseases (n ⫽ 11), urolithiasis (n ⫽ 11), respiratory infection (n ⫽ 10), cerebral infarction (n ⫽ 6), chronic gastritis (n ⫽ 6), urinary tract infection (n ⫽ 6), chronic hepatitis (n ⫽ 5), dental diseases (n ⫽ 5), asthma (n ⫽ 4), chronic nephritis (n ⫽ 4), chronic prostatitis (n ⫽ 4), gall bladder stone (n ⫽ 4), ophthalmologic diseases (n ⫽ 4), colitis (n ⫽ 3), angiitis (n ⫽ 2), chronic pancreatitis (n ⫽ 2), colon polyp (n ⫽ 2), herpes zoster (n ⫽ 2), hyperthyroidism (n ⫽ 2), inguinal hernia (n ⫽ 2), benign prostatic hyperplasia (n ⫽ 1), rheumatoid arthritis (n ⫽ 1), and ulcerative colitis (n ⫽ 1). We used the Japanese version of the IIEF-5, as previously described.5 The IIEF-5 questionnaire was self-administered in the subjects’ homes. ED was diagnosed when the IIEF-5 score was less than 22.18 We evaluated the incidence of ED by the IIEF-5 score in each age group (30 to 39, 40 to 49, and 50 to 59 years). The ED severity was classified into five categories in each age group: no ED, IIEF-5 score 22 to 25; mild ED, IIEF-5 score 17 to 21; mild-to-moderate ED, IIEF-5 score 12 to 16; moderate ED, IIEF-5 score 8 to 11; and severe ED, IIEF-5 score 1 to 7.18 The incidence and severity were compared between patients with chronic disease and healthy controls using the MannWhitney U test and one-way analysis of variance (ANOVA). UROLOGY 62 (3), 2003
Log likelihood stepwise multivariate logistic regression analysis was performed on the incidence of ED regarding age and each chronic disease. All statistical analyses were performed using Statistical Package for Social Sciences, version 10 (SPSS, Chicago, Ill). Statistical significance was set at P ⬍0.05 in all analyses.
RESULTS The incidence of ED in controls and those with chronic disease in each age group is shown Table II. By one-way ANOVA, the ED incidence was associated with age (F ⫽ 37.7, P ⬍0.0001), diabetes (F ⫽ 30.9, P ⬍0.0001), hypertension (F ⫽ 22.7, P ⬍0.0001), CRF (F ⫽ 21.5, P ⬍0.0001), cardiac disease (F ⫽ 15.1, P ⬍0.0001), and hyperlipidemia (F ⫽ 7.3, P ⫽ 0.007). The ED incidence in patients with chronic diseases at 50 to 59 years was significantly greater than that in patients at 30 to 39 years (P ⬍0.0001). The ED incidence in patients with hypertension or CRF was significantly greater than that in controls older than 40 years (P ⬍0.05). The ED incidence in patients with cardiac disease or diabetes was significantly greater than that in controls older than 50 years (P ⬍0.005). The ED severity in controls and patients with each chronic disease is shown in Table III. By oneway ANOVA analysis, the severity of ED was associated with age (F ⫽ 18.3, P ⬍0.0001), diabetes (F ⫽ 11.9, P ⬍0.0001), cardiac disease (F ⫽ 8.8, P ⬍0.0001), CRF (F ⫽ 6.9, P ⬍0.0001), hypertension (F ⫽ 5.9, P ⬍0.0001), and hyperlipidemia (F ⫽ 4.0, P ⫽ 0.003). In patients with hypertension, the prevalence of mild and severe ED was significantly greater (P ⬍0.05 and P ⬍0.005, respectively) than in controls. In patients with CRF, 533
TABLE II. Incidence of ED 30–39 yr Control Chronic disease* Hypertension* Cardiac disease* Hyperlipidemia㛳 Diabetes mellitus* Hyperuricemia Peptic ulcer Allergic disease Chronic renal failure* Disc hernia Others
33.0 39.7 25.0 66.7 83.3 75.0 33.3 18.2 18.2 57.1 33.3 38.5
40–49 yr
(101/306) (29/73) (1/4) (2/3) (5/6) (3/4) (1/3) (2/11) (2/11) (4/7) (1/3) (10/26)
37.0 43.5 66.7 100.0 57.1 64.7 12.5 40.0 0 78.6 40.0 29.0
50–59 yr
(77/208) (64/147) (20/30)‡ (2/2) (8/14) (11/17) (1/8) (6/15) (0/6) (11/14)‡ (2/5) (18/62)
42.1 64.8 70.0 91.7 64.3 92.3 66.7 60.6 42.9 92.9 75.0 46.8
Total
(53/126) (114/176)† (35/50)§ (11/12)§ (9/14) (24/26)§ (4/6) (20/33) (3/7) (13/14)§ (3/4) (22/47)
36.1 52.3 66.7 88.2 64.7 80.9 35.3 47.5 20.8 80.0 50.0 37.0
(231/640) (207/396)† (56/84)† (15/17)† (22/34)§ (38/47)† (6/17) (28/59) (5/24) (28/35)† (6/12) (50/135)
KEY: ED ⫽ erectile dysfunction; ANOVA ⫽ analysis of variance. Data presented as the percentage, with the numbers in parentheses. * One-way ANOVA, P ⬍0.0001. † Mann-Whitney U test, vs. control, P ⬍0.0001. ‡ Mann-Whitney U test, vs. control, P ⬍0.05. § Mann-Whitney U test, vs. control, P ⬍0.005. 㛳 One-way ANOVA, P ⫽ 0.007.
