Abstract
This study aimed to evaluate the influence of the lifestyle, prostate volume (PV), and metabolic syndrome (MS) on lower urinary tract symptoms (LUTS) in the elderly males. A total of 764 men aged greater than 40 years were enrolled. Their severities of LUTS were assessed by the International Prostate Symptom Score questionnaire, while their MS was diagnosed according to the criteria developed by the National Cholesterol Education Program Adult Treatment Panel III. Lifestyle factors, PV, and components of MS were compared between no/mild and moderate/severe LUTS groups. In univariate analysis, age, cigarette smoking, alcohol consumption, physical activity, and PV significantly correlated with the severity of LUTS, but the presence or any components of MS did not. Results of multivariate analysis showed that aging, cigarette smoking, lack of regular exercise, and larger PV were independent predictors for moderate/severe LUTS. Notably, the risk factors for LUTS was influenced by the presence of MS. PV may play a role in determining the severity of LUTS for men without MS, while physical activity was the critical factor for men with MS. It was suggested that healthy lifestyle would be beneficial to lessen the severity of LUTS in the elderly males.
Introduction
Lower urinary tract symptoms (LUTS) are common complaints among the elderly males. The prevalence of LUTS was reported of 15–60% in men aged ≥40 years, increasing to 90% in men ≥80 years [Citation1,Citation2]. With a definition of greater than 7 points in the International Prostate Symptom Score (IPSS), the incidence of LUTS was as high as 42% in men aged ≥50 years in the primary health center [Citation3]. In addition to the physical discomfort, LUTS were also associated with depressive symptoms [Citation4]. The bothersome nature of LUTS leads to a decrease in the quality of life (QoL) and has significant socio-economical damage. Identification of the risk factors associated with LUTS would be useful for the prevention and treatment for LUTS.
Generally, LUTS are regarded as a hallmark of men suffering from benign prostatic hyperplasia (BPH). The BPH/LUTS complex appears to have enlarged prostate resulting in impingement on urethra and enhanced prostatic smooth muscle tone mediated by sympathetic nervous system [Citation5]. Although LUTS are closely correlated with BPH in the elderly males, the etiology of these symptoms remains unclear. Traditionally, the pathogenesis of BPH/LUTS complex has been focused on the age, genetic and hormonal factors. While these inevitable factors are important contributors, modifiable lifestyle factors including physical activity [Citation6,Citation7], smoking [Citation8,Citation9], and alcohol consumption [Citation9,Citation10] have been also considered to be related to BPH/LUTS complex.
Metabolic syndrome (MS), assumed to be related to unhealthy lifestyle, is a cluster of vascular risk factors that are associated with cardiovascular disease and type II diabetes. The prevalence of MS in the elderly is 27% in India, nearly 30% in Europe, more than 40% in the US [Citation11], and is expected to rise further as populations lead sedentary lifestyles. Men presenting the components of MS had significantly larger prostate volumes (PV) and enhanced sympathetic tone, which could result in increased LUTS [Citation12–16]. However, the correlation between MS and LUTS was controversial [Citation13,Citation17–19]. The purpose of this study was to determine the influence of MS and its components, lifestyle, and PV on LUTS in elderly males. Based on the potential interaction of these factors, we also examined the effect of lifestyle and PV on LUTS in men with and without MS. For the first time, we found that MS had an impact on predictors of LUTS.
Methods
From March 2008 to August 2009, our institution held free health screenings for males who lived in Kaohsiung city and were older than 40 years. All participants were volunteers and signed an informed consent that stated information about the study objectives. Ethics approval was authorized by the Institutional Review Board of Kaohsiung Medical University Hospital. Males were not included if they had medication influencing LUTS (α blockers, 5α-reductase inhibitors, anticholinergics, diuretics), flattened flow pattern in uroflowmetry suggesting urethral stricture, and did not provide individual’s complete information. Subjects were also excluded from analysis if they had a documented history or clinical symptoms of prostatitis, prostate cancer, urethral stricture, and neurologic diseases.
