Erectile Dysfunction (ED) is Prevalent, Bothersome and Underdiagnosed in Patients Consulting Urologists for Benign Prostatic Syndrome (BPS)

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1 European Urology European Urology 47 (2005) Erectile Dysfunction (ED) is Prevalent, Bothersome and Underdiagnosed in Patients Consulting Urologists for Benign Prostatic Syndrome (BPS) C.E. Hoesl a, E.M. Woll b, M. Burkart c, J.E. Altwein a, * a Department of Urology, Hospital Barmherzige Brüder, Technical University Munich, Romanstr. 93, München, Germany b Ladenburg, Germany c Medical Affairs, Pfizer GmbH, Karlsruhe, Germany Accepted 19 October 2004 Available online 8 December 2004 Abstract Objectives: The aim of the present study was to determine the prevalence of erectile dysfunction (ED) in patients visiting office-based urologists in Germany because of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and to evaluate the impact of ED on quality of life (QoL) in these patients. Methods: 500 office-based urologists in Germany were invited to evaluate 20 consecutive patients for erectile dysfunction, who presented because of BPH-related LUTS. Physicians provided information on demographic factors, duration and treatment history of BPH, severity of LUTS, ED risk factors, and assessed the patient for the clinical diagnosis of ED. Patients were asked to complete the German version of the IPSS to measure LUTS severity. ED-patients quantified erectile dysfunction and impact on quality of life with validated German questionnaires (Cologne assessment of male erectile dysfunction KEED, and Qol-Med). Results: Office-based urologists were aware of ED in 37.3% of 8768 patients presenting for LUTS before the study, 14.7% of patients were treated for ED. After the study-related assessment, physicians diagnosed ED in 62.1% of these patients and planned treatment in 46.9%. Severity of LUTS and ED prevalence correlated significantly after age-stratification. The incidence of ED was increased in patients with established ED risk factors. Mean QoL-Med score (best QoL: 100, worst QoL: 0) was 53.8 in patients with ED and 50.1 in ED-patients considering treatment. Conclusion: ED is highly prevalent in LUTS patients visiting an office-based urologist and is accompanied by a profound impact on the quality of life. Apparently, even during an urological consultation many ED-patients are hesitant to actively ask for treatment. Sexual issues should become key considerations for physicians managing patients with LUTS, especially since effective and well established oral treatment for ED is available. # 2004 Elsevier B.V. All rights reserved. Keywords: Prevalence; Impotence; Lower urinary tract symptoms (LUTS); Benign prostatic hyperplasia (BPH); Quality of life (QoL) 1. Introduction With the growing life expectancy and absolute number of the elderly, studies on age-related diseases are becoming increasingly important. Age is the major risk factor for erectile dysfunction (ED) defined as the * Corresponding author. Tel ; Fax: address: Dr.Bartha@t-online.de (J.E. Altwein). consistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. The Massachusetts Male Aging Study revealed a prevalence of 52% of ED of any grade among men aged with the incidence rate of complete impotence tripling from 5 to 15% between subjects of 40 and 70 years [1]. Parazzini et al. observed an increasing linear trend of ED with age from 2% (18 39) to 48% (70 years) [2]. These findings were also corroborated /$ see front matter # 2004 Elsevier B.V. All rights reserved. doi: /j.eururo

2 512 C.E. Hoesl et al. / European Urology 47 (2005) by studies conducted in South Australia [3], Finland [4], France [5] and England [6]. Several questionnaires have been developed and validated to quantify impairment of erectile function [7,8]. Braun et al. developed the German Cologne assessment of male erectile dysfunction (KEED) to evaluate erectile dysfunction [9]. Lower urinary tract symptoms (LUTS), often caused by benign prostatic hyperplasia (BPH), are characterized by reduced stream, hesitation, increased frequency, urgency, and nocturia [10 12]. As the most common urological problem with an increased prevalence in patients older than 50 years, LUTS has an enormous