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- Original Article -
Are age, anthropometry and components of metabolic
syndrome-risk factors interrelated with lower urinary tract
symptoms in patients with erectile dysfunction? A prospective study
Jae-Seung Paick1, Ji-Hyun Yang1, Soo-Woong Kim1, Ja-Hyeon Ku2
1Department of Urology, Seoul National University College of Medicine, Seoul 111744, Korea
2Department of Urology, Seoul Veterans Hospital, Seoul 134791, Korea
Abstract
Aim: To evaluate the effects of metabolic profiles on lower urinary tract symptoms (LUTS) in men with erectile
dysfunction (ED). Methods: A total of 75 impotent men aged 25_75 years old (mean 58.1 years) were included in
the study on a prospective basis. Patients were evaluated with a complete history, physical examination,
anthropometry and metabolic profiles. LUTS were assessed using the International Prostate Symptom Score (IPSS).
Results: Overall, there was no correlation between the IPSS and continuous parameters. However, when continuous variables
were categorized, some parameters were significantly associated with LUTS. Patients with triglyceride level of
150 mg/dL or higher had more severe symptoms than those with tiglyceride levels less than 150 mg/dL
(19.4 ± 2.4 vs.
14.3 ± 1.1, P = 0.033). When 40 mg/dL was chosen as the high-density lipoprotein (HDL)-cholesterol cut-off
level, the IPSS was significantly different between the two groups divided by 40 mg/dL
(19.4 ± 2.6 for HDL-cholesterol < 40 mg/dL
vs. 14.4 ± 1.0 for HDL-cholesterol
¡Ý 40 mg/dL, P = 0.042). The area under the receiver operating
characteristic curve (AUROCC) of triglyceride was 65.7% (95% confidence interval [CI], 52.6%_82.3%;
P = 0.034) for severe LUTS. However, the AUROCC for 'HDL-cholesterol' was not significant (area, 65.4%; 95% CI,
48.2%_82.7%; P = 0.062). No other factors were determined to be significant in this regard.
Conclusion: The results of the present study indicate that some metabolic profiles might influence LUTS in men with
ED. (Asian J Androl 2007 Mar; 9: 213_220)
Keywords: lower urinary tract symptoms; erectile dysfunction; metabolic syndrome; body mass index; testosterone
Correspondence to: Dr Ja-Hyeon Ku, Department of Urology, Seoul Veterans Hospital, 6-2, Doonchon Dong, Kangdong Ku, Seoul
134791, Korea.
Tel: +82-2-2225-1392 Fax: +82-2-483-4260
E-mail: randyku@hanmail.net
Received 2006-02-06 Accepted 2006-06-14
DOI: 10.1111/j.1745-7262.2007.00211.x
1 Introduction
According to National Cholesterol Education Program, a patient with metabolic syndrome has three
or more risk factors consisting of the disorder of lipid
storage, insulin resistance and hypertension [1]. Esposito
et al. [2] reported that compared with age- and
weight-matched control subjects, patients with metabolic
syndrome had increased prevalence of erectile dysfunction
(ED); moreover, there was an increase in prevalence of
ED as the number of components of metabolic syndrome
increased, suggesting that the cumulative burden of
cardiovascular risk might be central to the pathogenesis of
ED. Conversely, ED can be considered a risk marker of
metabolic syndrome and its associated conditions [3, 4].
Both lower urinary tract symptoms (LUTS) and ED
are common within a similar gender and age distribution
in older men, but there is little evidence to support a link
between LUTS and ED. However, many community-based studies reported a statistically significant
association between LUTS and ED [5_11]. Furthermore,
recent studies suggested that benign prostate hyperplasia
(BPH) is a component of the metabolic syndrome and
that BPH patients might share the same metabolic
abnormality with patients of metabolic syndrome [12_14]. In
addition, Poulakis et al. [15] reported that risk factors
for the occurrence of postoperative, newly reported ED
were diabetes and intraoperative capsular perforation.
