Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common problem with unclear etiology. Some diet and lifestyle factors were thought to correlate with CP/CPPS, but studies comprehensively investigate this correlation are rarely available. The current study was conducted to determine the potential lifestyle-related risk factors of CP/CPPS and its pain severity in Chinese population.
Participants were recruited from seven hospitals in Shanghai from July 2012 to August 2013. Demographics, medical history, diet and lifestyle information, and CP/CPPS symptoms were obtained from each participant using a questionnaire. Univariate and multivariate logistic regression analyses were used to identify potential lifestyle-related risk factors for CP/CPPS and its pain severity.
A total of 784 men with CP/CPPS and 785 controls were enrolled in this study. Multivariate regression model indicated that age, nightshift work, stress, smoking status, alcohol consumption, less water intake, imbalanced diet, frequent sexual activity, delaying ejaculation and holding urine were identified as potential risk factors for CP/CPPS, whereas sedentary lifestyle, caffeinated drinks and less water intake were associated with severe pain in CP/CPPS patients.
Several diet and lifestyle factors associated with CP/CPPS and pain severity were determined in this study. These modifiable conditions are potential targets for treatment of CP/CPPS. However, further studies are necessary to determine their role in the pathogenesis of CP/CPPS.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological problem worldwide. According to National Institutes of Health (NIH) consensus, CP/CPPS is characterized by chronic pelvic pain symptoms without identifiable etiology and classified as type-III prostatitits.1 A widely used questionnaire called the NIH-chronic prostatitis symptom index (NIH-CPSI) was developed for the diagnosis and assessment of CP/CPPS.2 The prevalence of CP/CPPS ranges from 2.2 to 9.7% globally.3 In a cross-sectional study conducted by Liang et al.,4 the prevalence of prostatitis-like symptoms diagnosed through NIH-CPSI was 8.4% in China. Moreover, a substantial impairment in the quality of life and significant economic burden were observed in patients with CP/CPPS.5, 6 However, the etiology of CP/CPPS remains poorly understood.
Previous studies identified a wide range of potential risk factors correlated with CP/CPPS.7, 8 Conflicting results exist in these studies because of the different populations and study designs used. Among these potential risk factors, diet and lifestyle factors such as sexual habit and physical activity are variable and modifiable in different regions and populations. However, rarely had any study that comprehensively reported the lifestyle factors associated with CP/CPPS in Chinese population. Hence, we conducted a case–control study to investigate the association of diet and lifestyle factors with CP/CPPS and its pain severity among patients in Shanghai, China.
Materials and methods
Participants were consecutively recruited from seven hospitals (Ren Ji Hospital, Zhongshan Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Longhua Hospital, Shanghai Eighth People's Hospital, East Hospital and Shanghai First People's Hospital) in Shanghai from July 2012 to August 2013. Men aged 18–65-year old were enrolled in this study, which was approved by the ethics committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Informed consent was signed by each participant.
The selection criteria for CP/CPPS group were as follows: (1) discomfort or pain in the pelvic region or perineum; (2) symptoms lasting for at least 3 months; and (3) NIH-CPSI pain score of ⩾4.2 Most participants in the CP/CPPS group were recruited from outpatients with CP/CPPS at the urology/andrology departments of the seven hospitals.
Controls were volunteers who did not present any prostatitis-related symptoms. All the controls were recruited from the physical examination centers of the seven hospitals. Some CP/CPPS patients were identified from these volunteers in accordance with the selection criteria.
Clinical and laboratory evaluation
The patients underwent digital rectal examination, expressed prostatic secretion microscopy and microbial culture, urinalysis, urine microbial culture and transrectal ultrasonography. The controls underwent urinalysis, urine microbial culture and transabdominal ultrasonography. Those participants older than 50 years underwent a serum PSA test to rule out prostate cancer.
Those participants suspected of having BPH with a post-void residual urine volume of >50 ml were excluded. Those participants with evidence suggesting elevated PSA, prostate nodule, urinary tract infection, proteinuria, hematuria and other NIH types of prostatitis were also excluded.
The self-administered questionnaire contained questions concerning basic information, lifestyle and NIH-CPSI. Demographic characteristics, related medical history and symptoms were collected as basic information. Body mass index (BMI) was calculated and categorized according to World Health Organization criteria for Asia Pacific region: underweight (BMI<18.5 kg/m2), normal (18.5⩽BMI<23.0 kg/m2), overweight (23.0⩽BMI⩽27.5 kg/m2) and obese (BMI>27.5 kg/m2).9 Means of transportation, sedentary lifestyle, physical activity, nightshift work, sleep disorder, stress, smoking status, alcohol consumption, caffeinated drinks, water intake, spicy food in diet, dietary factors, frequency of sexual activity, delaying ejaculation and holding urine were assessed in the lifestyle-related questions. Patients were required to recall their lifestyle when the symptoms first appeared. Definition of lifestyles and the English version of questionnaire assessing diet and lifestyle factors are available in Supplementary Information. NIH-CPSI scores comprised three domains: pain score (0–21), urinary symptom score (0–10) and quality-of-life impact score (0–12).2 According to Nickel et al.,10 patient with pain score of ⩾4 and ⩾8 were defined as having prostatitis-like symptoms and moderate to severe symptoms, respectively.
