Abstract
Background. Few prospective studies have been conducted to identify risk factors associated with lower urinary tract symptoms (LUTS). Our objective is to evaluate the dietary, lifestyle and medical risk factors of LUTS.
Methods. Data were collected from a large prospective cohort of elderly Chinese men in Hong Kong. Eight hundred seventy-one subjects provided response to a structured interviewer-administered questionnaire and physical examination at baseline and at 4-year follow-up. LUTS and depressive symptoms were assessed using International Prostate Symptom Score (IPSS) and Geriatric Depressive Symptom Scale (GDS).
Results. The GDS score was independently associated with increased risk of having moderate to severe LUTS (odd ratios (OR) = 2.08; confidence interval (CI) = 1.28–3.40; Wald chi-square test = 9.52 and p = 0.023). A history of coronary heart disease was independently associated with increased risk of moderate to severe LUTS (OR = 1.65, CI: 1.05–2.59; Wald chi-square test = 4.74 and p = 0.029). Alcohol consumption of seven drinks or more per week was independently associated with increased risk of moderate to severe LUTS (OR = 2.51; CI: 1.32–4.79; Wald chi-square test = 8.01 and p = 0.018).
Limitations. We have studied LUTS but not surgical BPH.
Conclusions. The results showed that medical and lifestyle factors may increase the risk of LUTS in Chinese elderly men.
Background
Previous studies have been conducted to evaluate the risk factors of lower urinary tract symptoms (LUTS) [Citation1–12]. Although these studies have identified a number of modifiable risk factors associated with LUTS [Citation1–3,Citation6,Citation7,Citation9–12], a few of these studies have used a prospective design [Citation8]. As a result, the temporal relationships between LUTS and these risk factors were often unknown. Recently, Kristal et al. [Citation13] conducted a study on the dietary risk factors for incident benign prostatic hyperplasia in a large cohort in Caucasians. However, dietary intake of isoflavone was not collected which may be an important protective factor for the occurrence of LUTS [Citation14]. We previously [Citation15] reported a reduction of risk for LUTS for those with a regular intake of dietary isoflavone using cross-sectional data. However, this study was cross-sectional and a temporal relationship could not be delineated. The current study was conducted to evaluate the dietary, lifestyle, and medical risk factors of LUTS in a prospective manner in Southern Chinese men.
Methods
Study subjects
Details of the current study were reported previously [Citation10–12,Citation15]. In brief, 2000 Chinese men aged 65 years and above were recruited and were followed for a total of 4 years. To be eligible, the subjects had to be able to walk independently, and the subjects were recruited with an aim to have around 33% of subjects in each of the following age groups: 65–69, 70–74, ≥75 years. The subjects were recruited by placing recruitment notices in housing estates and community centers for the elderly. For this analysis, men with a history of bladder or prostate cancer or surgery for bladder cancer, men who regularly took α-blockers and anti-androgen drugs were excluded, as these may mask and confound the presence of prostatic symptoms. Moreover, those with the presence of moderate to severe LUTS at baseline were also excluded as we were interested in risk factors associated with new development (incident) of LUTS at the end of the 4-year period. The study was approved by the ethics committee of the Faculty of Medicine, the Chinese University of Hong Kong.
Questionnaire
All information on independent variables in this study were collected at intake. Demographic and socio-economic information were collected that included age, place of origin, education levels, and occupation. Information on subjects' medical history was obtained based on subjects' self-reports of medical conditions. Participants were asked, ‘Has a doctor ever told you that you had or have a list of 14 types of medical conditions’ during their interviews. Moreover, they were separately being asked, ‘Has a doctor ever told you that you have cancer’ and questions were specifically directed at the presence of prostate cancer or other cancer surgery received for the cancers.
Dietary intake
Dietary intake was assessed by a modified version of the Block food frequency questionnaire, based on data obtained in the Hong Kong Adult dietary survey in 1995 [Citation16]. Two hundred eighty-five dietary items were included in the questionnaire. Mean nutrient quantitation per day was calculated using food tables derived from McCance and Widdowson [Citation17] and the Chinese Medical Sciences Institute [Citation18]. For the measurement of soy content, the questionnaire included 10 soy items commonly consumed by the Hong Kong Chinese population that included soy-bean, canned soybean, soft tofu, firm tofu, deep fried tofu, tofu-pop, bean curd skin, bean curd sheet, soy milk, and vitasoy (a common brand of soymilk consumed by the Hong Kong population). Isoflavone content in soy products was estimated based on the published data [Citation19,Citation20].