TABLE III. Severity of ED in middle-aged men No ED Control Chronic disease* Hypertension* Cardiac disease* Hyperlipidemia¶ Hyperuricemia Diabetes mellitus* Peptic ulcer Allergic disease Chronic renal failure* Disc hernia Others
63.9 47.7 33.7 11.8 35.3 64.7 20.5 52.5 79.2 20.6 50.0 63.2
(409/640) (189/396)† (28/83)† (2/17)† (12/34)# (11/17) (9/44)† (31/59) (19/24) (7/34)† (6/12) (86/136)
Mild to Moderate ED
Mild ED 13.6 19.7 26.5 11.8 11.8 2.1 18.2 11.9 4.2 23.5 16.7 21.3
(87/640) (78/396)‡ (22/83)‡ (2/17) (4/34) (1/17) (8/44) (7/59) (1/24) (8/34)‡ (2/12) (29/136)
Moderate ED
2.8 (18/640) 8.4 (54/640) 3.5 (14/396) 6.3 (25/396) 3.6 (3/83) 9.7 (8/83) 0 11.8 (2/17) 8.8 (3/34) 8.8 (3/34) 2.1 (1/17) 2.1 (1/17) 4.5 (2/44) 11.4 (5/44) 5.1 (3/59) 6.8 (4/59) 0 8.3 (2/24) 11.8 (4/34)‡ 8.8 (3/34) 0 8.3 (1/12) 0.7 (1/136) 2.9 (4/136)**
Severe ED 11.3 22.7 26.5 64.6 35.3 17.6 45.4 23.7 8.3 35.3 25.0 11.8
(72/640) (90/396)§ (22/83)㛳 (11/17)§ (12/34)§ (3/17) (20/44)§ (14/59)㛳 (2/24) (12/34)§ (3/12) (16/136)
Abbreviations as in Table II. Data presented as the percentage, with the number in parentheses. * One-way ANOVA, P ⬍0.0001. † Vs. control, significantly less, P ⬍0.0001. ‡ Vs. control, significantly greater, P ⬍0.05. § Vs. control, significantly greater, P ⬍0.0001. 㛳 Vs. control, significantly greater, P ⬍0.005. ¶ One-way ANOVA, P ⫽ 0.003. # Vs. control, significantly less, P ⬍0.005. ** Vs. control, significantly less, P ⬍0.05.
the prevalence of mild, mild-to-moderate, and severe ED was significantly greater (P ⬍0.05, P ⬍0.05, and P ⬍0.0001, respectively) than in controls. The prevalence of severe ED in those with cardiac disease, diabetes, hyperlipidemia, or peptic ulcer was significantly greater (P ⬍0.0001, P ⬍0.0001, P ⬍0.0001, and P ⬍0.005, respectively) than in controls. The ED severity in patients with cardiac disease was significantly greater than in those with hypertension, hyperlipidemia, peptic ulcer, allergic disease, CRF, disc hernia, and others (P ⬍0.05), but it was equivalent to that in those 534
with diabetes. The ED severity in patients with diabetes was significantly greater than that in those with hypertension, peptic ulcer, allergic disease, and others (P ⬍0.05), but it was equivalent to that in those with CRF and hyperlipidemia. Log likelihood stepwise logistic regression analysis was performed for ED incidence versus each chronic disease or age. Cardiac disease was the strongest risk factor on the basis of its odds ratio (OR) of 6.7 (95% confidence interval [CI] 1.4 to 31.3). Diabetes was the second strongest risk factor (OR 5.9, 95% CI 2.8 to 12.3), followed by CRF (OR UROLOGY 62 (3), 2003
3.9, 95% CI 1.6 to 9.5), hypertension (OR 2.1, 95% CI 1.3 to 3.5), and age older than 50 years (OR 1.8, 95% CI 1.3 to 2.5). Diabetes was the most significant independent risk factor for ED (chi-square 30.0, P ⬍0.0001), followed in order by CRF (chisquare 23.7, P ⬍0.0001), age older than 50 years (chi-square 22.0, P ⬍0.0001), hypertension (chisquare 8.1, P ⫽ 0.005), and cardiac disease (chisquare 7.5, P ⫽ 0.006). We also analyzed the relationship of ED severity with age or chronic disease using stepwise logistic regression analysis. For intermediate ED (IIEF-5 score 16 or less), cardiac disease was the strongest risk factor as determined by its OR of 7.6 (95% CI 2.3 to 24.4). Diabetes was the second strongest risk factor (OR 5.4, 95% CI 2.9 to 10.1), followed by CRF (OR 3.4, 95% CI 1.7 to 7.1), and hyperlipidemia (OR 2.9, 95% CI 1.4 to 6.0). Diabetes was the most significant independent risk factor for ED (chi-square 35.6, P ⬍0.0001), followed in order by cardiac disease (chi-square 25.1, P ⬍0.0001), CRF (chi-square 11.4, P ⫽ 0.001), and hyperlipidemia (chi-square 9.0, P ⫽ 0.003). For severe ED (IIEF-5 score 7 or less), cardiac disease was the strongest risk factor as determined by its OR of 10.2 (95% CI 3.6 to 28.8). Diabetes was the second strongest risk factor (OR 4.1, 95% CI 2.2 to 7.7), followed by age older than 50 years (OR 2.8, 95% CI 1.7 to 4.4), and hyperlipidemia (OR 2.3, 95% CI 1.1 to 5.0). Diabetes was the most significant independent risk factor for ED (chi-square 36.4, P ⬍0.0001), followed in order by cardiac disease (chi-square 36.3, P ⬍0.0001), age older than 50 years (chi-square 11.2, P ⫽ 0.001), and hyperlipidemia (chi-square 4.5, P ⫽ 0.034). COMMENT In the Massachusetts Male Aging Study, the probability of complete ED was 39% in those treated for cardiac disease, 15% in those treated for hypertension, and 28% in those treated for diabetes.6 In the current study, the probability of severe ED was 64.6% in those with cardiac disease, 26.5% in those with hypertension, and 45.4% in those with diabetes. The probability of severe ED in those with cardiac disease, hypertension, or diabetes was greater compared with the results in the Massachusetts Male Aging Study. In the current study, the ED incidence in those with CRF was 79.4%. In previous studies of patients requiring dialysis, 45% to 86% of men had ED.4,7 ED severity was associated with age on the basis of one-way ANOVA analysis. The probability of severe ED in patients with chronic disease at the age of 50 to 59 years was approximately twofold greater than that at age 30 to 39 years. In the Massachusetts Male Aging Study, the probability of complete ED triUROLOGY 62 (3), 2003
