The impact of irritative lower urinary tract symptoms on erectile dysfunction in aging Taiwanese males

Abstract

Objective. This study assessed the possible associations between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging Taiwanese males and investigated the impact of various aspects of LUTS on ED.

Methods. A free health screening for aging males (≥40 years old) was conducted in Kaohsiung Medical University Hospital. All the subjects had completed clinical data and answered questionnaires. ED and LUTS were assessed by validated symptom scales: the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS).

Results. A total of 339 eligible patients enrolled in this study with a mean age of 60.1 years old. In multiple logistic regression analysis, age and IPSS (p < 0.001 and p = 0.013, respectively) were significantly associated with ED after controlling other comorbidities. In a further age-adjusted multiple regression analysis, our results showed that irritative symptoms (p = 0.042) have a more significant association with ED than the obstructive symptoms (p = 0.101).

Conclusions. Our results indicate that age and LUTS are the two most independent risk factors for ED. Aging Taiwanese males with LUTS are at increasing risk for ED, especially for those with significant irritative symptoms.

Keywords:

• Lower urinary tract symptoms
• erectile dysfunction
• irritative
• International prostate symptom score

Introduction

Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) are common disorders in the elderly and both have been reported to be associated with increasing prevalence with aging [1,2]. In 1994, the famous Massachusetts Male Aging Study showed that 34.8% of men aged 40 to 70 years old had moderate to severe ED which was strongly related to age, diabetes, depression and cardiovascular disease. In this study, LUTS were not considered potential risk factors for ED [3]. In recent years, many community-based studies have been conducted to ascertain the associations between LUTS and ED. Most of published studies suggest that these two conditions are linked, indicating that the prevalence of ED is associated with the presence and severity of LUTS [4–6]. Some limitations still remain in assessing the connection between these two disorders because of poorly controlling the effects of age and other comorbidities. In terms of epidemiology, there is also a great diversity in different ethnic communities and countries [2,7,8]. Furthermore, few studies about the impact of various aspects of LUTS on ED were reported [9,10]. Hence, the present study aims at identifying the possible associations between LUTS and ED in aging Taiwanese males, and investigating the impact of various aspects of LUTS on ED.

Methods

A total of 339 men older than 40 years underwent a free health screening at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. During the investigation, sociodemographic characteristics and medical history were assessed by the urologists. Detailed physical examinations, such as weight, height, blood pressure, digital rectal examination and evaluation of prostate volume by transrectal ultrasonography, were also performed. Blood samples were taken for biochemical analysis, including serum testosterone level and prostate-specific antigen (PSA) level.

This study was approved by hospital's institutional Review Broad. All subjects provided informed consent before participation. In order to evaluate ED and LUTS, all participants were asked to complete two validated questionnaires: the abridged version of International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS). Patients with ED were defined as those who subjectively had the problem of being unable to achieve or maintain a sufficient erection for sexual intercourse [11]. The confirmed diagnosis of ED was decided by IIEF-5 <21 [12]. The IPSS questionnaire consists of two major groups, obstructive symptoms (incomplete emptying, intermittency, weak stream and hesitancy) and irritative symptoms (frequency, urgency and nocturia). The severity of each category of LUTS was recorded with a score from 0 (not at all) to 5 (always). And the quality of life (QoL) associated with LUTS was also evaluated by using the disease-specific QoL question score from the IPSS. It was phrased as follows: ‘If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?’ The answering scale ranged from 0 (delighted) to 6 (terrible) [13].

Vascular risk factors that may be associated with ED were completely reviewed. Hypertension was defined as a systolic pressure of >140 mm Hg or diastolic pressure of >90 mm Hg. Diabetes mellitus (DM) was defined as the fasting blood glucose concentration level of >126 mg/dl. Hyperlipidemia was defined as a total cholesterol level of >200 mg/dl or triglycerides levels of >200 mg/dl. A ‘smoker’ was defined as one who has smoked 10 cigarettes per day for more than 6 months. An ‘alcohol drinker’ was defined as one who has consumed alcohol every week for over 6 consecutive months [14]. Individuals, who were diagnosed previously as hypertension, DM or hyperlipidemia, but now under control by regular medication, were also recruited in the study.