impact on the public health system [13]. Treatment options for LUTS include both, invasive procedures and noninvasive therapy [14,15]. Recently, a number of studies revealed an association between ED and LUTS [16 20]. The multinational UrEpik study performed in regions of the UK, the Netherlands, France and Korea demonstrated an unequivocal association between ED and LUTS (p < 0.001) [21]. In a large-scale multinational survey conducted in the US and selected countries in Europe (MSAM-7), LUTS was clearly identified as an independent risk factor for sexual dysfunction in aging men [22]. Health-related epidemiological studies increasingly address quality of life as an important criterion, because it mirrors the real effect of the symptoms on the patient [23]. Men having LUTS reported a significant impairment in their quality of life [24 26]. The presence of a normal sexual desire combined with the inability to physically act on that desire due to ED is also known to impinge considerably on patients quality of life due to growing mental stress and disorders in interpersonal relationships including partnership problems [27 30]. However, it has not been determined, to what degree ED further impairs QoL in LUTS patients. To better understand the impact of the above mentioned findings on the office-based urologist s patient management the present survey evaluated the prevalence and QoL impact of ED in patients visiting an office-based urologist for LUTS. In addition, we were interested whether LUTS can be replicated as an independent risk factor for ED in this specific population. 2. Material and methods In October 2001, standardized and validated questionnaires were sent to 500 urological practitioners. Each of these practitioners was asked to include the first twenty patients presenting with benign prostatic hyperplasia (BPH) into the survey. The following information was requested from the physicians: demographics, co-morbidities, (hypertension, diabetes mellitus, coronary artery disease and hyperlipidemia), duration of BPH and severity of LUTS, treatment history, diagnosis and treatment of ED before the study. ED is a clinical diagnosis that cannot be substituted by a threshold score on any questionnaire or by objective test findings. Thus, physicians were asked for a final clinical ED diagnosis. Furthermore, they were required to indicate planned ED therapy after completion of the study. Patients completed the International Prostate Symptom Score (IPSS) [31,32], a validated eight-item scale based on the evaluation of incomplete emptying, urinary frequency, intermittency, urgency, weak stream, straining, nocturia and bothersomeness. The first seven questions have an ordered categorical response frame that can be scored from 0 to 5 leading to an overall score of 0 to 35. Symptoms were classified as absent (IPSS = 0), mild (IPSS 7), moderate (IPSS 8 19), or severe (IPSS 20). Patients with the clinical diagnosis of ED evaluated erectile function using the Cologne assessment of male erectile dysfunction (KEED), a validated German questionnaire [9]. The six questions assessing the severity of ED (items 3 to 8) were used to calculate a summed score (0 24, score >17: low probability of ED, score 17: high probability of ED). The diseaserelated quality of life in ED-patients was assessed by means of the German version of the QoL Med-Questionnaire ( Quality of life measure for men with erection difficulties ) with a score ranging from 0 (lowest quality of life) to 100 (highest quality of life) [33,23]. All statistical analyses were descriptive or exploratory, performed on SAS software. The association between ED prevalence and LUTS severity was analyzed using the Cochrane-Mantel- Haenzel test after age-stratification of the sample. The association between cardiovascular risk factors and ED-prevalence was analyzed by x 2 statistics. 3. Results A total of 10,000 documentation forms were sent to 500 urological practitioners. Of those, 8768 were returned. Not all urologists were willing to measure or document their patients age, height and weight. Thus, the demographic data could not be obtained for the total of 8768 patients. On average, patients were 63.4 years old (N = 7969, SD = 8.5, Fig. 1). They had an average height of 1.76 m (N = 8462, SD = 0.075) and an average weight of 82.1 kg (N = 8412, SD = 10.6). 95.5% of the entire respondents were diagnosed with benign prostatic hyperplasia (BPH) and 4.5% with malignoma. The questionnaires were filled out by the patient himself. The urologists were requested not to interview the patient Prevalence, severity and therapy of LUTS 6480 of the patients (73.9%) completed the IPSS. Mild LUTS (IPSS = 0 7) were present in 11% of the participants. In 52.4% an IPSS of 8 19 indicated moderate LUTS. 10.5% were suffering from severe LUTS (IPSS = 20 35). The mean IPSS was