pled from 5% to 15% between subject ages of 40 and 70 years.6 In the current study, cardiac disease and hypertension were risk factors for mild ED, moderate ED, and severe ED in multivariate logistic regression analyses. Hyperlipidemia was a risk factor for severe ED and intermediate ED in multivariate logistic regression analysis. These results are consistent with those of previously published studies.9 –13 It is well known that hyperlipidemia is one of the main causes of cardiovascular disease.8 Diabetes is a well-known illness associated with ED.13–15 In the current study, the risk of ED was approximately sixfold greater in diabetic men than in nondiabetic men at middle age, when using a cutoff of 21 for the IIEF-5. In addition, diabetes was a risk factor for severe ED and intermediate ED with an OR of 5.4 and 4.1, respectively. Several studies have reported that the risk of ED in men with diabetes was three to fourfold greater in European countries13,14 and in the United States.6 CRF is also well recognized as an illness that causes ED.4,7 In the current study, CRF was a risk factor for ED in multivariate logistic regression analysis. The risk of ED was approximately four times greater in men undergoing hemodialysis than in men without CRF at middle age when using a cutoff of 21 for the IIEF-5 (mild ED). When using cutoff values of 7 or 16 for the IIEF-5, CRF was not a risk factor for ED. Although diabetes is associated with ED in patients requiring hemodialysis,4,7 we excluded patients with diabetes who required hemodialysis because of age mismatching in the current study. In the current study, the OR of ED for men with diabetes was greater than in several European reports13,14 when using a cutoff of 21 for the IIEF-5. When using a cutoff of 7 for the IIEF-5, the risk of ED for diabetic men was similar to that of previous studies.13,14 The incidence of ED in patients with cardiac disease or diabetes was greater than in several Western reports.6,13,14 These differences may have been due in part to the different method of evaluation for ED used between the previous reports and the current one. In the present study, the incidence of severe ED in men with cardiac disease was greater than that in men with diabetes. Hyperlipidemia was a risk factor for severe ED and intermediate ED, but not for mild ED. Conversely, CRF was a risk factor for mild ED but not for intermediate ED or severe ED. In addition, no association was found with mild to moderate ED and chronic disease, except for CRF. These findings suggest that the severity of ED might be related to the vasculogenic condition and that intermediate ED might be related to endocrinologic and neurogenic conditions. In the current study, we did not evaluate the relationship of ED and smoking. Smoking is a risk 535
factor for ED.19 The prevalence of smoking in Japanese men is 59% and in European and American men is 46% and 35%, respectively.20 Additional study is needed concerning the relationship of ED with smoking and chronic diseases. Many men with a chronic disorder already have ED at middle age according to our results. However, the major limitation of this study was that the data collection was limited to self-report. Medical conditions that may be asymptomatic are often unknown by the subject and consequently underreported. Despite the limitation of the current study, the prevalence of ED and the severity were associated with age, cardiac disease, and diabetes in middle-aged Japanese men. CONCLUSIONS The results of the present study demonstrated that chronic disorders such as cardiac disease, hypertension, diabetes, and CRF are risk factors for ED in Japanese middle-aged men. In particular, cardiac disease was the strongest risk factor for ED, followed by diabetes. The current study was a preliminary study and not a cause-specific or random sample observational study. In addition, the data for the current study were obtained by self-report of the subjects, a major limitation for the evaluation of ED in the current study. Additional studies are needed with well-controlled and large numbers of subjects. Although the current study had some limitations, we should educate young men without chronic disorders, as well as patients with chronic disorders in the early stage, to prevent ED and maintain their quality of life. ACKNOWLEDGMENT. To Drs. M. Maegawa and M. Kondo for assistance in obtaining IIEF questionnaires from male dialysis patients. REFERENCES 1. Marumo K, and Murai M: Epidemiology of erectile dysfunction, in Kim YC, and Tan HM (Eds): APSIR Book on Erectile Dysfunction. Asia-Pacific Society for Impotence Research, 1999, pp 15–26. 2. Marumo K, Nakashima J, and Murai M: Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function. Int J Urol 8: 53–59, 2001. 3. Bortolotti A, Parazzini F, Colli E, et al: The epidemiology of erectile dysfunction and its risk factors. Int J Androl 20: 323–334, 1997.