Therefore, we suspected that metabolic profiles might
affect LUTS of impotent men. To our knowledge, however, it is unknown which profiles impact LUTS in
patients suffering from ED because previously such
effects on LUTS have not been systemically investigated.
The present study was designed to evaluate the effects
of metabolic profiles on LUTS in men with ED.
2 Materials and methods
2.1 Patients
ED patients admitted urology outpatient clinic
between January and December 2004 were recruited.
Patients who were eligible and willing to participate in the
study were assessed. The eligibility criteria included:
aged 20 years or older and married with a stable and
heterosexual relationship in at least the past 6 months.
The exclusion criteria of this study included the use of
medications for the control of bladder symptoms,
bladder tumors, bladder stones, urethral strictures,
neurogenic bladder dysfunction and restricted mobility.
Patients were also excluded from the analysis if they had a
documented history or clinical symptoms of prostatitis,
prostate cancer, or prostatic intraepithelial neoplasia on
biopsy, serum prostate-specific antigen (PSA) levels in
excess of 20 ng/mL, history of prostate surgery or
radiotherapy, acute urinary retention or an indwelling
catheter, evidence of acute urinary infection
(pyuria and bacteriuria) on urinalysis, or if they had ever taken
5α-reductase inhibitors. A total of 75 men of 25_75 years
old (mean age 58.1 years) were included in the study on
a prospective basis.
2.2 Methods
At the initial visit, patients' complete medical history
was evaluated, with a physical examination consisting of
digital rectal examination and standard blood test,
including serum PSA, serum fasting glucose level and lipid
profiles, such as concentrations of total cholesterol,
high-density lipoprotein (HDL)-cholesterol, low-density
lipoprotein (LDL)-cholesterol and triglyceride. Patients of 50 years
or older with suspicious results of digital rectal
examination and/or elevated PSA levels in excess of 4 ng/mL
also underwent systemic sextant biopsies under transrectal
ultrasonographic guidance, using an 18-gauge needle
fitted to an automatic biopsy gun. Hypoechoic lesions
detected on ultrasonography and areas corresponding to
palpable abnormalities on digital rectal examinations were
also biopsied. Blood samples were separated, and then
frozen at _80ºC until used for analysis. The body size of
patients, including height and body weight, was
determined using an automatic instrument. The body mass
index (BMI) of each patient was calculated as the body
weight in kilograms divided by the square of the height
in meters. Information on demographic characteristics
was collected by questionnaire. LUTS and symptom-specific quality of life were assessed using the
International Prostate Symptom Score (IPSS) and the IPSS
quality of life scores. ED was defined as a consistent
inability to achieve or maintain penile erection sufficient
for satisfactory sexual performance. Documented
evidence of ED included a medical history of at least
6-month duration, physician records and objective testing,
if available. Baseline sexual function was also evaluated
using the self-administered International Index of
Erectile Function (IIFE) [16]. The severity of ED was
confirmed on the six-item erectile function domain (Erectile
Function domain score 6_25) [17].
2.3 Statistical analysis
Data are presented as mean ± SE or percentages,
according to the variables. Correlations among
continuous variables (age, anthropometry and blood tests) and
the IPSS were determined using the Pearson correlation
test. Statistical comparisons of continuous data were
performed using paired t-test or one-way analysis of
variance (ANOVA) and the Armitage test for categorical data.
We assessed whether clinical parameters, including age,
anthropometry and metabolic profiles, are discriminative
for severe LUTS (IPSS = 20) using the area under the
receiver operating characteristic curve (AUROCC). The
area under the curve is a suitable parameter to
summarize the overall discriminative or diagnostic value of a
model and can range from 0.5 (flipping a coin, a useless
model) to 1.0 (perfect discrimination). The larger the
AUROCC approached 100% (i.e. the more the receiver
operating characteristic [ROC] curve approached the
upper-left corner), the greater the predictive power. The
level of statistical significance was defined as
P < 0.05 and all statistical tests were two-sided. Statistical
analyses were performed using a commercially available
analysis program, SPSS version 10.0 (SPSS, Chicago, IL,
USA).