A total of 2000 self-administered questionnaires were distributed to the seven hospitals, of which 560 were assigned to Ren Ji Hospital. Each of the other six hospitals received 240 questionnaires. Half of these questionnaires were assigned to volunteers in physical examination centers. The objective of this questionnaire was explained to all the participants. Questioning for incomprehensive items was also encouraged.
The exclusion criteria for all the participants were as follows: (1) medical history of BPH, epididymitis, urethral stricture, severe varicocele, neurogenic bladder, major depression and urethral surgery; (2) previous urinary tract infection within 3 months; (3) current use of antimicrobials; and (4) consumption of medications, such as α-blockers or 5α-reductase inhibitors, which affected the lower urinary tract function within the previous month. Those volunteers with urinary symptom score of >4 were excluded from the control group because this result indicates a certain degree of lower urinary tract symptoms.
Data entry was completed by two independent programmers (CH and XC) using EpiData version 3.1 (The EpiData Association, Odense, Denmark). Discrepancy was corrected by reviewing the original questionnaire. A questionnaire was considered invalid if the NIH-CPSI was incomplete, or any mismarked question was found. Finally, 784 and 785 valid questionnaires were obtained from the CP/CPPS and control groups, respectively, which both met the selection and exclusion criteria. Steps for selection are available in Supplementary information.
Shapiro–Wilk test was used to check the normality, whereas Wilcoxon rank-sum test and χ2-test were used to compare the demographic characteristics. Two-tailed test was also performed, and a P-value of <0.05 was considered statistically significant. Univariate logistic regression model was used to estimate the unadjusted odds ratio (OR) and 95% confidence interval (CI) of all possible variables. The ORs of age and BMI were calculated as measurement and categorical data. Multivariate logistic regression model was used to estimate the adjusted OR and 95% CI. To adjust for multivariate regression, variables with statistical significance of P<0.2 were selected. Categorical data were entered in the multivariate model as dummy variables, whereas age and BMI were entered as measurement variables, and sleep disorder and water intake were entered as ranked variables. All statistical analyses were performed using SAS version 8.02 (SAS Institute, Cary, NC, USA).
Risk factors for CP/CPPS
The demographic information and NIH-CPSI scores of the CP/CPPS and control groups are listed in Table 1. The difference in educational level between the CP/CPPS and control groups was statistically significant (P<0.001). A higher proportion of participants in the control group have received college education. This difference can be attributed to the selection of the control group in the physical examination center, given that people with higher education are more concerned about their health state.
The obtained lifestyle factors and unadjusted ORs are compared in Table 2. The ORs of age calculated for measurement or categorical variables indicated that increased age was a potential risk factor for CP/CPPS. Increased BMI was also a potential risk factor for CP/CPPS (unadjusted OR=1.04, P=0.030). However, upon analysis of the categorical variables, this trend was not statistically significant in underweight and obese patients because of the relatively small sample size in these two levels. Moreover, public transport showed a protective effect for CP/CPPS compared with walking (unadjusted OR=0.59, P<0.001). Bicycle/motorcycle was a possible risk factor for CP/CPPS, but this factor demonstrated a marginal P-value (unadjusted OR=1.32, P=0.057). Nightshift work, sleep disorder, stress, smoking, alcohol consumption, spicy food, delaying ejaculation and holding urine all demonstrated negative effects on CP/CPPS, whereas increased water intake was a protective factor for CP/CPPS. Both vegetable- and meat-preferred diets were associated with increased risk of CP/CPPS. In addition, sexual activity of more than twice a week was a possible risk factor for CP/CPPS compared with only once to twice per week, whereas sexual activity of less frequent than once a week was statistically insignificant.
Table 3 summarizes the adjusted ORs of lifestyle factors for CP/CPPS. A total of 674 and 709 participants in the CP/CPPS and control groups were included in the multivariate analysis. Age, BMI, means of transportation, physical activity, nightshift work, sleep disorder, stress, smoking status, alcohol consumption, water intake, spicy food in diet, dietary factors, sexual activity, delaying ejaculation and holding urine were adjusted in the multivariate model. Age, nightshift work, stress, smoking status, alcohol consumption, vegetable- or meat-preferred diets, sexual activity of more than twice a week, delaying ejaculation and holding urine were identified as potential risk factors for CP/CPPS. By contrast, increased water intake was a potential protective factor for CP/CPPS.