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4. Naya Y, Soh J, Ochiai A, et al: Significant decrease of the International Index of Erectile Function in male renal failure patients treated with hemodialysis. Int J Impot Res 14: 172– 177, 2002. 5. Naya Y, Soh J, Ochiai A, et al: The erythrocyte aldose reductase is a useful modality for predicting erectile dysfunction in diabetic patients. Int J Impot Res 14: 213–216, 2002. 6. Feldman HA, Goldstein I, Hatzichristou DG, et al: Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151: 54 –61, 1994. 7. Rosas SE, Joffe M, Franklin E, et al: Prevalence and determinants of erectile dysfunction in hemodialysis patients. Kidney Int 59: 2259 –2266, 2001. 8. Kannel WB, McGee D, and Gordon T: A general cardiovascular risk profile: the Framingham Study. Am J Cardiol 38: 46 –51, 1976. 9. Drory Y, Kravetz S, Florian V, et al: Sexual activity after first acute myocardiac infarction in middle-aged men: demographic, psychological and medical predictors. Cardiology 90: 207–211, 1998. 10. Dhabuwara CB, Kumar A, and Pierce JM: Myocardial infarction and its influence on male sexual function. Arch Sex Behav 15: 499 –504, 1986. 11. Solomon H, Man JW, Werzbicki AS, et al: Relation of erectile dysfunction to angiographic coronary artery disease. Am J Cardiol 91: 230 –231, 2003. 12. Kloner RA: Hypertension as a risk for erectile dysfunction: implications for sildenafil use. J Clin Hypertens (Greenwich) 2: 33–36, 2000. 13. Parazzini F, Menchini FF, Bortolotti A, et al: Frequency and determinations of erectile dysfunction in Italy. Eur Urol 37: 43–49, 2000. 14. Martin-Morales A, Sanchez-Cruz JJ, Saenz de Tejada I, et al: Prevalence and independent risk for erectile dysfunction in Spain: results of the Epidemiologia de la Disfunction Erectil Masculina Study. J Urol 166: 569 –574, 2001. 15. Ellenberg M: Sexual function in diabetic patients. Ann Intern Med 92: 331–333, 1980. 16. Nicolosi A, Moreira ED Jr, Shirai M, et al: Epidemiology of erectile dysfunction in four countries: cross-national study of the prevalence and correlates of erectile dysfunction. Urology 61: 201–206, 2003. 17. Rosen RC, Riley A, Wagner G, et al: The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49: 822–830, 1997. 18. Rosen RC, Cappelleri JC, Smith MD, et al: Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res 11: 319 –326, 1999. 19. Mannino DM, Klevens RM, and Flanders WD: Cigarette smoking: an independent risk factor for impotence? Am J Epidemiol 140: 1003–1008, 1994. 20. World Health Organization: Tobacco or Health: A Global Status Report. Geneva, World Health Organization. 1997.
UROLOGY 62 (3), 2003
PRELIMINARY REPORT OF ASSOCIATION OF CHRONIC DISEASES AND ERECTILE DYSFUNCTION IN MIDDLE-AGED MEN IN JAPAN YOSHIO NAYA, YOICHI MIZUTANI, ATSUSHI OCHIAI, JINTETSU SOH, AKIHIRO KAWAUCHI, AKIRA FUJITO, NAOTO NAKAMURA, TOSHIHIKO ONO, NORIYUKI IWAMOTO, TADASHI AOKI, KEN MARUMO, MASARU MURAI, AND TSUNEHARU MIKI
ABSTRACT Objectives. To investigate the effect of chronic diseases on erectile dysfunction (ED) in Japanese middleaged men using the International Index of Erectile Function, 5-item version (IIEF-5). Methods. The subjects consisted of 640 healthy men and 396 men with chronic disease who responded to the IIEF-5 questionnaire (mean age 43.6 ⫾ 8.3 years, range 30 to 59). The incidence and severity of ED were calculated in three age groups (30 to 39, 40 to 49, and 50 to 59 years). Results. The incidence of hypertension, cardiac disease, diabetes mellitus, and chronic renal failure was associated with the incidence and severity of ED, as was age. In stepwise multivariate logistic regression analysis, cardiac disease was the strongest independent risk factor (odds ratio [OR] 6.5), followed by diabetes mellitus (OR 5.9), chronic renal failure (OR 3.9), hypertension (OR 2.0), and age (OR 1.8). Conclusions. The results of this study demonstrated that the risk of ED increases with the presence of cardiac disease, diabetes mellitus, chronic renal failure, and hypertension in middle-aged men in Japan. UROLOGY 62: 532–536, 2003. © 2003 Elsevier Inc.