The excluded criteria were: (i) Subjects without an active sexual life with a regular partner for 6 months before receiving the health investigation; (ii) Subjects with abnormal PSA level (>4 ng/ml); (iii) Subjects who had undergone surgical or medical therapy for BPH or ED; (iv) Subjects with primary hypoactive sexual desire or ED due to anatomical abnormality of the penile; (v) Subjects who had histories of neurological disease, urological calculi, urinary tract infection or malignancy; and (vi) Subjects had any psychiatric or substance abuse disorders.

The frequencies of clinical variables as well as various aspects of LUTS were compared between two different groups according to ED prevalence using the chi square and Student's t-tests. Multiple logistic regression analysis was used to determine the independent factors influencing ED. Odds ratios (ORs) were also calculated in multiple logistic regression analysis. p < 0.05 was considered statistically significant.

Results

Table I showed the demographic and clinical data of subjects. There were 339 eligible subjects with mean (standard deviation, range) age of 60.1 (8.2, 44–87) years old. The mean IIEF-5 score was 14.9 (8.1, 1–25), and the mean IPSS was 8.4 (6.8, 0–32), as for t subgroups of IPSS, the mean irritative symptoms score and obstructive symptoms score were 3.9 (3.7, 0–15) and 4.5 (3.7, 0–17), respectively.

Table I.  Principal characteristics (n = 339 subjects).

	Mean ± SD	Range
Age, years	60.1 ± 8.2	44–87
BMI	24.5 ± 3.0	17.0–41.1
IIEF-5 score	14.9 ± 8.1	1–25
IPSS	8.4 ± 6.8	0–32
Obstructive score	4.5 ± 3.7	0–17
Irritative score	3.9 ± 3.7	0–15
QoL question score	2.3 ± 1.2	0–6
Prostate volume (ml)	29.9 ± 16.6	10–118
Testosterone (ng/dl)	379.6 ± 119.6	80–823
PSA (ng/ml)	1.3 ± 1.0	0.04–3.95

BMI, body mass index; IIEF, International index erectile function; IPSS, International prostate symptom score; QoL, quality of life; PSA, prostate-specific antigen.

The characteristics of two groups between subjects with and without ED were concluded in Table II, which showed that the frequencies of hypertension (p = 0.03) and DM (p = 0.04) were significantly greater in patients with ED. Among the quantitative variables, age (p < 0.01), prostate volume (p = 0.04), QoL question score (p < 0.01), and IPSS (p < 0.01) were significantly different between subjects without and with ED. In the following multiple logistic regression analysis (Table III), age (OR = 1.098, p < 0.001) and IPSS (OR = 1.083, p = 0.013) were identified as the two most independent risk factors for ED. To further identify the impact of various aspects of LUTS on ED, we performed an age-adjusted multiple regression analysis, including irritative and obstructive LUTS. Our result pointed out that the irritative symptoms (p = 0.042) have a more significant association with ED than the obstructive symptoms (p = 0.101) (Table IV). We further evaluated the statistical effect of irritative symptoms one by one on the erectile function (not shown). The results showed that the scores of frequency, urgency and nocturia were all significantly higher in subjects with ED (p < 0.01).

Table II.  Result of univariate analysis of the association between qualitative/quantitative variables and ED.

Variable	Subjects without ED (n = 96)	Subjects with ED (n = 243)	p
Hypertension (%)	27.0	38.2	0.03
No, n	70	150
Yes, n	26	93
DM (%)	13.5	18.5	0.04
No, n	83	198
Yes, n	13	45
Hyperlipidemia (%)	18.7	13.5	0.15
No, n	78	210
Yes, n	18	33
CAD (%)	10.4	16.4	0.10
No, n	86	203
Yes, n	10	40
Alcohol drinker (%)	11.4	12.3	0.49
No, n	85	213
Yes, n	11	30
Smoker (%)	13.5	19.3	0.13
No, n	83	196
Yes, n	13	47
Mean (SD)
Age (years)	56.0 (6.5)	61.8 (8.3)	<0.01
BMI (kg/m^2)	24.3 (3.0)	24.9 (3.0)	0.07
Prostate volume (ml)	27.0 (11.2)	31.1 (18.2)	0.04
Testosterone (ng/dl)	375.7 (102.4)	381.2 (125.9)	0.70
PSA (ng/ml)	1.1 (0.9)	1.3 (1.1)	0.06
QoL question score	1.7 (1.1)	2.5 (1.2)	<0.01
Total IPSS	5.2 (5.0)	9.7 (7.0)	<0.01
Irritative score	2.3 (2.8)	4.5 (3.8)	<0.01
Obstructive score	2.8 (2.7)	5.2 (3.8)	<0.01