3 Results
The mean age of the studied patients was 58.1 years,
and their mean PSA level was 1.6 ng/mL. All the
patients enrolled in this study had ED (IIEF-EF domain
score 6_25). Basic characteristics of patients are shown
in Table 1. The results of Pearson's correlation analysis
in 75 studied patients with ED are summarized in Table 2.
Overall, there was no correlation between IPSS scores
and continuous parameters. When continuous variables
were categorized, some parameters were significantly
associated with LUTS. Patients with triglyceride levels
of 150 mg/dL or higher had more severe symptoms than
those with triglyceride levels of less than 150 mg/dL
(19.4 ± 2.4 vs. 14.3 ± 1.1,
P = 0.033). When 40 mg/dL was chosen as the HDL-cholesterol cut-off level, the IPSS
were significantly different between the two groups
divided by this level (19.4 ± 2.6 for HDL-cholesterol
< 40 mg/dL vs. 14.4 ± 1.0 for HDL-cholesterol
³ 40 mg/dL, P = 0.042) (Table 3).
Figure 1 presents the area under the receiver operating characteristic curves for the
discriminative value of clinical parameters on severe
LUTS. The AUROCC of triglyceride was 65.7% (95% CI, 52.6%_82.3%;
P = 0.034) for severe LUTS. However,
the area under the receiver operating characteristics curve
for "HDL-cholesterol" was not significant (area,
65.4%; 95% CI, 48.2%_82.7%; P = 0.062) (data not shown). No
other factors were determined to be significant in this
regard (data not shown). The performance of sensitivity and
specificity at various triglyceride levels are shown in Table 4.
Using the standard cut-off of 150 mg/dL, sensitivity of
44.4% and specificity of 85.0% were observed.
4 Discussion
With the growing life expectancy and absolute
number of the elderly, studies on age-related diseases are
becoming increasingly important. Therefore, the
association between LUTS and sexual dysfunction has been
investigated. In 2 011 French men aged 50_80 years,
Macfarlane et al. [5] found that the probability of sexual
dissatisfaction increased with the severity of LUTS.
Among 423 British men aged 40 years or older, Frankel
et al. [6] observed that sexual dysfunction was
associated with a wide range of LUTS. Terai
et al. [18] also reported that ED is highly prevalent among Japanese men
with LUTS and is significantly associated with the
severity of LUTS after controlling for age. Several other
community-based studies using the IPSS and various male
sexuality questionnaires showed that a moderate to
severe IPSS is significantly associated with ED, with
reported age-adjusted odds ratios (OR) of 2.11 [7], 1.8_7.5
[8], 1.39 [9], 2.25 [10] and 2.05_5.75 [11], depending
on the severity of IPSS.
Therefore, ED and LUTS might have a common
causa-tive factor. Although the mechanism underlying the
relationship between lower urinary tract function and ED
remains unknown, four leading theories of how these
diseases interrelated are suggested: the nitric oxide (NO)
synthase/NO [19], autonomic hyperactivity effects on
LUTS and ED [20], increased Rho-kinase activation/downregulation of endothelin-B receptor sites [21], and
prostate and penile atherosclerosis [22]. However, it is
unclear whether sexual dysfunction in older men is
causally related to BPH or only a consequence of aging.
Blanker et al. [8] revealed that urinary flow rate and
prostate enlargement have no independent influence on ED.
Green et al. [23] also showed that ED is not associated
with prostate volume or maximal flow rate.
ED is more prevalent in men with metabolic syndrome [2]. Metabolic syndrome represents a
constellation of risk factors for cardiovascular disease. Strong
epidemiological evidence links the subsequent risk of ED
to the presence of well-recognized risk factors for
coronary disease, such as increased body weight, diabetes,
cardiovascular disease, hypertension and dyslipidemia
[24_26]. All the major risk factors for cardiovascular
disease are associated with increased production of
superoxide radicals and other reactive oxygen species
(ROS), which, in turn, decrease NO bioavailability [27].
Abnormalities of this vasodilator system play an
important role in the pathophysiology of ED, as it is now
recognized that vascular disease of the penile arteries is
the most common cause of ED, accounting for up to 80% of cases [28].