I
t is well known that aging and chronic diseases such as diabetes mellitus, chronic renal failure (CRF), hepatic failure, and vascular disease are associated with erectile dysfunction (ED).1–3 ED is a severe problem for middle-aged men that negatively affects their quality of life. Although previous studies have shown the relationships between ED and chronic diseases, as well as between ED and age,1–15 a limited number of investigations have described the association of ED with a variety of independent risk factors.2,6,16 In addition, different methods were used for the evaluation of ED in each study. Furthermore, the internationally esFrom the Department of Urology, Kyoto Prefectural University of Medicine; Department of Urology, Rakuwakai-Marutamachi Hospital; First Department of Internal Medicine, Kyoto Prefectural University of Medicine; Department of Urology, Toujinkai Hospital; Department of Urology, Kyoto First Red-Cross Hospital; Department of Urology, Nishijin Hospital, Kyoto; and Department of Urology, Keio University School of Medicine, Tokyo, Japan Reprint requests: Yoichi Mizutani, M.D., Department of Urology, Kyoto Prefectural University of Medicine, KawaramachiHirokoji, Kyoto 602-8566, Japan Submitted: January 30, 2003, accepted (with revisions): March 27, 2003
532
© 2003 ELSEVIER INC. ALL RIGHTS RESERVED
tablished scales should be used for the assessment of ED. Rosen et al.17 reported on the International Index of Erectile Function (IIEF), which has been shown to be a cross-culturally and psychometrically valid measure of ED. It has high sensitivity and specificity for evaluating the effects of treatment in patients with ED of broad-spectrum etiology. An abridged 5-item version of the IIEF (IIEF-5) has been created from the 15-item IIEF.18 It is a brief, reliable, and valid self-administered questionnaire of five items and is favorable for determining the presence and severity of ED. ED is a greater problem for middle-aged men than for elderly men. We assessed the erectile function in Japanese middleaged men with chronic disease and compared each disease as a risk factor for ED using the IIEF-5. MATERIAL AND METHODS The subjects comprised 1036 Japanese male residents of Tokyo, Kyoto, and Osaka who responded to the IIEF-5 questionnaire and a survey on health status (age, present illnesses, and previous history of medication, hospitalization, and surgery) between December 1997 and September 1999 (response rate 65.6%). The questionnaires were self-administered at 0090-4295/03/$30.00 doi:10.1016/S0090-4295(03)00383-2
TABLE I. Characteristics of 1036 men Age (yr) Group Control (n ⫽ 640) Chronic disease* (n ⫽ 396) Each disease Hypertension (n ⫽ 84) Cardiac disease (n ⫽ 17) Hyperlipidemia (n ⫽ 34) Hyperuricemia (n ⫽ 17) Diabetes mellitus (n ⫽ 47) Peptic ulcer (n ⫽ 59) Allergic disease (n ⫽ 24) Chronic renal failure (n ⫽ 35) Disc hernia (n ⫽ 12) Others (n ⫽ 135)
41.4 ⫾ 8.0 47.2 ⫾ 7.3† 51.4 51.4 46.4 46.9 51.5 45.4 48.4 49.5 45.2 46.0
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
4.4† 8.5† 7.6† 7.4 6.5† 10.9† 6.8† 8.4† 8.8† 7.1†
IIEF-5 Score 19.4 ⫾ 6.9 17.1 ⫾ 8.1‡ 15.4 8.5 14.0 18.7 11.8 16.8 21.0 12.9 16.3 19.9
⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾ ⫾
8.7‡ 7.7‡ 9.2‡ 8.2 8.3‡ 8.3§ 6.6㛳 8.2‡ 9.2 6.3
Data presented as the mean ⫾ standard deviation. * Of the 396 patients, 68 had duplicate disease. † Mann-Whitney U test, vs. control significantly greater, P ⬍0.0005. ‡ Mann-Whitney U test, vs. control significantly less, P ⬍0.0005. § Mann-Whitney U test, vs. control significantly less, P ⬍0.05. 㛳 Mann-Whitney U test, vs. control significantly greater, P ⬍0.05.
home, and no attempt was made to validate the responders’ answers. Subject age ranged from 30 to 59 years. They consisted of 640 healthy controls and 396 men with chronic disease. The 640 healthy controls were employees of 10 pharmaceutical companies who responded to the questionnaires completely and had no history of present or previous illness. The 396 men with chronic disease were patients who had visited the clinics of five institutions (Kyoto Prefectural University of Medicine, Kyoto Miniren-Chuo Hospital, Toujinkai Hospital, Rakuwakai-Marutamachi Hospital, and RakuwakaiOtowa Hospital). Table I shows the characteristics of the 1036 men. The mean age of the patients with chronic disease was significantly greater than that of the healthy controls (P ⬍0.0001). The mean IIEF-5 score of those with chronic disease was significantly lower than that of the healthy controls (P ⬍0.0001). Thirty-four patients with CRF undergoing hemodialysis did not have diabetes. Other diseases consisted of otorhinolaryngologic diseases (n ⫽ 15), chronic dermatitis (n ⫽ 11), hemorrhoids (n ⫽ 11), orthopedic diseases (n ⫽ 11), urolithiasis (n ⫽ 11), respiratory infection (n ⫽ 10), cerebral infarction (n ⫽ 6), chronic gastritis (n ⫽ 6), urinary tract infection (n ⫽ 6), chronic hepatitis (n ⫽ 5), dental diseases (n ⫽ 5), asthma (n ⫽ 4), chronic nephritis (n ⫽ 4), chronic prostatitis (n ⫽ 4), gall bladder stone (n ⫽ 4), ophthalmologic diseases (n ⫽ 4), colitis (n ⫽ 3), angiitis (n ⫽ 2), chronic pancreatitis (n ⫽ 2), colon polyp (n ⫽ 2), herpes zoster (n ⫽ 2), hyperthyroidism (n ⫽ 2), inguinal hernia (n ⫽ 2), benign prostatic hyperplasia (n ⫽ 1), rheumatoid arthritis (n ⫽ 1), and ulcerative colitis (n ⫽ 1). We used the Japanese version of the IIEF-5, as previously described.5 The IIEF-5 questionnaire was self-administered in the subjects’ homes. ED was diagnosed when the IIEF-5 score was less than 22.18 We evaluated the incidence of ED by the IIEF-5 score in each age group (30 to 39, 40 to 49, and 50 to 59 years). The ED severity was classified into five categories in each age group: no ED, IIEF-5 score 22 to 25; mild ED, IIEF-5 score 17 to 21; mild-to-moderate ED, IIEF-5 score 12 to 16; moderate ED, IIEF-5 score 8 to 11; and severe ED, IIEF-5 score 1 to 7.18 The incidence and severity were compared between patients with chronic disease and healthy controls using the MannWhitney U test and one-way analysis of variance (ANOVA). UROLOGY 62 (3), 2003
Log likelihood stepwise multivariate logistic regression analysis was performed on the incidence of ED regarding age and each chronic disease. All statistical analyses were performed using Statistical Package for Social Sciences, version 10 (SPSS, Chicago, Ill). Statistical significance was set at P ⬍0.05 in all analyses.