ED, erectile dysfunction; DM, diabetes mellitus; CAD, coronary artery disease; SD, standard deviation; BMI, body mass index; PSA, prostate-specific antigen; IPSS, International prostate symptom score; QoL, quality of life.

Table III.  Results of multivariate logistic regression analysis of the association between qualitative/quantitative variables and ED.

Variable	Adjusted odds ratios (95% C.I.)	p
Hypertension	0.984 (0.51–1.89)	0.961
DM	0.809 (0.36–1.79)	0.603
Hyperlipidemia	0.703 (0.33–1.48)	0.356
CAD	1.163 (0.50–2.69)	0.724
Alcohol drinker	1.268 (0.53–3.00)	0.590
Smoking	1.994 (0.90–4.40)	0.088
Age (years)	1.098 (1.05–1.14)	<0.001
BMI (kg/m^2)	0.986 (0.90–1.08)	0.766
Prostate volume (ml)	1.002 (0.98–1.02)	0.844
Testosterone (ng/dl)	1.002 (0.99–1.00)	0.210
PSA (ng/ml)	1.036 (0.76–1.40)	0.820
QoL question score	1.267 (0.92–1.73)	0.139
Total IPSS	1.083 (1.01–1.15)	0.013

ED, erectile dysfunction; DM, diabetes mellitus; CAD, coronary artery disease; SD, standard deviation; BMI, body mass index; PSA, prostate-specific antigen; IPSS, International prostate symptom score; QoL, quality of life.

Table IV.  Results of age-adjusted multiple regression analysis of the association between various aspects of LUTS and ED.

	β coefficient	β standard error	p
Age	0.089	0.019	<0.001
Irritative IPSS	0.119	0.058	0.042
Obstructive IPSS	0.096	0.058	0.101

ED, erectile dysfunction; LUTS, lower urinary tract symptoms; IPSS, International prostate symptom score.

Discussion

Traditionally, ED was known to correlate with aging and vascular risk factors such as hypertension and diabetes [3,14]. In this study, LUTS, prostate volume, QoL and these vascular risk factors were found to be significantly associated with ED in the univariate analysis. However, aging and LUTS were the two most independent risk factors for ED after controlling age and other comorbidities in the results of multivariate analyses.

Despite the fact that accumulating evidence has identified LUTS as a risk factor for ED in aging men, the precise aetiology between these two disorders has not been well-established. According to previous statistic findings and pathophysiological evidence, several leading mechanisms have been discussed, including a decrease of nitric oxide /nitric oxide synthase (NO/NOS) in the endothelium, an increased Rho-kinase activity and calcium sensitivity, an atherosclerosis related to pelvic ischaemia, α-adrenergic receptor imbalance and an autonomic hyperactivity [15,16]. However, cumulative literatures have now identified that impaired NO/NOS-mediated pathway and endothelial dysfunction play a key role to the development of both conditions in aging population.

In 1995, Carrier et al. [17] found a reduction in NOS activity in aging rats. Aging is also recognised to induce endothelial cell dysfunction, impaired expression of penile NOS and decreased NO bioavailability, resulting in reduced cavernosal smooth muscle relaxation and erectile impairment [18,19]. In 2004, Burnett AL further demonstrated that nNOS may initiate cavernosal tissue relaxation, while activating eNOS may facilitate attainment and maintenance of full erection [20]. To date, the important role for NO/NOS pathway in the relaxation of male penile erectile tissue has been widely accepted [21]. In the past few years, this pathway has also gained increasing recognition as an important neurotransmitter and cell mediator with a broad range of functions in the lower urinary tract. In human prostate, the eNOS is related to the maintenance of local vascular perfusion, whereas the nNOS is mainly involved in the control of smooth muscle tone and glandular function [22]. The results of current trials further identified that the NOS gene expression is reduced with aging in prostate tissue and might be a factor for increased smooth muscle tone associated with LUTS [23]. Recently, few genetic researches have further identified the 894T carriers of eNOS gene polymorphism may implicate a genetic susceptibility factor for ED as well as LUTS [24,25]. Extending the similarity between the relaxation of smooth muscle in the prostate and erectile process, decreased NOS activity might result in altered prostatic and cavernosal muscular tone and subsequently contribute to the dynamic aspect of LUTS and ED [26].