Risk factors for pain severity
Demographic information and NIH-CPSI scores of mild and moderate to severe patients with CP/CPPS are listed in Table 4. Statistical significance existed in the NIH-CPSI scores, but not in the demographic information.
The lifestyle factors and unadjusted ORs for pain severity are compared in Table 5. Increased BMI was a potential risk factor for pain severity (unadjusted OR=1.09, P=0.013). However, owing to the small sample size, the trend was not significant in underweight and obese levels. Smoking, alcohol consumption, caffeinated drinks and holding urine showed adverse effects on the pain symptoms of CP/CPPS. A marginal P-value was observed (P=0.052) for sedentary lifestyle, whereas sleep disorder and water intake demonstrated a protective effect on pain severity.
Multivariate-adjusted ORs of the lifestyle factors for CP/CPPS pain severity are demonstrated in Table 6. A total of 712 participants from the CP/CPPS group were included in the multivariate analysis. Age, BMI, means of transportation, sedentary lifestyle, sleep disorder, smoking status, alcohol consumption, caffeinated drinks, water intake and holding urine were adjusted in multivariate logistic regression. Sedentary lifestyle and caffeinated drinks were identified as potential risk factors for pain aggravation, whereas increased water intake was associated with mild pain symptoms.
The etiology of CP/CPPS remains unknown. Previous studies have revealed that some lifestyles were associated with increased risk of CP/CPPS.7, 8 However, inconsistent results exist because lifestyle varies in different countries and populations.7 Therefore, the present case–control study was conducted to systematically investigate the association between lifestyle factors and CP/CPPS along with its pain severity in Chinese population.
Age is a potential risk factor of many diseases. Previous studies indicated that CP/CPPS is more prevalent in older people.11, 12, 13 The result from a study including participants older than 65 years did not support this association but indicated an inverted U-shaped trend.14 In the current study with ages ranging from 18- to 65-year old, age was a potential risk factor for CP/CPPS (adjusted OR=1.04), which is in accordance with preceding studies that only included men younger than 65 years. Although the mechanism is unclear, the refractory and recurrent characteristics of CP/CPPS may contribute to the association between age and CP/CPPS, and selection bias may also contribute to the difference in age between groups.
Few studies reported the correlation between nightshift work and CP/CPPS. The present study indicated that nightshift work was a potential risk factor for CP/CPPS (adjusted OR=1.59). Previous studies have found that hormone abnormality, particularly for adrenocortical hormones, was associated with CP/CPPS.15, 16 Furthermore, estrogen or analog administration can induce prostatitis in rodents,17, 18 and nightshift work leads to an untimely production of sex hormones and cortisol.19, 20 These results support the hypothesis that nightshift work changes the circadian rhythm of hormone secretion and induces prostatitis. Moreover, stress has been previously reported to be associated with CP/CPPS.21 The effects of stress on cortisol secretion may explain this association.16, 22 However, whether stress causes or results from CP/CPPS was difficult to determine in the present study.
Smoking cigarettes tended to enhance pain sensitivity, and a dose–response relationship was found between frequent pain and tobacco consumption.23 However, results were inconsistent for CP/CPPS. Some studies found a statistical difference in smoking status between patients with CP/CPPS and controls,4, 24 whereas others found no correlation,21, 25, 26 and most of the studies failed to report an adjusted result. Zhang et al.27 reported no association between CP/CPPS and smoke in a large cohort study. However, this cohort was based on health professionals who may have a healthier lifestyle. In this case, although smoking is a potential risk factor with a plausible explanation, further evidence is necessary to determine its role on CP/CPPS.
Alcohol consumption was also associated with CP/CPPS in this study (adjusted OR=1.34). Acetaldehyde is an ethanol metabolite that can induce autacoid release and vasodilation.28 This reaction may lead to prostate congestion and contribute to inflammation. Some previous studies have drawn the same conclusion with our study;4, 21, 29 however, inconformity still exists.24, 25, 26
Rarely had any study reported drinking water as a protective factor for CP/CPPS. In the current research, this protective effect was distinct (adjusted OR=0.42), but the underlying mechanism was unknown. Holding urine was also found to be associated with CP/CPPS (adjusted OR=2.63). The compression of distended bladder on prostate may contribute to the pathogenesis of CP/CPPS, and increased frequency of micturition that releases pressure to the prostate may be protective.