RESULTS The incidence of ED in controls and those with chronic disease in each age group is shown Table II. By one-way ANOVA, the ED incidence was associated with age (F ⫽ 37.7, P ⬍0.0001), diabetes (F ⫽ 30.9, P ⬍0.0001), hypertension (F ⫽ 22.7, P ⬍0.0001), CRF (F ⫽ 21.5, P ⬍0.0001), cardiac disease (F ⫽ 15.1, P ⬍0.0001), and hyperlipidemia (F ⫽ 7.3, P ⫽ 0.007). The ED incidence in patients with chronic diseases at 50 to 59 years was significantly greater than that in patients at 30 to 39 years (P ⬍0.0001). The ED incidence in patients with hypertension or CRF was significantly greater than that in controls older than 40 years (P ⬍0.05). The ED incidence in patients with cardiac disease or diabetes was significantly greater than that in controls older than 50 years (P ⬍0.005). The ED severity in controls and patients with each chronic disease is shown in Table III. By oneway ANOVA analysis, the severity of ED was associated with age (F ⫽ 18.3, P ⬍0.0001), diabetes (F ⫽ 11.9, P ⬍0.0001), cardiac disease (F ⫽ 8.8, P ⬍0.0001), CRF (F ⫽ 6.9, P ⬍0.0001), hypertension (F ⫽ 5.9, P ⬍0.0001), and hyperlipidemia (F ⫽ 4.0, P ⫽ 0.003). In patients with hypertension, the prevalence of mild and severe ED was significantly greater (P ⬍0.05 and P ⬍0.005, respectively) than in controls. In patients with CRF, 533
TABLE II. Incidence of ED 30–39 yr Control Chronic disease* Hypertension* Cardiac disease* Hyperlipidemia㛳 Diabetes mellitus* Hyperuricemia Peptic ulcer Allergic disease Chronic renal failure* Disc hernia Others
33.0 39.7 25.0 66.7 83.3 75.0 33.3 18.2 18.2 57.1 33.3 38.5
40–49 yr
(101/306) (29/73) (1/4) (2/3) (5/6) (3/4) (1/3) (2/11) (2/11) (4/7) (1/3) (10/26)
37.0 43.5 66.7 100.0 57.1 64.7 12.5 40.0 0 78.6 40.0 29.0
50–59 yr
(77/208) (64/147) (20/30)‡ (2/2) (8/14) (11/17) (1/8) (6/15) (0/6) (11/14)‡ (2/5) (18/62)
42.1 64.8 70.0 91.7 64.3 92.3 66.7 60.6 42.9 92.9 75.0 46.8
Total
(53/126) (114/176)† (35/50)§ (11/12)§ (9/14) (24/26)§ (4/6) (20/33) (3/7) (13/14)§ (3/4) (22/47)
36.1 52.3 66.7 88.2 64.7 80.9 35.3 47.5 20.8 80.0 50.0 37.0
(231/640) (207/396)† (56/84)† (15/17)† (22/34)§ (38/47)† (6/17) (28/59) (5/24) (28/35)† (6/12) (50/135)
KEY: ED ⫽ erectile dysfunction; ANOVA ⫽ analysis of variance. Data presented as the percentage, with the numbers in parentheses. * One-way ANOVA, P ⬍0.0001. † Mann-Whitney U test, vs. control, P ⬍0.0001. ‡ Mann-Whitney U test, vs. control, P ⬍0.05. § Mann-Whitney U test, vs. control, P ⬍0.005. 㛳 One-way ANOVA, P ⫽ 0.007.
