Natural history of lower urinary tract symptoms in Japanese men from a 15-year longitudinal community-based study

Authors


Naoya Masumori, Department of Urology, Sapporo Medical University School of Medicine, S1W16, Sapporo, Hokkaido 060-8543, Japan. e-mail: masumori@sapmed.ac.jp

Abstract

Study Type – Symptom prevalence (cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

There have been few longitudinal community-based studies on LUTS suggestive of BPH. It is important to determine the natural history of LUTS suggestive of BPH among men in various countries because it is known that there are differences according to race. Although we previously reported a cross-sectional community-based survey on LUTS suggestive of BPH in Japanese men, no longitudinal data were available.

The present study provides 15-year longitudinal data on LUTS suggestive of BPH and related variables in Japanese men.

OBJECTIVE

  • • To report the natural history of benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in Japanese men.

PATIENTS AND METHODS

  • • From 1992 to 1993, we conducted a cross-sectional community-based study on LUTS suggestive of BPH in Japanese men aged 40–79 years.
  • • After 15 fifteen years, a follow-up study was conducted to determine their longitudinal changes of LUTS.
  • • Of the 319 participants taking part in the initial study, 135 participated again in the follow-up study.
  • • We investigated International Prostate Symptom Score (IPSS), quality of life index and bother score using a questionnaire, and measured prostate volume (PV), prostate-specific antigen (PSA) level and peak urinary flow rate (Qmax) using a method that we have employed previously.

RESULTS

  • • The change in the total IPSS during 15 years was significant (P= 0.001) and its mean (sd) annual change was 0.11 (0.40).
  • • Although there was little change in the bother score, a significant correlation was observed between changes in the IPSS and bother score (r= 0.528, P < 0.001).
  • • For the individual IPSS and bother scores, only changes in urgency, weak stream and nocturia were significant.
  • • The changes in PV, PSA level and Qmax were significant.
  • • The change in the total IPSS did not correlate with the changes in these variables.

CONCLUSION

  • • In a 15-year-longitudinal community-based study for Japanese men, we have shown that the IPSS and quality of life index deteriorated, PV and PSA level increased, and Qmax decreased.
Abbreviations
PV

prostate volume

Qmax

peak urinary flow rate

QoL

quality of life.

INTRODUCTION

Cross-sectional population- and community-based studies on LUTS suggestive of BPH from various countries have shown that LUTS deteriorate with age [1–6]. The Olmsted County Study from the USA [2,7,8] and the Krimpen study from the Netherlands [1,9] represent landmark studies, although few longitudinal population- or community-based studies have been reported. There are differences in the prevalence of LUTS among men by country [10], possibly as a result of cultural or linguistic differences. Because this finding suggests that the results in one country may not be applicable to other countries, it is necessary to investigate the natural history of LUTS in each one.

We previously conducted a cross-sectional community-based study on LUTS suggestive of BPH in Japanese men [4,10]. That study used the same protocol as the Olmsted County Study, so we could compare the prevalence of LUTS in Japanese men with that in American men [4], and found that it was higher in Japanese than in Americans, whereas the bother score in Japanese was lower.

Some 3 years after the initial study, we performed a longitudinal survey on LUTS [11]. However, no significant changes in the symptoms were observed, probably because of the short follow-up period. In the present study, we conducted a community-based survey again, ≈15 years after the initial study, aiming to clarify longitudinal changes in LUTS suggestive of BPH and their relationships with other urological variables.

PATIENTS AND METHODS

From October 1992 to May 1993, we conducted a cross-sectional community-based study aiming to determine the prevalence of LUTS suggestive of BPH in men aged 40–79 years in Shimamaki-mura, Hokkaido, Japan [4,10]. From February 2007 to February 2008, we conducted a longitudinal survey using the same methods as those employed in the initial survey. The present study was approved by the Sapporo Medical University Ethics Committee in February 2007 (#18–9).

The present study was conducted in cooperation with the Welfare Division of Shimamaki-mura. They provided information about the life and death of participants in the initial survey from the resident registry file. Survivors were invited to participate in the longitudinal survey by mail and they were informed about the purpose of the study. Survivors who provided their written informed consent to participate were included in the study.