In addition, imbalanced diet was associated with CP/CPPS. Meat-preferred diet lacks cellulose supplementation, thereby causing constipation. Chronic constipation would further promote pelvic muscle spasm, resulting in pelvic pain. Meat-preferred diet also contains excessive calories, which may be harmful to the prostate, as previously reported by Bartoletti et al.24 Vegetable-preferred diet can increase stool bulk and relieve symptoms of constipation.30 The adverse effects were flatulence, abdominal distension and occasional stool impaction, which was harmful to the prostate. Hence, this type of diet was not recommended to patients with refractory pelvic floor dyssynergia, which is common in men with CP/CPPS.31 Findings of Díaz-Mohedo et al.32 were similar to the present results.
Frequency of sexual activity was reported to correlate with CP/CPPS.8 Regular ejaculation can clean the stored secretion of prostatic gland and seminal vesicles, thus preventing prostatic congestion and swelling, and excessive number of sexual intercourse is a source of pelvic floor muscle spasm and tenderness. Therefore, sexual abstinence and excessive sex were both risk factors for CP/CPPS. However, in the present study, only excessive sex was associated with CP/CPPS (adjusted OR=1.43). The habit of delaying ejaculation can also lead to musculature tenderness and was identified as a potential risk factor for CP/CPPS in our study (adjusted OR=2.51), similar to the result obtained by Bartoletti et al.24
The demographic characteristics and lifestyles between mild and moderate to severe patients with CP/CPPS were more homogenous than those of controls. Most potential risk factors for CP/CPPS showed insignificance with pain severity. Increased water intake remained a protective factor for pain severity (adjusted OR=0.40). In this study, sedentary lifestyle and caffeinated drinks showed no association with CP/CPPS but were identified as potential risk factors for pain aggravation (adjusted OR=1.88 and 1.74, respectively). Anecdotal reports considered sedentary lifestyle and bicycling as risk factors for CP/CPPS. However, Collins et al.21 provided contrary evidence that men who rode bicycles were at no greater odds of having CP/CPPS. In our study, sedentary lifestyle was not associated with CP/CPPS but may probably intensify pain severity in CP/CPPS patients, with a plausible explanation of increasing pelvic congestion. Moon et al.33 and Herati et al.29 reported that caffeine intake made CP/CPPS symptoms worse, which was consistent with our findings.
Spicy food was anecdotally thought to be a risk factor for CP/CPPS, but neither for CP/CPPS nor pain severity in the current study. Although Herati et al.29 demonstrated that spicy food can aggravate the symptoms of pain, the results were mainly based on subjective reports of CP/CPPS patients only but not on regression analysis.
Physical activity was also reported as a protective factor for CP/CPPS,25 as confirmed by cohort studies.34, 35 Our study failed to demonstrate this trend, probably because participants with low-intensity exercise were included in the physical activity category, whereas in preceding studies, the protective effect was mostly found in men doing strenuous and prolonged exercises.
Recall bias exists in any case–control studies using self-report of patients; therefore, the results may overestimate the association between lifestyle factors and CP/CPPS. Furthermore, demonstrating the cause–effect relationship was difficult given the nature of case–control design. Although participants were recruited in different types of hospitals to include diverse sources of patients, selection bias was not completely avoided, compared with community-based study. Our exclusion criteria preluded CP/CPPS patients with certain comorbidities or medical conditions, thus the results cannot represent these populations. Considering that this study was based on a Chinese population and various lifestyles in different cultures, the results should be applied to other ethnic groups with caution. Some lifestyle factors were not stratified in detail. For example, smoking status was only considered as current, hence the loss of some information. Despite the above limitations, this study is one of the few to comprehensively investigate the relationships between lifestyle-related factors and CP/CPPS. Lifestyle modification may therapeutically affect CP/CPPS. In fact, this hypothesis was verified by randomized clinical trial by Gallo in Italy.8 Therefore, lifestyle modification may be a promising, effective, convenient and inexpensive therapy for CP/CPPS.
In summary, lifestyle factors were associated with CP/CPPS in Chinese population. Age, nightshift work, stress, smoking, alcohol consumption, less water intake, imbalanced diet, frequent sexual activity, delaying ejaculation and holding urine were identified as potential risk factors for CP/CPPS. Sedentary lifestyle, caffeinated drinks and less water intake were associated with severe pain in patients with CP/CPPS. Therefore, lifestyle modification, especially avoidance of sedentary life and caffeinated drinks, and more water intake may relieve symptoms of CP/CPPS; however, further evidence is needed.
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The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website
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Chen, X., Hu, C., Peng, Y. et al. Association of diet and lifestyle with chronic prostatitis/chronic pelvic pain syndrome and pain severity: a case–control study. Prostate Cancer Prostatic Dis 19, 92–99 (2016). https://doi.org/10.1038/pcan.2015.57