Lower urinary tract symptoms
The presence and severity of LUTS were assessed by the Chinese version of the International Prostatic Symptoms Score (I-PSS) [Citation8] for LUTS. These were collected at both baseline and at the end of 4 years. The I-PSS assesses nocturia, frequency, urgency, intermittency, weak stream, incomplete emptying and straining. Using standard cut-points for symptom severity [Citation21], men were defined as having severe LUTS if they scored 20 or more on the I-PSS. They were defined as having moderate LUTS if they scored from 8 to 19 and were defined as having mild LUTS if they scored 7 or less.
Cigarette smoking and alcohol consumption
Data on the duration and amount of past and current use of cigarettes, cigars, and pipes were obtained. Smoking status was defined as former smoker (at least 100 cigarettes smoked in a lifetime), current smoker, and those who never smoke. For current smokers, the number of cigarettes smoked per day over the previous 12 months was collected.
For alcohol consumption, subjects were asked to report their daily frequency of intake of alcohol and other beverages in portion sizes. They were also asked to report on how many days of the week they consumed alcohol. One standard drink was defined as 1 unit of alcohol which is equal to 10 g of alcohol. For beer, one standard drinks equals to 1 can of beer (330 ml) which is equivalent to 1 glass of wine (100 ml) which is equal to 1 shot of spirit or liquor (30 ml).
Physical activity
Physical activity was measured by the validated Physical Activity Scale for the Elderly Questionnaire (PASE) [Citation22]. It measured the level of physical activity in individuals aged 65 years and older. The instrument is a self-report/interview-based measure designed to capture and assess occupational, household, and leisure activities typically performed by older adults. This was adapted in Hong Kong Chinese men by adding activity items which were popular in the local culture [Citation23].
Clinically relevant depressive symptoms were diagnosed by face-to-face interviews, using a validated 15-item Chinese version of the Geriatric Depression Scale (GDS) [Citation24]. The use of the 15-item GDS was found to be a useful measure and screening tool for geriatric depression due to the elderly tendency to fatigue with long questionnaire [Citation25]. The GDS short form was found to be a highly reliable (reliability coefficient of 0.90) and valid screening device (sensitivity of 96.3% and 87.5 % specific) for assessing geriatric depression in Hong Kong [Citation24].
Physical examination
Body weight was measured, with subjects wearing a light gown, by the Physician Balance Beam Scale (Healthometer, IL). Height was measured by the Holtain Harpenden standiometer (Holtain Ltd, Crosswell, UK). Hip and waist were also measured and the ratio of hip to waist was determined.
Assessment of peripheral atherosclerosis
Ankle Brachial Index (ABI) was calculated and was used for the assessment of peripheral atherosclerosis. Resting pulse rate was measured twice with subjects in sitting position for 30 s, after at least 5 min of rest in a quiet room. The average pulse rate was obtained. Duplicate measures of supine blood pressure in right arm and both ankles were performed using a standard mercury sphygmomanometer and an 8-MHz Doppler probe. The study coordinator placed an appropriately sized cuff over the right brachial artery and around each ankle, proximal to the malleolus. For each subject, systolic pressure was measured in the right brachial artery first, then in the right lower extremity and left lower extremity. The ABI was calculated for each leg by dividing the posterior tibial systolic pressure in each lower extremity by the upper extremity pressure. The lowest ankle-arm index of the two was used to determine the extent of ischemic disease.
Statistical analysis
Crude odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated for examination of associations between putative lifestyle and medical factors at baseline and the presence of moderate to severe LUTS at the 4-year follow-up visit. Subjects with moderate to severe LUTS at baseline were excluded for this analysis such that only risk factors for new development of moderate to severe LUTS (incident LUTS) at the 4-year follow-up were analyzed. Putative lifestyle and medical factors were factors that have been shown to be related to LUTS in the literature. For continuous variables that included alcohol intake, GDS score, ABI, dietary intake of isoflavone, protein, fat, meat and vegetables, the variable was divided into tertiles or quartiles to investigate the relationship between these variables and severity of LUTS. This has to deal with possible non-linear relationships between the independent and dependent variables. Variables that had multiple categories were tested first in a Wald test to find out if there were any differences among the response categories to avoid type I error problem from multiple tests. Variables found to be associated with LUTS in the initial bivariate analyses were put into a multiple logistic regression model. All statistical analyses were performed using the statistical package SAS, version 8.02 (SAS Institute, Cary, NC).