The IPSS, quality of life (QoL) index, bother score, prostate volume (PV), PSA level, peak flow rate (Qmax) and medical history were all investigated. An increase and decrease in the IPSS ≥4 was considered to indicate symptom progression and improvement, respectively, in accordance with the criteria of the Krimpen and MTOPS studies [9,12,13]. PV was measured by a single examiner (F.F.) and estimated using a previously reported formula [10,14,15]. Serum PSA levels were measured with an equimolar TOSOH II PSA kit (Tosoh, Tokyo, Japan). Qmax was measured using a mediwatch Urodyn 1000 System (Medtronic Inc., Minneapolis, MN, USA). All subjects voided when they were standing. If the voided volume was <150 mL, they were requested to retry. If the voided volume did not reach 150 mL despite repeated examination, we adopted the flow rate from the maximal voided volume as Qmax. Patients were also asked about their medical history and current medication. Insufficient information was supplemented by medical charts from the clinics and the hospitals that they visited.

PARTICIPANTS

In the initial study, 319 of the 682 (47%) men aged 40–79 years who resided in Shimamaki-mura participated (Fig. 1) [4]. Of them, 185 (58%) survived and resided in Shimamaki-mura in January 2007. Of the remaining 134, 96 had died and 38 had moved away during 15 years. Of the 185 survivors, 135 (73%) participated in the longitudinal survey.

Figure 1.

Participants in the present study. PV, prostate volume; Qmax, peak urinary flow rate.

In total, 51 men experienced 72 events that affected the inclusion criteria in the present study: TURP (n= 15), medication by an α-blocker (n= 15), back surgery (n= 10), apoplexy (n= 7), prostate cancer (n= 10), transurethral resection of bladder cancer (n= 3), antiandrogen medication (n= 2), haemodialysis (n= 1), neurogenic bladder (n= 1) and missing data (n= 8). In total, 19 men had two events and one had three events. Subjects who did not meet the inclusion criteria were excluded from analysis in the relevant categories.

STATISTICAL ANALYSIS

Differences in the IPSS, QoL index, bother score, PV, PSA level and Qmax between baseline and follow-up were analyzed by the Wilcoxon signed-ranks test. Spearman's rank correlation method was used for evaluating any correlations between baseline and dynamic variables, as well as among dynamic variables. P < 0.05 was considered statistically significant. Scatter plots were used to show changes in the IPSS and bother score during 15 years against the baseline. Regression lines of these changes were estimated by the least-squares method. Statistical analyses were performed using SPSS, version 15.0 (SPSS Inc., Chicago, IL, USA).

RESULTS

The median (range) age of the participants was 73 (53–94) years. The overall re-participation rate was ≈42%. The median (range) follow-up period was 14.4 (13.8–15.3) years.

CHANGES IN IPSS, QOL INDEX AND BOTHER SCORE

Changes in the IPSS, QoL index and bother score (Table 1) could be evaluated in 91 men. Of the 44 men who were excluded from evaluation, 22 had treatment for LUTS during ≈15 years: one (2.1%) in his forties, five (7.7%) in their fifties, 12 (11.2%) in their sixties and four (5.7%) in their seventies at baseline. The changes in the IPSS increased with age, except for men in their seventies. The mean annual change in the IPSS was 0.11 points per year. The largest mean annual change was seen in men in their sixties. The QoL index also showed a significant increase with the IPSS, which significantly increased. For the bother score, there was no significant change, except for men in their fifties. Significant IPSS changes were seen in urgency, weak stream and nocturia (Table 2). Similarly, significant changes in bother scores were seen for urgency, weak stream and nocturia.

Table 1.  IPSS, quality of life (QoL) index and bother score by age decade at baseline and follow-up, as well as longitudinal changes
Age at baseline (years) N Eligible participants at baseline, nRe-participation rate (%)Baseline, mean (sd)Follow-up, mean (sd)Mean (sd) change P Annual change, mean (sd)
  • *

    Statistically significant difference (P < 0.05).