TABLE III. Severity of ED in middle-aged men No ED Control Chronic disease* Hypertension* Cardiac disease* Hyperlipidemia¶ Hyperuricemia Diabetes mellitus* Peptic ulcer Allergic disease Chronic renal failure* Disc hernia Others
63.9 47.7 33.7 11.8 35.3 64.7 20.5 52.5 79.2 20.6 50.0 63.2
(409/640) (189/396)† (28/83)† (2/17)† (12/34)# (11/17) (9/44)† (31/59) (19/24) (7/34)† (6/12) (86/136)
Mild to Moderate ED
Mild ED 13.6 19.7 26.5 11.8 11.8 2.1 18.2 11.9 4.2 23.5 16.7 21.3
(87/640) (78/396)‡ (22/83)‡ (2/17) (4/34) (1/17) (8/44) (7/59) (1/24) (8/34)‡ (2/12) (29/136)
Moderate ED
2.8 (18/640) 8.4 (54/640) 3.5 (14/396) 6.3 (25/396) 3.6 (3/83) 9.7 (8/83) 0 11.8 (2/17) 8.8 (3/34) 8.8 (3/34) 2.1 (1/17) 2.1 (1/17) 4.5 (2/44) 11.4 (5/44) 5.1 (3/59) 6.8 (4/59) 0 8.3 (2/24) 11.8 (4/34)‡ 8.8 (3/34) 0 8.3 (1/12) 0.7 (1/136) 2.9 (4/136)**
Severe ED 11.3 22.7 26.5 64.6 35.3 17.6 45.4 23.7 8.3 35.3 25.0 11.8
(72/640) (90/396)§ (22/83)㛳 (11/17)§ (12/34)§ (3/17) (20/44)§ (14/59)㛳 (2/24) (12/34)§ (3/12) (16/136)
Abbreviations as in Table II. Data presented as the percentage, with the number in parentheses. * One-way ANOVA, P ⬍0.0001. † Vs. control, significantly less, P ⬍0.0001. ‡ Vs. control, significantly greater, P ⬍0.05. § Vs. control, significantly greater, P ⬍0.0001. 㛳 Vs. control, significantly greater, P ⬍0.005. ¶ One-way ANOVA, P ⫽ 0.003. # Vs. control, significantly less, P ⬍0.005. ** Vs. control, significantly less, P ⬍0.05.
the prevalence of mild, mild-to-moderate, and severe ED was significantly greater (P ⬍0.05, P ⬍0.05, and P ⬍0.0001, respectively) than in controls. The prevalence of severe ED in those with cardiac disease, diabetes, hyperlipidemia, or peptic ulcer was significantly greater (P ⬍0.0001, P ⬍0.0001, P ⬍0.0001, and P ⬍0.005, respectively) than in controls. The ED severity in patients with cardiac disease was significantly greater than in those with hypertension, hyperlipidemia, peptic ulcer, allergic disease, CRF, disc hernia, and others (P ⬍0.05), but it was equivalent to that in those 534
with diabetes. The ED severity in patients with diabetes was significantly greater than that in those with hypertension, peptic ulcer, allergic disease, and others (P ⬍0.05), but it was equivalent to that in those with CRF and hyperlipidemia. Log likelihood stepwise logistic regression analysis was performed for ED incidence versus each chronic disease or age. Cardiac disease was the strongest risk factor on the basis of its odds ratio (OR) of 6.7 (95% confidence interval [CI] 1.4 to 31.3). Diabetes was the second strongest risk factor (OR 5.9, 95% CI 2.8 to 12.3), followed by CRF (OR UROLOGY 62 (3), 2003
3.9, 95% CI 1.6 to 9.5), hypertension (OR 2.1, 95% CI 1.3 to 3.5), and age older than 50 years (OR 1.8, 95% CI 1.3 to 2.5). Diabetes was the most significant independent risk factor for ED (chi-square 30.0, P ⬍0.0001), followed in order by CRF (chisquare 23.7, P ⬍0.0001), age older than 50 years (chi-square 22.0, P ⬍0.0001), hypertension (chisquare 8.1, P ⫽ 0.005), and cardiac disease (chisquare 7.5, P ⫽ 0.006). We also analyzed the relationship of ED severity with age or chronic disease using stepwise logistic regression analysis. For intermediate ED (IIEF-5 score 16 or less), cardiac disease was the strongest risk factor as determined by its OR of 7.6 (95% CI 2.3 to 24.4). Diabetes was the second strongest risk factor (OR 5.4, 95% CI 2.9 to 10.1), followed by CRF (OR 3.4, 95% CI 1.7 to 7.1), and hyperlipidemia (OR 2.9, 95% CI 1.4 to 6.0). Diabetes was the most significant independent risk factor for ED (chi-square 35.6, P ⬍0.0001), followed in order by cardiac disease (chi-square 25.1, P ⬍0.0001), CRF (chi-square 11.4, P ⫽ 0.001), and hyperlipidemia (chi-square 9.0, P ⫽ 0.003). For severe ED (IIEF-5 score 7 or less), cardiac disease was the strongest risk factor as determined by its OR of 10.2 (95% CI 3.6 to 28.8). Diabetes was the second strongest risk factor (OR 4.1, 95% CI 2.2 to 7.7), followed by age older than 50 years (OR 2.8, 95% CI 1.7 to 4.4), and hyperlipidemia (OR 2.3, 95% CI 1.1 to 5.0). Diabetes was the most significant independent risk factor for ED (chi-square 36.4, P ⬍0.0001), followed in order by cardiac disease (chi-square 36.3, P ⬍0.0001), age older than 50 years (chi-square 11.2, P ⫽ 0.001), and hyperlipidemia (chi-square 4.5, P ⫽ 0.034). COMMENT In the Massachusetts Male Aging Study, the probability of complete ED was 39% in those treated for cardiac disease, 15% in those treated for hypertension, and 28% in those treated for diabetes.6 In the current study, the probability of severe ED was 64.6% in those with cardiac disease, 26.5% in those with hypertension, and 45.4% in those with diabetes. The probability of severe ED in those with cardiac disease, hypertension, or diabetes was greater compared with the results in the Massachusetts Male Aging Study. In the current study, the ED incidence in those with CRF was 79.4%. In previous studies of patients requiring dialysis, 45% to 86% of men had ED.4,7 ED severity was associated with age on the basis of one-way ANOVA analysis. The probability of severe ED in patients with chronic disease at the age of 50 to 59 years was approximately twofold greater than that at age 30 to 39 years. In the Massachusetts Male Aging Study, the probability of complete ED triUROLOGY 62 (3), 2003