Results
Clinical characteristics
Of the 2000 men recruited, 20 men were excluded as they had either history of bladder surgery or had history of bladder or prostate cancer. Two hundred forty-one men were excluded as they were current users of α-blockers or anti-androgen drugs for prostate problems. A further 665 men were excluded as they had moderate to severe LUTS at baseline. At the end of the 4-year follow-up, 201 men were lost to follow-up or refused to come back for interviews. Two men who were interviewed at 4-year follow-up refused to answer the questions on LUTS. As a result, complete data were collected and analyzed on 871 men. Their baseline demographic, socio-economic and medical factors are shown in .
Table I. Baseline demographic, socio-economic, and medical characteristics (n = 871).
Risk factors for lower urinary tract symptoms
Besides age, a number of lifestyle and medical factors were associated with moderate to severe LUTS at the initial bivariate analyses (). For lifestyle factor, consumption of more than seven drinks per week over the past 12 months was associated with increased risk of having moderate to severe LUTS (OR = 2.18; CI: 1.16–4.10; Wald chi-square test = 6.47; p = 0.039). Among medical factors, having a history of coronary heart disease was associated with an increased risk of having moderate to severe LUTS (OR = 1.68; CI: 1.08–2.61; Wald chi-square test = 5.34; p = 0.02). Having a GDS score of 4 and above was associated with increased risk of having LUTS (OR = 2.14; CI: 1.32–3.46; Wald chi-square test = 10.4; p = 0.02).
Table II. Crude odds ratios for having moderate to severe LUTS in relation to putative risk factors (n = 871).
After all lifestyle factors and medical factors that were shown to be significantly associated with having moderate to severe LUTS were entered into the multiple regression model, the association between increasing age and severity of LUTS persisted. In the multivariate logistic regression model, the association between having a history of cardiovascular disease, having consumption of seven standard drinks of alcohol per week in the past 12 months and having a GDS score of 4 and above were independently associated with increased risk of having moderate to severe LUTS ().
Table III. Adjusted odds ratios for having moderate to severe LUTS in relation to putative risk factors (n = 871).
Conclusions
To our knowledge, this is the first study in Asia that has evaluated a comprehensive list of risk factors, including depressive symptoms and dietary isoflavone on the development of moderate to severe LUTS in elderly men. Previous studies have been conducted to evaluate the relationship between LUTS and depressive symptoms [Citation10–12,Citation26–28] and have demonstrated a positive relationship. However, all studies that have been conducted up to date were cross-sectional and only one cross-sectional study has investigated the relationship between having depressive symptoms and the occurrence of LUTS [Citation29]. Although the relationship between LUTS and increased odds of having depressive symptoms could be understood as reflecting demoralization related to LUTS, the reason for the relationship between having depressive symptoms and the development of LUTS is less clear. Some authors suggested that this may be related to increased adrenergic tone that causes both depressive symptoms and urological symptoms [Citation27] or to the same neurotransmitter that leads to depression and urologic symptoms [Citation29,Citation30], while others suggested that genetic factors may account for the relationship involving the Phophodiesterase (PDE) isoenzymes, which are known to have a role in both LUTS and depressive symptoms [Citation10–12,Citation27,Citation31].
Contrary to our previous findings using cross-sectional data [Citation15], we failed to find an association between dietary intake of isoflavone and decreased risk of having LUTS. Furthermore, contrary to recently published results from a large prospective study in the US [Citation13], no associations were found between various dietary patterns and LUTS in this study. However, as we have excluded men with moderate to severe LUTS at baseline, and there was loss to follow-up in our study, the sample size is much smaller when compared to that of the previous cross-sectional study, which could have accounted for the negative findings. Moreover, our follow-up time is relatively short when compared to the study conducted in the US.
In our study, coronary heart disease was independently associated with subsequent LUTS. Adjustment with β-blockers or physical activity did not change the results. The association between increased risk of LUTS and heart diseases were demonstrated previously in Chinese [Citation10–12], Caucasians [Citation5] and African-Americans [Citation2]. However, few studies have evaluated this relationship using prospective data. Our results thus confirm this relationship and showed that self-reported cardiovascular disease could lead to the development of moderate to severe LUTS.
The relationship between alcohol consumption and LUTS has been evaluated in a number of cross-sectional studies but the findings were inconsistent. Alcohol consumption has been shown to be inversely related to surgically treated Benign Prostate Hyperplasia (BPH), clinically diagnosed BPH or severity of LUTS in some studies [Citation5,Citation7] while others demonstrated a positive relationship between heavy alcohol consumption and LUTS [Citation3]. In a recent prospective study, alcohol consumption was shown to be inversely related to benign prostate hyperplasia measured by either surgery or questionnaires. The reason for the discrepancy between results from this recent prospective study and our study is not known.