IPSS (0–35)        
 40–49294761.77.3 (4.7)8.1 (4.6)0.8 (5.6)0.6730.05 (0.38)
 50–59276541.55.6 (5.4)7.0 (4.3)1.4 (5.8)0.017*0.10 (0.40)
 60–692810726.27.0 (4.6)9.7 (4.8)2.7 (5.0)0.008*0.19 (0.24)
 70–7977010.010.0 (6.2)11.4 (8.1)1.4 (8.3)0.3980.10 (0.56)
 Total9128931.56.9 (5.0)8.5 (5.0)1.6 (5.7)0.001*0.11 (0.40)
QoL index (0–6)        
 40–49294761.72.0 (1.7)2.1 (1.4)0.1 (1.6)0.8370.00 (0.11)
 50–59276541.51.2 (1.0)2.3 (1.6)1.0 (1.5)0.002*0.07 (0.11)
 60–692810726.21.6 (1.1)2.2 (1.3)0.6 (1.4)0.036*0.04 (0.10)
 70–7977010.02.7 (1.4)3.6 (1.0)0.9 (0.9)0.0630.06 (0.06)
 Total9128931.51.7 (1.4)2.3 (1.4)0.6 (1.5)0.001*0.04 (0.11)
Bother score (0–28)        
 40–49294761.73.7 (4.7)4.5 (4.3)0.8 (4.1)0.3710.05 (0.28)
 50–59276541.52.4 (3.3)4.4 (5.5)2.0 (4.2)0.012*0.14 (0.29)
 60–692810726.24.4 (5.9)4.8 (5.3)0.4 (7.2)0.9760.03 (0.50)
 70–7977010.05.9 (6.0)7.0 (6.7)1.1 (5.9)0.4390.08 (0.40)
 Total9128931.53.7 (4.9)4.8 (5.1)1.0 (5.4)0.0740.07 (0.37)
Table 2.  Individual IPSS and bother scores at baseline and follow-up, as well as changes
VariableBaselineFollow-upMean change P
  • *

    Statistically significant difference (P < 0.05). Data are the mean (sd).

IPSS 1: Not empty0.9 (1.1)0.9 (1.0)0.0 (1.2)0.793
IPSS 2: Day frequency1.4 (1.3)1.5 (1.2)0.1 (1.4)0.611
IPSS 3: Stop/start0.7 (1.1)0.8 (1.0)0.1 (1.3)0.517
IPSS 4: Urgency0.8 (1.1)1.1 (1.1)0.3 (1.3)0.043*
IPSS 5: Weak stream1.2 (1.2)1.6 (1.5)0.5 (1.6)0.003*
IPSS 6: Straining0.8 (1.0)0.9 (1.0)0.1 (1.4)0.494
IPSS 7: Nocturia1.1 (0.9)1.6 (1.2)0.5 (1.1)<0.001*
Bother 1: Not empty0.6 (0.9)0.5 (1.0)0.0 (1.0)0.755
Bother 2: Day frequency0.5 (0.9)0.7 (1.1)0.2 (1.1)0.070
Bother 3: Stop/start0.5 (0.8)0.4 (0.8)0.0 (1.0)0.676
Bother 4: Urgency0.5 (1.0)0.9 (1.3)0.3 (1.3)0.015*
Bother 5: Weak stream0.8 (1.1)1.1 (1.3)0.3 (1.4)0.044*
Bother 6: Straining0.4 (0.8)0.4 (0.7)−0.1 (0.8)0.365
Bother 7: Nocturia0.5 (0.9)0.9 (1.2)0.3 (1.2)0.010*

The IPSS deteriorated in ≈40% of men (Table 3), although 13% of them showed an improvement in IPSS. Half of the men had a stable IPSS. The rate of symptom progression increased with age. During the 15-year follow-up, 50% of men with an IPSS in the range 0–7 at baseline had symptom progression. In men with an IPSS in the range 8–19 at baseline, 50% had stable symptoms. The remaining 50% comprised 25% with improvement and 25% with symptom progression. Men with higher IPSS and lower IPSS tended to have decreased and increased IPSS, respectively (Fig. 2). Similar results were obtained for the bother score.

Table 3.  Changes in symptoms by age decade and IPSS at baseline
Variable N Changes in symptoms
ImprovementStableProgression
  1. Improvement: decrease in IPSS ≥ 4; Progression: increase in IPSS ≥ 4; Stable: change in IPSS < 4. Data are the mean (sd).

Total, n (%)9112 (13.2)44 (48.4)35 (38.5)
Age at baseline (years)    
 40–49296 (20.7)16 (55.2)7 (24.1)
 50–59272 (7.4)15 (55.6)10 (37.0)
 60–69283 (10.7)11 (39.3)14 (50.0)
 70–7971 (14.3)2 (28.6)4 (57.1)
IPSS at baseline    
 0–7592 (3.4)29 (49.2)28 (47.5)
 8–19308 (26.7)15 (50.0)7 (23.3)
 20–3522 (100.0)0 (0.0)0 (0.0)
Figure 2.

The scatter plots show changes in the IPSS and bother score against the IPSS and bother score at baseline. The broken lines indicate regression lines (points per year): IPSS (slope =−0.64, intercept = 6.01, r2= 0.325, P < 0.001) and bother score (slope =−0.55, intercept = 3.08, r2= 0.251, P < 0.001).

CHANGES IN PV AND PSA LEVEL

PV was evaluable in 104 men and PSA level was evaluable in 111 men (Table 4). PV significantly increased with age overall, as well as in all age decades during the 15 years, as did PSA.