Therefore, the earliest events in the development of atherosclerosis (endothelial dysfunction)
are similar to the earliest events in the development of ED.
Recently, several investigators have examined the
association of components of the metabolic syndrome
with BPH. Previous studies
[12_
14] demonstrated that the prostate gland volume is related to components of
the metabolic syndrome, including non-insulin-dependent
diabetes mellitus, hypertension, obesity, low
HDL-cholesterol levels and high insulin levels. These findings
suggested that metabolic profiles constitute risk factors for
the development of BPH and generate a hypothesis of a
causal relationship between metabolic profiles and the
development of BPH and of an increased sympathetic
nerve activity in men with BPH. Furthermore, in the Third
National Health and Nutrition Examination Survey [29],
history of diabetes (OR, 1.67; 95% CI, 0.72 to 3.86) and
hypertension (OR, 1.76; 95% CI, 1.20 to 2.59) was
positively associated with LUTS and men classified as
having three or more components of the metabolic syndrome
had increased odds of LUTS (OR, 1.80; 95% CI, 1.11 to
2.94). These findings support the role for metabolic
perturbations in the etiology of LUTS.
The main aim of this study was to evaluate the role
of metabolic profiles in LUTS in patients with ED. In
our study, some metabolic parameters, such as
triglyceride and HDL-cholesterol levels, were associated with
LUTS and were the discriminative factors for severe
LUTS. To our knowledge, this finding has not been
described previously. The pathophysiological
mechanisms remain unclear, but there are several possible
explanations for our results. Men with low
HDL-cholesterol levels have a larger prostate gland than those
without this condition [12] and men with fast-growing
prostate glands had lower HDL-cholesterol levels than those
with slow-growing prostate glands [13, 14]. In a
recent study, serum triglycerides emerged as the main
determinants of prostate gland volume in subjects with
prostate hypertrophy [30]. Furthermore, Lee
et al. [31] reported that the serum level of HDL-cholesterol
showed a biphasic association with moderate to severe LUTS. In a rabbit model, hypercholesterolemia
resulted in thickening and fibrosis of the prostate,
changing its mechanical properties, and also impaired
neurogenic relaxation in the prostate, although to a lesser extent
than chronic ischemia [32]. In addition, the effects of
impaired lipid metabolism on the contractile and relaxation
response of smooth muscles or smooth muscle cell
degeneration are well known [33, 34]. However, because
these studies were performed on subjects without sexual
dysfunction, further research is needed to clarify the
underlying mechanisms involved.
Limitations affecting our current findings must be
considered. First, our study included only Korean men.
The population within each country differs culturally and
sociodemographically. The results of studies of urinary
symptoms in specific countries might not be generally
applicable in other countries, because different countries
have different cultural backgrounds and specific
health-care delivery systems [35]. Second, using
cross-sectional methods might not allow definitive conclusions
about the causal link between the severity of ED and the
investigated variables. In addition, our study was not a
community-based study. Data from general practice
settings might have been preferable, although other
biases might also present in these populations (e.g. the
volunteer bias). In the absence of general practice data,
the results from clinical trials were used as the next best
available information. Third, because this was a pilot
study, the sample size was small. In our study, although
a trend of influence of some metabolic profiles on LUTS
was observed, no statistical significance was observed.
The lack of statistical significance might be a result of
the relatively small number of patients. Therefore,
further study with larger sample size is necessary. Finally,
the study did not include all demographic variables.
Because other sociodemographic and health status variables,
such as marital status and work situation, might affect
urinary symptoms, additional studies including these
variables are needed. Also, some factors that could be
important causes of severe LUTS have not been included
in this study.
In this study, we found that some metabolic profiles
in patients with ED might influence LUTS. These
findings suggest that early detection or correction of these
metabolic profiles might reduce the prevalence of LUTS
in men with ED. However, although our study provides
some descriptive information on LUTS in patients
suffering from ED, the findings need to be confirmed in
larger epidemiological studies.
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