A total of 764 males were enrolled in the current study. All of the men completed a questionnaire during the interview and provided information about their demographic data, lifestyle factors, and complete medical, surgical and medicine histories. Subjects were defined as smokers or alcohol drinkers if they had regularly smoked 10 or more cigarettes per week, or had regularly consumed any alcoholic beverage one or more times per week, for at least one year. If subjects stopped smoking cigarette or drinking alcohol for at least 6 months, they were defined as former users. Regular physical activity was defined by a validated measure as doing sweated exercise for over half hour at least once per week [Citation20]. Detailed physical examinations including blood pressure (BP) were also performed for each subject. Body mass index (BMI) was calculated by the measured body weight and height, and the waist circumference (WC) was measured at the level of the umbilicus while the subject breathed normally. Hip circumference was recorded at the widest part of buttock and waist-to-hip ratio (WHR) was counted. Maximal flow rate was recorded in uroflowmetry and post-void residual urine was measured by ultrasonography. PV was measured by transrectal ultrasonography (TRUS) in only 32 cases due to discomfort of the procedure. Alternatively, PV was calculated by ellipsoid formula with prostate dimensions measured by suprapubic ultrasonography [Citation21], which was rapid, convenient, reliable, and free from suffering in the setting of health screenings.
Fasting blood samples were drawn for biochemical analysis. According to the consensus report of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) [Citation22], Asian male is diagnosed as MS if he had at least three of the following criteria: abdominal obesity (WC ≥90 cm), hypertension (BP ≥130/85 mmHg or on medication), increased fasting blood glucose (FBG ≥100 mg/dL or on medication), hypertriglyceridemia (triglyceride ≥150 mg/dL or on medication), and reduced high density lipoprotein cholesterol (HDL <40 mg/dL or on medication). The IPSS and QoL scores were used to assess LUTS [Citation23]. Scoring of IPSS allowed classification of each patient with no (0), mild (1–7), moderate (8–19) and severe (20–35) LUTS. Voiding symptom (VS) and storage symptom (SS) scores were also recorded and classified into different severities with the cut points proportional to those for LUTS.
Results were presented as mean ± standard deviation and median. We divided subjects into no/mild (IPSS = 0–7) and moderate/severe (IPSS = 8–35) LUTS groups because men with bothersome moderate-to-severe symptoms should be considered for active treatment [Citation23]. Subjects were also separated into no/mild and moderate/severe VS groups (VS score = 0–4 vs. 5–20) and SS groups (SS score = 0–3 vs. 4–15) for analysis. The chi-square test and independent Student’s t test were used to detect the differences in the frequencies and values of the above-mentioned clinical variables between the two groups. Crude odds ratios (OR) and the corresponding 95% confidence intervals (CI) were also calculated. Significant risk factors in univariate analysis were incorporated into multivariate analysis. Multiple logistic regression models were used to determine the independent factors which influence the severity of LUTS. All significance levels were set at α = 0.05 with a two-tailed hypothesis.
Results
The mean (median) age of the current participants was 56.5 ± 6.3 (56) years. The mean PV was 25.6 ± 13.1 (23.3) mL, with an average IPSS of 9.6 ± 7.0 (8) and QoL score of 2.5 ± 1.3 (2). MS was diagnosed in 25% of the participants (n = 191) in accordance with the NCEP ATP III criteria. All subjects were then divided into two groups, namely no/mild (n = 14 + 343, a total of 357) and moderate/severe (n = 322 + 85, a total of 407) LUTS groups, according to their severities of LUTS determined by the IPSS. We also separated subjects into two VS and SS groups according to their IPSS subscores.
Comparisons between groups showed that there were no significant differences in BMI, WHR, WC, FBG, HDL, triglyceride and the percentage of hypertension and MS (). However, compared with the no/mild LUTS group, males with moderate/severe LUTS were significantly older (57.3 ± 6.8 years vs. 55.7 ± 5.7 years; p = 0.001) and had larger prostate (27.2 ± 15.1 mL vs. 23.8 ± 10.2 mL; p < 0.001). Lifestyle factors including cigarette smoking (p < 0.001), alcohol drinking (p = 0.02), and regular physical activity (p = 0.03) were significantly different between these two groups. The differences of these parameters were also significant between the two VS and SS groups ().
Table I. Clinical characteristics of the males with no/mild LUTS and with moderate/severe LUTS.