Table 4.  Prostate volume (PV), PSA level and peak urinary flow rate (Qmax) at baseline and follow-up, as well as changes
Variable N Eligible participants at baselineRe-participation rate (%)Baseline, mean (sd)Follow-up, mean (sd)Mean (sd) change P Mean annual change, mean (sd)
  • *

    Statistically significant difference (P < 0.05).

PV (mL)        
 40–49314667.417.5 (4.0)24.3 (7.5)6.8 (5.6)<0.001*0.47 (0.38)
 50–59326549.217.9 (4.1)25.5 (9.1)7.6 (8.3)<0.001*0.52 (0.57)
 60–693110529.520.0 (6.8)30.5 (16.8)10.5 (12.2)<0.001*0.71 (0.83)
 70–79107114.118.4 (5.9)33.0 (18.1)14.6 (13.1)0.005*1.00 (0.90)
 Total10428736.218.5 (5.2)27.3 (12.7)8.9 (9.7)<0.001*0.61 (0.66)
PSA level (ng/mL)        
 40–49314867.40.8 (0.7)1.6 (1.7)0.8 (1.4)<0.001*0.06 (0.10)
 50–59346850.00.7 (0.4)1.5 (1.2)0.8 (1.0)<0.001*0.06 (0.07)
 60–693511331.01.0 (0.8)2.6 (2.6)1.6 (2.3)<0.001*0.11 (0.17)
 70–79117315.11.1 (0.5)3.6 (4.1)2.5 (3.7)0.009*0.17 (0.25)
 Total11130236.80.9 (0.6)2.1 (2.3)1.2 (2.0)<0.001*0.09 (0.14)
Qmax (mL/s)        
 40–49294761.722.5 (8.2)21.0 (7.1)−1.4 (9.6)0.352−0.10 (0.67)
 50–59266341.323.3 (6.8)18.8 (7.8)−4.4 (9.0)0.025*−0.31 (0.62)
 60–692810626.417.8 (9.3)15.7 (6.8)−2.1 (9.3)0.239−0.14 (0.65)
 70–7976910.114.1 (6.0)13.6 (5.8)−0.5 (5.8)0.611−0.03 (0.40)
 Total9028531.620.6 (8.5)18.1 (7.5)−2.4 (9.1)0.014*−0.17 (0.63)

CHANGE IN Qmax

Qmax was evaluable in 90 men (Table 4). The overall change in Qmax significantly decreased with time. The changes in Qmax by age decade were not significant, except for men in their fifties.

CORRELATIONS AMONG VARIABLES

We evaluated correlation coefficients (r) between variables at baseline and changes indicating dynamic variables (Table 5). There was a significant correlation between baseline age decade and the change in PSA level. Inverse correlations were observed among the baseline IPSS, QoL index and bother score, as well as the dynamic IPSS, QoL index and bother score, except for the baseline IPSS vs dynamic bother score and baseline QoL index vs dynamic bother score. Baseline PV correlated with PV growth and change in PSA level, as did baseline PSA level. Baseline Qmax correlated inversely with the change in Qmax.

Table 5.  Correlations between baseline variables and their changes
Variables at baselineDynamic variables over time
IPSSQoL indexBother scorePV (mL)PSA level (ng/mL)Qmax (mL/s)
  • *

    Statistically significant difference (P < 0.05). PV, prostate volume; Qmax, peak urinary flow rate; QoL, quality of life.

Age      
 r0.1770.135−0.0400.1700.208−0.033
 P0.0930.2010.7040.0850.028*0.758
 n91919110411190
IPSS      
 r −0.425−0.313−0.1270.0360.0050.156
 P0.001*0.003*0.2290.7140.9580.142
 n91919110411190
QoL index      
 r −0.217−0.490−0.183−0.008−0.0160.223
 P0.039*0.001*0.0820.9350.8680.035*
 n91919110411190
Bother score      
 r −0.351−0.299−0.4200.1530.0070.132
 P0.001*0.004*0.001*0.1320.9450.215
 n9191919810590
PV      
 r 0.0540.0340.0930.3230.3330.138
 P 0.6240.7550.3950.001*0.001*0.204
 n86868610410486
PSA level      
 r 0.127−0.100−0.0400.4280.391−0.003
 P0.2340.3470.7100.001*0.001*0.981
 n90909010411190
Qmax      
 r 0.0190.0820.100−0.0770.029−0.599
 P0.8600.4430.3500.4380.7660.001*
 n90909010411190

We also evaluated correlation coefficients among dynamic variables (Table 6). Correlations among changes in the IPSS, QoL index and bother score were all significant. There was a strong correlation between the changes in PV and PSA level. However, there were no correlations between subjective dynamic variables (IPSS, QoL and bother score) and objective dynamic variables (PSA level and PV).