3 C.E. Hoesl et al. / European Urology 47 (2005) Table 1 Preceding therapy in LUTS patients with ED BPH treatment N ED diagnosis suprapubic adenomectomy (87.6%) TURP (69.6%) medication (65.1%) Table 2 Age dependence of ED in LUTS patients Age N ED diagnosis Fig. 1. Age distribution of 8768 LUTS patients , the median patients were treated medically, 1335 patients had undergone a surgical intervention (321 suprapubic adenomectomy and 1014 TURP) Erectile dysfunction 3270 (37.3%) patients had been diagnosed with erectile dysfunction before the survey. Of those, 1290 (14.7%) had been treated for ED. Based on the urologist s final clinical judgment after completing the survey, 5446 (62.1%) men were suffering from erectile dysfunction (see Fig. 2). Of those, 968 had undergone invasive treatment (suprapubic adenomectomy: 275, TURP: 693), whereas 3797 had received medication for LUTS (see Table 1) (75.5%) of the ED patients planned ED-treatment after the survey (88.5%) of the 5446 ED-patients completed KEED questionnaires; the average score was A total of 4594 men scoring 17 have been treated for LUTS in the past either by surgical procedures (suprapubic % 40 < % 50 < % 60 < % 70 < % 80 < % no age given % total % adenomectomy: 264, TURP: 694) or medication (3636). ED was common in each age group with incidence rates varying from 58.2 to 72.2% (Table 2). With increasing severity of LUTS assessed by the IPSS the prevalence of erection problems was rising (p < corrected for age-groups, see Table 3) (42.2%) patients in the entire group of respondents had hypertension (21.5%) were diagnosed with coronary artery disease, (22.1%) with hyperlipidemia, and (17.2%) with diabetes mellitus. Comorbidities were not corrected for age, since the onset age and therapy were not known. Erectile dysfunction was more often diagnosed in patients with evaluated risk factors (p < for every risk factor and for number of risk factors, see Table 4). Fig. 2. Diagnosis and treatment of erectile dysfunction before and after completing the survey (N = 8768).

4 514 C.E. Hoesl et al. / European Urology 47 (2005) Table 3 ED prevalence in correlation with LUTS severity years years >75 years Total Diagnosed with ED IPSS (48.4%) 250 (53.6%) 33 (71.7%) 513 (53.4%) (57.6%) 1621 (65.3%) 139 (58.4%) 2815 (62.3%) (64.3%) 392 (73.5%) 44 (77.2%) 640 (71.1%) No IPSS available 392 (63.3%) 767 (70.2%) 63 (64.9%) 1478 (67.7%) total Quality of life 5494 (62.7%) QoL-Med questionnaires assessing the impact of erectile problems on the patients quality of life were returned to us. The average score for LUTS patients was (89.0%) of LUTS patients with the clinical diagnosis of ED completed QoL-Med questionnaires; the average score was 53.8 (Fig. 3). This result indicates that decreased sexual activity due to erection difficulties is a major concern for LUTS patients and has an impact on the LUTS patients quality of life. LUTS patients who intended ED-therapy scored with an average of 50.1, (Fig. 3). These observations are based on incidence rates varying with age. QoL scores after treatment of ED were not available. Results are summarized in Table 5. The answers to the QoL-related question in the KEED reflected a reduced quality of life, too (Fig. 4). Table 4 Additional ED risk factors in LUTS patients ED diagnosis CAD yes 74.5% 1840 no 60.4% 6469 no answer 66.1% 254 hypertension yes 71.0% 3615 no 58.0% 4768 no answer 63.3% 180 diabetes mellitus yes 79.0% 1479 no 60.3% 6823 no answer 63.2% 261 hyperlipidemia yes 74.9% 1873 no 60.1% 6361 no answer 66.9% 329 total 63.6% 8563 N Fig. 3. Quality of life in LUTS patients with ED according to the QoL-Med questionnaire.