Crude ORs and multivariate-adjusted ORs for moderate/severe LUTS were examined by logistic regression models (). Former smokers (adjusted OR = 2.17, 95% CI = 1.37–3.42) and current smokers (adjusted OR = 2.51, 95% CI = 1.54-4.10) had more than twice risks of suffering from moderate/severe LUTS than non-smoker. Aging and larger PV were identified as the independent risk factors for moderate/severe LUTS, while regular physical activity was beneficial to decrease a 28% risk of experiencing moderate/severe LUTS (adjusted OR = 0.72, 95% CI = 0.52–0.99). Similar results were also shown in different VS and SS groups (). Alcohol consumption including former and current drinkers did not significantly influence the risk of moderate/severe LUTS or VS. However, former drinker had a higher risk of moderate/severe SS.
Table II. Crude and multivariate-adjusted ORs (95% CI) of the age, lifestyle factors, and prostate volume for moderate-to-severe LUTS.
In order to understand the influence and adjust the confounding effect of MS, the current subjects were also divided into two groups, namely MS and non-MS groups. There was no significant difference in severity of the LUTS between these two groups (IPSS of MS and non-MS = 9.8 ± 7.2 and 9.6 ± 6.9, p = 0.7). However, MS was significantly associated with age, BMI, WHR, and the percentage of coronary artery disease (data not shown), and different independent factors in determining the LUTS were detected in men with and without MS (). Larger PV was significantly associated with LUTS only in men without MS (p = 0.018), while regular physical activity had protective effect only in men with MS (adjusted OR = 0.41, 95% CI = 0.21–0.83, p = 0.013). Cigarette smoking was significantly associated with LUTS in males regardless of MS ().
Table III. Multivariate-adjusted ORs (95% CI) of the age, lifestyle factors, and prostate volume for moderate-to-severe LUTS in subjects without metabolic syndrome (Non-MS group) and with metabolic syndrome (MS group).
Discussion
The development of LUTS results from the complex interrelation between the detrusor function, prostate size, and urethral resistance. BPH has been studied epidemiologically as a frequent cause of LUTS. We excluded cases with a medical history of neurologic diseases or urethral stricture aiming to decrease their confounding effect. Nonetheless, LUTS might be in response to multiple underlying abnormalities, such as overactive bladder, weak detrusor contractility, greater prostatic mass which is influenced by androgens and leads to impingement on the urethra (static component), and increased tone of prostatic smooth muscle which is governed by sympathetic nervous system (dynamic component) [Citation5]. Several epidemiologic surveys of different populations have been conducted to identify the risk factors for male LUTS, such as metabolic factors and lifestyle-related diseases [Citation6–16]. However, the potential risk factors determined in these previous studies were still conflicting. One possible reason for this discrepancy is the lack of a standard for the case definition. To minimize the inconsistency of these definitions, this study used LUTS, graded by universally accepted IPSS rather than BPH as the outcome measurement.
Male LUTS were multifactorial and aging was an important risk factor. Overactive bladder prevalence in Asian males was around 30% and increased with age [Citation24]. Similarly, detrusor underactivity was regarded as part of normative aging [Citation25]. In the subgroup analysis, we found the effect of aging was more pronounced in voiding symptoms. However, since we did not performed cystometrogram, we could not clarify if the result is related to aging-related weak detrusor contractility.
Conflicting data of the impact of cigarette smoking on LUTS were found. In our study, both current and former smokers were at increased risk for moderate-to-severe LUTS. Compared with non-smokers, current and former smokers had multivariate-adjusted ORs of 2.51 (95% CI: 1.54–4.10) and 2.17 (95% CI: 1.37–3.42), respectively. The positive correlation of LUTS with smoking might be suggested an expression of a tissue reaction to smoking-derived irritants. The plasma steroid hormone levels were affected by smoking and dihydrotestosterone accumulation due to nicotine has been found in the prostate of the dog [Citation26], which would be associated with prostatic enlargement. A great number of studies have reported that sympathetic overactivity was associated with chronic exposure to tobacco and nicotine, which might further affect prostatic tone. According to our results, ceasing smoking for half year seemed to be not enough to acquire benefit on LUTS. However, stopping smoking for a longer period is still promising because the long-term response to the smoking cessation appeared to reduce sympathetic bias [Citation27].
Alcohol consumption has been reported to be associated with BPH/LUTS. It may induce diuresis and aggravate bladder storage problems. In a meta-analysis executed by Parsons and Im, a decreased likelihood of BPH was found in men who drank daily [Citation10]. However, a trend toward increased risk of LUTS was also shown with increased alcohol intake [Citation10].