pled from 5% to 15% between subject ages of 40 and 70 years.6 In the current study, cardiac disease and hypertension were risk factors for mild ED, moderate ED, and severe ED in multivariate logistic regression analyses. Hyperlipidemia was a risk factor for severe ED and intermediate ED in multivariate logistic regression analysis. These results are consistent with those of previously published studies.9 –13 It is well known that hyperlipidemia is one of the main causes of cardiovascular disease.8 Diabetes is a well-known illness associated with ED.13–15 In the current study, the risk of ED was approximately sixfold greater in diabetic men than in nondiabetic men at middle age, when using a cutoff of 21 for the IIEF-5. In addition, diabetes was a risk factor for severe ED and intermediate ED with an OR of 5.4 and 4.1, respectively. Several studies have reported that the risk of ED in men with diabetes was three to fourfold greater in European countries13,14 and in the United States.6 CRF is also well recognized as an illness that causes ED.4,7 In the current study, CRF was a risk factor for ED in multivariate logistic regression analysis. The risk of ED was approximately four times greater in men undergoing hemodialysis than in men without CRF at middle age when using a cutoff of 21 for the IIEF-5 (mild ED). When using cutoff values of 7 or 16 for the IIEF-5, CRF was not a risk factor for ED. Although diabetes is associated with ED in patients requiring hemodialysis,4,7 we excluded patients with diabetes who required hemodialysis because of age mismatching in the current study. In the current study, the OR of ED for men with diabetes was greater than in several European reports13,14 when using a cutoff of 21 for the IIEF-5. When using a cutoff of 7 for the IIEF-5, the risk of ED for diabetic men was similar to that of previous studies.13,14 The incidence of ED in patients with cardiac disease or diabetes was greater than in several Western reports.6,13,14 These differences may have been due in part to the different method of evaluation for ED used between the previous reports and the current one. In the present study, the incidence of severe ED in men with cardiac disease was greater than that in men with diabetes. Hyperlipidemia was a risk factor for severe ED and intermediate ED, but not for mild ED. Conversely, CRF was a risk factor for mild ED but not for intermediate ED or severe ED. In addition, no association was found with mild to moderate ED and chronic disease, except for CRF. These findings suggest that the severity of ED might be related to the vasculogenic condition and that intermediate ED might be related to endocrinologic and neurogenic conditions. In the current study, we did not evaluate the relationship of ED and smoking. Smoking is a risk 535
factor for ED.19 The prevalence of smoking in Japanese men is 59% and in European and American men is 46% and 35%, respectively.20 Additional study is needed concerning the relationship of ED with smoking and chronic diseases. Many men with a chronic disorder already have ED at middle age according to our results. However, the major limitation of this study was that the data collection was limited to self-report. Medical conditions that may be asymptomatic are often unknown by the subject and consequently underreported. Despite the limitation of the current study, the prevalence of ED and the severity were associated with age, cardiac disease, and diabetes in middle-aged Japanese men. CONCLUSIONS The results of the present study demonstrated that chronic disorders such as cardiac disease, hypertension, diabetes, and CRF are risk factors for ED in Japanese middle-aged men. In particular, cardiac disease was the strongest risk factor for ED, followed by diabetes. The current study was a preliminary study and not a cause-specific or random sample observational study. In addition, the data for the current study were obtained by self-report of the subjects, a major limitation for the evaluation of ED in the current study. Additional studies are needed with well-controlled and large numbers of subjects. Although the current study had some limitations, we should educate young men without chronic disorders, as well as patients with chronic disorders in the early stage, to prevent ED and maintain their quality of life. ACKNOWLEDGMENT. To Drs. M. Maegawa and M. Kondo for assistance in obtaining IIEF questionnaires from male dialysis patients. REFERENCES 1. Marumo K, and Murai M: Epidemiology of erectile dysfunction, in Kim YC, and Tan HM (Eds): APSIR Book on Erectile Dysfunction. Asia-Pacific Society for Impotence Research, 1999, pp 15–26. 2. Marumo K, Nakashima J, and Murai M: Age-related prevalence of erectile dysfunction in Japan: assessment by the International Index of Erectile Function. Int J Urol 8: 53–59, 2001. 3. Bortolotti A, Parazzini F, Colli E, et al: The epidemiology of erectile dysfunction and its risk factors. Int J Androl 20: 323–334, 1997.
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