5 C.E. Hoesl et al. / European Urology 47 (2005) Table 5 Quality of life in LUTS patients with ED: Qol-Med results [23,33] Very much (%) Quite a lot (%) A little bit (%) Not at all (%) No answer (%) a/b a/b a/b a/b a/b 1. I feel frustrated because of my erection problem. 11.7/ / / / / My erection problem makes me feel depressed. 10.5/ / / / / I feel like less of a man because of my erection problem. 8.5/ / / / / I have lost confidence in my sexual ability. 17.3/ / / / / I worry that I won t be able to get or keep an erection. 20.1/ / / / / My erection problem is always on my mind. 6.2/ / / / / I feel that I have lost control over my erections. 19.7/ / / / / I feel angry because of my erection problem. 5.7/ / / / / I worry about the future of my sex life. 17.7/ / / / / I have lost pleasure in sex because of my erection problem. 13.2/ / / / / I am embarrassed about my problem. 14.1/ / / / / I try to avoid having sex. 12.0/ / / / / I feel different from other men because of my erection problem. 5.4/ / / / / I get less enjoyment out of life because of my erection problem. 5.8/ / / / / I feel guilty about my erection problem. 3.3/ / / / / I am afraid to make the first move towards sex. 16.2/ / / / / I worry that my partner blames herself for my erection problem. 20.8/ / / / / I worry that I m not satisfying her because of my erection problem. 24.0/ / / / /2.2 a: patients diagnosed with ED (N = 4848); b: patients intending ED-treatment (N = 3802). Fig. 4. KEED Quality of life-related question in LUTS patients with ED (N = 5446). 4. Discussion The present study is the only office-based study performed in Germany to assess both the prevalence of erectile dysfunction and the impact of the sexual impairment on the quality of life in LUTS patients. Recently, studies including a multi-national large-scale survey were published, in which the relationships between LUTS and sexual dysfunction in older men were systematically investigated [1,17,22]. In accordance with these studies, we conclude from our results that LUTS is an independent risk factor for erectile dysfunction in an office-based sample. In previous studies, no special emphasis was put on the evaluation of the quality of life in LUTS patients experiencing erectile problems. Herein, we used standardized and validated scales to assess the severity of erectile dysfunction (KEED) and the quality of life (QoL-Med) as reliable tools for the evaluation of the links between LUTS, erectile dysfunction, and QoL [9,22,33]. We found that erectile dysfunction accompanying LUTS had a profound negative impact on quality of life. LUTS patients having ED reported depression, frustration and a loss in self-confidence. In addition, the patients experienced the loss in erectile capacity as a negative influence on the relationship to the partner. Data from a recent placebo-controlled and an open-label study demonstrated that successful EDtreatment with sildenafil significantly improved selfesteem, confidence, and relationships [34,35]. Co-morbidities known to cause erectile problems, such as coronary artery disease, diabetes mellitus, hypertension and hyperlipidemia, further increased the prevalence of erectile dysfunction in LUTS patients. Therefore, a multidisciplinary approach to the management of erectile dysfunction in LUTS patients is reasonable and should certainly be undertaken. We also examined whether surgical or nonsurgical treatment of BPH was associated with the prevalence of ED. The results obtained imply a lower incidence rate of ED when BPH was treated non-invasively. It is known, that medical therapies for BPH can impact to varying degrees sexual capacity [36,37]. In the survey presented herein, different drug options for BPH and their potential adverse effects on erectile dysfunction

6 516 C.E. Hoesl et al. / European Urology 47 (2005) were not explicitly studied. We refer the reader to a recently published review by Carbone et al. summarizing 73 papers on medical therapies for BPH with a focus on the effects of different pharmacological agents on sexual function [38]. Thus far, the mechanism underlying the relationship between LUTS and ED remains unknown. Four leading theories of how these diseases interrelate were suggested, e.g. the nitric oxide synthase/nitric oxide theory [39], autonomic hyperactivity effects on LUTS and ED [40], increased Rho kinase activation/downregulation of endothelin-b receptor sites [41] and prostate and penile artherosclerosis [42]. Anatomic factors due to the enlarged prostate were proposed to have advert effects on erectile function [43]. Psychological factors are likely to promote ED in LUTS patients, since it is obvious that LUTS can cause a high level of stress that might negatively affect erectile capacity. Further research is needed to clarify biochemical, anatomic and sociopsychological aspects of ED in LUTS patients. Remarkably, the treating urologist was not aware of the patients ED before completing the survey in about 40% of ED-patients. This shows that men hesitate to admit sexual problems and to report them spontaneously to the urologist. Thus, it can be assumed that many cases of ED in LUTS patients remain unmanaged. This study may contribute to increase the awareness of physicians that disease management for LUTS patients should include anamnesis, diagnosis and treatment of erectile dysfunction. In particular, LUTS patients should be informed routinely on potential adverse effects of LUTS therapy on their sexual life. Considering the fact that according to the findings in this study ED decreases the quality of life of LUTS patients significantly including their relationship to their partners, alleviating this condition should be a main concern. 5. 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