Although there are differences with the recall period with respect to various scales or questions used in assessing the presence of chronic conditions (ever been diagnosed), the presence of LUTS (last month) and depressive symptoms (last week), the fact that we have excluded those with the presence of moderate to severe LUTS at baseline and we have only investigated prospectively the ‘incidence’ of new cases of moderate to severe LUTS ensures the these pre-existing medical, lifestyle and psychological factors preceded the occurrence of moderate to severe LUTS at the end of follow-up.
Limitations
Potential limitations of this study have been discussed previously [Citation15]. This includes the fact that we have only studied LUTS but not surgical BPH or diagnosed BPH using other diagnostic instruments which would be more time consuming and invasive and less possible in a large study like ours. Moreover, we have only used a scale (IPSS) to collect information on LUTS. Since lower urinary tract also includes bladder, prostate and urethra, this scale is unlikely to collect the entire LUTS in men. Moreover, LUTS symptoms have been shown to exhibit progression and regression over time. As a result, the 1 month recall time frame of the IPSS questions could have confounded our results, although the exclusion of moderate to sever LUTS at baseline and the measurement of increased severity of LUTS over time and our large sample size will reduce the impact of this problem.
Another limitation is that our subjects were all volunteers recruited from the community and that they are all ambulatory which may mean they could be more health conscious. Analysis of our sample with those from a population survey in Hong Kong showed that our sample of elderly males were more educated with higher levels of health awareness which might have attracted them to participate in our study in the first place [Citation15]. However, this factor is unlikely to affect our results on risk factors associated with LUTS.
Furthermore, anyone with severe problems of LUTS may find it inconvenient to come to take part in this study which may create selection bias of presumably healthy subjects. As a result, we could have underestimated the prevalence of LUTS in our population, although such bias would unlikely affect our results in finding risk factors of LUTS. A third limitation is that we had used interviewers to collect information on IPSS. In the literatures, IPSS was usually self-administered. Potential limitation of this approach may include subjects being unwilling to disclose information that they found to be embarrassing or difficult to admit. However, as many elderly in Hong Kong are illiterate (60% of our subjects had primary education or lower), this may be the only feasible option in this study. Moreover, using this approach, only two subjects were unwilling to answer the questions on LUTS which made it unlikely that our results were affected. Fourth, for diagnosis of chronic medical conditions, only self-reported medical information was used to report the presence of hypertension, stroke, cardiovascular diseases, and diabetes, which is less accurate than chronic diseases defined by the use of blood tests or medical records. Lastly, we have only used a screening tool, the GDS to study depressive symptoms. We do not know if those with high GDS scores truly had a diagnosis of major depression, making it hard to develop insight of the underlying psychosomatic mechanism between major depression and LUTS.
We showed that both having depressive symptoms, the presence of cardiovascular diseases and an intake of more than seven drinks per week of alcohol were associated with the development of moderate to severe LUTS in Chinese elderly men. Although the development of LUTS is often considered as an inevitable part of aging, it appears that certain medical factors and alcohol drinking may exacerbate the problem. These observations provide further research directions on the potential benefits by modifying these risk factors in men who are at risk for LUTS.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- Gass R. Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. BJU Int 2002;90:649–654.
- Giovannucci E, Rimm EB, Chute CG, Kawachi I, Colditz GA, Stampfer MJ, Willett WC. Obesity and benign prostatic hyperplasia. Am J Epidemiol 1994;140:989–1002.
- Joseph MA, Harlow SD, Wei JT, Sarma AV, Dunn RL, Taylor JMG, James SA, Cooney KA, Doerr KM, Montie JE, Schottenfeld D. Risk factors for lower urinary tract symptoms in a population-based sample of African-American men. Am J Epidemol 2003;157:906–914.
- Lee E, Park MS, Shin C, Lee H, Yoo K, Kim Y, Shin Y, Paik HY, Lee C. A high-risk group for prostatism: a population-based epidemiological study in Korea. Br J Urol 1997;79:736–741.
- Meigs JB, Mohr B, Barry J, Collins MM, McKinlay JB. Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men. J Clin Epidemol 2001;54:935–944.
- Platz EA, Kawachi I, Rimm EB, Colditz GA, Stampfer MJ, Willett WC, Giovannucci E. Physical activity and benign prostatic hyperplasia. Arch Intern Med 1998;158:2349–2356.
- Platz EA, Rimm EB, Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Giovannucci E. Alcohol consumption, cigarette smoking, and risk of benign prostatic hyperplasia. Am J Epidemol 1999;149:106–115.
- Shiri R, Hakkinen J, Koskimaki J, Hakama M, Tammela TLJ, Auvinen A. Erectile dysfunction influences the subsequent incidence of lower urinary tract symptoms and bother. Int J Impot Res 2007;19:317–320.