Physical activity has been indicated to be associated with a lower risk of moderate to severe LUTS. Prospective US cohort studies had found that men who walked 2–3 hours weekly or exercised at least once per week were at lower risk of high-moderate or severe LUTS (IPSS ≥15) and had a decrease of 25% in the risk of receiving surgical treatment for BPH compared with those who did not [Citation7,Citation28]. These findings were consistent with the results of a recent meta-analysis that the risk of LUTS could be reduced by moderate-to-vigorous physical activity after adjusting for several confounders [Citation6]. It hypothesized that reducing systemic sympathetic activity at rest by regular exercise would also decrease prostatic smooth muscle tone and thus alleviate LUTS.
BPH and the corresponding LUTS might be caused by sympathetic bias as an independent etiology of aging and hormone dysfunction. In human studies, Meigs et al indicated that symptomatic BPH were more likely to increase sympathetic activity [Citation29]. Another study reported that LUTS and subjective voiding complaints could be resulted from sympathetic hyperactivity [Citation30]. Subjects with MS have been found to have an unbalanced loss of autonomic neurons, resulting in predominance of the sympathetic nervous system [Citation31]. Therefore, the autonomic nervous system dysfunction may play a role in the correlation between the LUTS and MS [Citation13]. However, similar to our results, several studies have suggested that LUTS was not associated with the presence of MS [Citation17–19]. Nevertheless, we found regular exercise can improve LUTS in men with MS, which was assumed by normalization of their sympathovagal imbalance from MS. On the contrary, the elderly men without MS might have a lesser extent of sympathetic bias and could not reduce LUTS through regular physical activity.
Although there was a limited association between the size of prostate and LUTS [Citation32], their correlation was rarely studied according to the presence of MS. In addition, reducing prostate size by 5α-reductase inhibitor is clinically useful for relieving LUTS secondary to BPH. Furthermore, subjects presenting the components of MS and type II diabetes mellitus were found to have an enlarged prostate and increased LUTS [Citation12–16]. Owing to these evidences, the PV might be included in the analysis for risk factors of LUTS. Not in the elderly males with MS, our results have supported that the PV was significantly correlated with the severity of LUTS in those without MS. These subjects may not have sympathetic overactivity, that is, less extent of dynamic component resulted from MS. Accordingly, the prostatic enlargement (static component) may play a role in the development of LUTS. However, while PV was statistically significant in our analysis, it may still lack clinical significance due to the small difference between no/mild and moderate/severe LUTS groups and similar ORs in men with and without MS.
One of the strength of our study was that the inclusion of clinical measurements of prostate size for analysis, which was rarely found in previous studies. It has been demonstrated that digital rectal examination (DRE) was not as reliable as TRUS for measuring PV [Citation33]. However, a great majority of participants were unwilling to undergo TRUS in the free health examination. Consequently, we performed suprapubic ultrasonography, which was considered to be a more reliable alternative for precise measurement of PV than DRE [Citation21]. In subjects who underwent transrectal and suprapubic ultrasonography, the correlation in measurement of PV was high (r > 0.9). One limitation of our study was that our subjects were all volunteers who were recruited from the community. Therefore, there was a bias in subject selection. Second, we did not include other lifestyle-related factors, such as daily fluid intake and sleep quality in our analysis. Third, our observation could be resulted from racial differences between the Asian and the West. Fourth, cross-sectional study was not sufficient to determine a causal relationship between these factors and LUTS, and a prospective study is needed in the future.
Males who are older, smokers, and lack of physical activity are at higher risk of moderate/severe LUTS. MS may not have a direct effect on LUTS, but the prostate size should be considered for LUTS in men without MS. The potential correlation of LUTS with lifestyle factors suggests that regular physical exercise and swearing off tobacco are beneficial for reducing LUTS. Further studies are needed to determine whether lifestyle interventions would alter the progression of LUTS.
Acknowledgments
This study was supported by grants from Taiwan National Science Council (NSC 98-2314-B-037-030-MY3; NSC 99-2314-B-037-022-MY3), Kaohsiung Medical University Hospital (KMUH 99-9R12; KMUH 99-9R13; KMUH 99-9R14; KMUH 100-0R42) and partly by 97-CCH-KMUH-001. Special thanks the assistance from the Statistical Analysis Laboratory, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University.
Declaration of Interest: The authors report no conflicts of interest.
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