LUTS include irritative and obstructive symptoms. In the age-adjusted regression analyses, our result further demonstrated the irritative LUTS had more significant impact on ED prevalence in aging Taiwanese males. To date, few studies have discussed the impact of various aspects of LUTS on ED. In 2004, Elliott et al. [9] firstly described a consistent negative correlation between obstructive IPSS and the sexual health inventory for men questionnaire (SHIM) score across age groups, with the strongest effect for men aged 60 to 70 years old. However, rising studies found that sexual dysfunction may be more closely associated with irritative ones. Aslan et al. [6] reported that the association between SHIM score and each item of IPSS showed significant correlation for urgency, straining and nocturia when age was controlled. In another clinical sample comprised 1271 men attending urology clinics with LUTS in 12 countries [10], the age-adjusted odds ratios of sexual dysfunction were especially raised in relation to irritative urinary symptoms. Tsao et al. [27] also found that the irritative IPSS showed a significant correlation with IIEF-5 severity across all age groups.

The mechanisms correlated to the irritative symptoms with ED remains unclear. Engström's study [28], which enrolled 1008 men aged 40 to 80 years old living in Sweden, showed that irritative symptoms appear to reduce more QoL than obstructive and post-micturition symptoms, suggesting biopsychosocial pathogenesis may be a factor that linked the irritative LUTS to ED. Another possible explanation is that the impact of irritative LUTS on ED may have a psychological origin as a consequence of increased stress and anxiety that accompanies severe urinary symptoms [29]. Owing to lack of functional and expressive investigations, this present study cannot provide further evidence for possible mechanisms that irritative LUTS influence the prevalence of ED. Nevertheless, considering the close relationship among NO/NOS-mediated pathway, ED and lower urinary tract, this pathway is considered to play a role on the causes of irritative LUTS and ED. NO has been suggested to be involved in the micturition process, namely by modulating bladder afferent nerves and related-reflex pathways in the spinal cord [22]. Filippi et al. demonstrate that PDE5 regulates bladder smooth muscle tone, strongly limiting the NO signalling, and that PDE5 inhibitor may be a possible therapeutic option for bladder dysfunction by ameliorating irritative LUTS [30].

There are two limitations in our study. First, many vascular risk factor, such as DM and hypertension, have no significant impact on ED in this study. These results are apparently different from other reports. We think insufficient subjects and ethnic group would be two major factors that make these vascular risk factors (DM and hypertension) having significant correlations to ED only in univariate analysis but not in logistic regression analyses. To elucidate these potential relationships, further more large-scale prospective studies are clearly needed. Second, subjects could not assess correctly the frequency, intermittency or strength (weakness) of the urinary stream. So, IPSS itself seems to be inadequate enough to estimate the condition of urination accurately. In the investigations of correlation between ED and LUTS, 24-h voiding diary and uroflowmetry are needed to properly assess the urinary symptoms.

In conclusion, our results indicate that age and LUTS are the most two independent risk factors for ED. Aging Taiwanese males with LUTS are at growing risk for ED, especially for those with significant irritative symptoms. As a result, it is important for clinicians to not only evaluate LUTS in patients with ED but also consider possible ED in men who seek treatment for LUTS, especially in those with relatively higher irritative score.

Acknowledgements

This study was sponsored by Taiwan National Science Council (NSC 97-2314-B-037-031) and Kaohsiung Medical University Hospital (KMUH 96 -6G 27; KMUH 96-6G 29; KMUH 97-7R 23). The authors sincerely acknowledge Ms. Chao-Shih Chen and Hsiung Hsu for their assistance in conducting health screening.