- Suzuki S, Platz EA, Kawachi I, Willett WC, Giovannucci E. Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia. Am J Clin Nutr 2002;75:689–697.
- Wong ML, Whelan F, Deloukas P, Whittaker P, Delgado M, Cantor RM, McCann SM, Licinio J. Phosphodiesterace genes are associated with suspceptability to major depression and antidepressant treatment response. Proc Natl Acad Sci USA 2006;103:15124–15130.
- Wong SY, Hong A, Leung J, Kwok T, Leung PC, Woo J. Lower urinary tract symptoms and depressive symptoms in elderly men. J Affect Disord 2006;96:83–86.
- Wong SY, Woo J, Hong A, Leung JC, Kwok T, Leung PC. Risk factors for lower urinary tract symptoms in southern Chinese men. Urology 2006;68:1009–1014.
- Kristal AR, Aronold KB, Schenk JM, Neuhouser ML, Goodman P, Penson DF, Thompson IM. Dietary patterns, supplement use, and the risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial. Am J Epidemiol 2008;167:925–934.
- Coward L, Barnes NC, Setchell KDR, Barnes S. Genistein, daidzein, and their B-glycoside conjugates. Antitumor isoflavones in soybean foods from American and Asian diets. J Agric Food Chem 1993;41:1961–1967.
- Wong SY, Lau WY, Leung PC, Leung JC, Woo J. The association between isoflavone and lower urinary tract symptoms in elderly men. Br J Nutr 2007;98:1237–1242.
- Leung SSF, Ho SC, Woo J, Ho S, La, TH, Janus ED. Hong Kong adult dietary survey 1995, Hong Kong: Department of Paediatrics, Chinese University of Hong Kong; 1995.
- McCance RA. McCance & Widdowson's: the composition of foods. 4th ed. London: HMSO; 1978.
- Yang Y, Wang G, Pan X. Institute of Nutrition & Food Safety, China CDC. China Food Composition. Peking: University Medical Press; 2002.
- Anderson JW. Estimated values for isoflavone content of selected soyfoods. The American Dietetic Association 80th Annual Meeting and Exhibition, 1997 October 27-30; Boston, MA. Available from: http://www.soyfoods.com/nutrition/isoflavoneconcentration.html
- Dwyer JT, Goldin RB, Saul N, Gualtieri L, Barakat S, Adlercreutz H. Tofu and soy drinks contain phytoestrogens. J Am Diet Assoc 1994;94:739–743.
- Barry MJ, Fowler FJ Jr., O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett AT. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992;148:1549–1557.
- Washburn RA. The physical activity scale for the elderly (PASE): development and evaluation. J Clin Epidemiol 1993;46:153–162.
- Liu B, Woo J, Tang N, Tang N, Ng K, Ip R, Yu A. Assessment of total energy expenditure in a Chinese population by a physical activity questionnaire: examination of validity. Int J Food Sci Nutr 2001;52:269–282.
- Chan HC. The psychometric evaluation of the Chinese version of the international prostate symptom score (IPSS). [Thesis]. Hong Kong: Hong Kong University; 2004.
- Lee HB, Chiu HFK, Kwok WY, Leung CM, Kwong PK, Chung DWS. Chinese elderly and the GDS short form: a preliminary study. Clin Gerontol 1993;14:37–39.
- Laumann EO, West SL, Glasser DB, Carson C, Rosen R. Kang JH. Prevalence and correlates of erectile dysfunction by race and ethnicity among men aged 40 or older in the United States: from the Male Attitudes Regarding Sexual Health Survey. J Sex Med 2007;4:57–60.
- Laumann EO, Kang JK, Glasser DB, Rosen R, Carson C. Lower urinary tract symptoms are associated with depressive symptoms in White, Black and Hispanic men in the United States. J Urol 2008;180:233–240.
- Rosen R, Altwein J, Boyle P, Kirby RS, Lukacs B, Meuleman EJH, O'Leary M, Puppo P, Chris R, Giuliano F. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol 2003;44:637–642.
- Fitzgerald MP, Link CL, Litman HJ, Travison TG, McKinlay JB. Beyond the lower urinary tract: the association of urologic and sexual symptoms with common illnesses. Eur Urol 2007;52:407–415.
- Mariappan P, Ballantyne Z, N'Dow JM. Serotononin and noradrenaline reuptake inhibitors (SNRI) for stress urinary incontinence in adults. Cochrane Database Syst Rev 2005;(3): CD004742.
- Roehrborn CG. Lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction, and phosphodiesterase-5 inhibirtors. Rev Urol 2004;6:121–135.