Table 6.  Correlations between changes in variables
Dynamic variablesDynamic variables
QoL indexBother scorePVPSA levelQmax
  • *

    Statistically significant difference (P < 0.05). PV, prostate volume; Qmax, peak urinary flow rate; QoL, quality of life.

IPSS     
 r 0.3130.5280.0530.041−0.077
 P0.003*0.001*0.6310.7020.471
 n9191848890
QoL index     
 r  0.2950.0610.068−0.055
 P 0.005*0.5840.5260.606
 n 91848890
Bother score     
 r   −0.144−0.153−0.059
 P  0.1920.1540.579
 n  848890
PV     
 r    0.573−0.025
 P   0.001*0.824
 n   10484
PSA level     
 r     −0.133
 P    0.217
 n    88

DISCUSSION

The present study reports the natural history of LUTS suggestive of BPH and related variables in Japanese men in a 15-year longitudinal survey. The present study comprised the first longitudinal community-based study to investigate LUTS using IPSS that also measured PV by TRUS.

IPSS, QOL INDEX AND BOTHER SCORE

Masumori et al. [11] reported longitudinal changes in the IPSS, QoL index and bother score in a 3-year follow-up study. Although their study did not show a significant progression of symptoms, definitive changes were found in the IPSS and QoL index in Japanese men in the present study. In men aged in their fifties, changes in the IPSS, QoL index and bother score were significant. Although the largest mean annual change in the IPSS was seen in men in their sixties, the bother score did not significantly change. Because the treatment rate for LUTS in men in their sixties was high, men with much bother were probably excluded from the analysis.

The mean annual change in the IPSS in 91 men was 0.11 in the present study. In Olmsted County, it was 0.29 at 66-month follow-up [8]. However, cross-sectional data showed that Japanese men had higher symptom prevalence than American men [4]. Regression to the mean probably affected the result [16]. Because the rate for Japanese men with moderate symptoms was higher than for American men at baseline [4], this background may also have affected the lower mean annual increase in Japanese men.

Masumori et al. [11] suggested that one-third of participants reported improved, stable and worsened IPSS at 3-year follow-up [11]. The present study showed that the proportion of changes in symptoms was different from the previous study. However, 13% of participants showed an improvement in their IPSS even at 15-year follow-up. That the symptom progression was seen more often in men with an IPSS in the range 0–7 than in those with an IPSS ≥8 also indicated regression to the mean. Men with many symptoms and bother were probably excluded from the analysis because they were already treated with urological management.

There was little change in the bother score in Japanese men, as in American men [8]. This may reflect the finding that Japanese men reported symptoms more than bother. However, there may be bias because men who underwent treatment for their bothersome symptoms were excluded from the present study.

INDIVIDUAL IPSS

A previous cross-sectional study [4] reported that urgency, weak stream and nocturia were strongly related to age in Japanese men. The present 15-year longitudinal survey confirmed that only the changes in these symptoms were consistently significant. Moreover, bother scores corresponding to these symptoms showed significant changes despite the fact that there was no change in the overall bother score. In the Olmsted County study, all symptoms were related to ageing, with the strongest associations for weak stream and nocturia. However, the changes in individual bother scores in American men did not show significant associations with ageing. Thus, LUTS showing age-related increases and their impact on QoL may be different between countries.

CORRELATIONS WITH VARIOUS VARIABLES

Subjective variables at baseline did not show any correlations with other objective dynamic variables. Inverse correlations were observed among subjective symptoms. Regression to the mean may have been involved in these results because Masumori et al. [11] noted a similar tendency in their 3-year follow-up study.

The present study showed strong correlations among baseline PV, baseline PSA level, PV growth and change in PSA level. Oesterling et al. [17] reported a correlation between PV and PSA level in cross-sectional data. Because this correlation was also verified by the present longitudinal community-based study, the use of PSA level as a surrogate for PV was validated in Japanese men.

Jacobsen et al. [18] and Girman et al. [19,20] noted that population- and community-based studies, unlike clinic-based studies, can show modest correlations among LUTS, Qmax and PV because the former exclude bias as much as possible. However, the present study did not find such correlations. One reason for this was the small number of participants. No correlation was observed among changes in the IPSS, QoL index or bother score and changes in PV or PSA level. St Sauver et al. [21] reported correlations among the Qmax, IPSS, PV and PSA level in the longitudinal study of Olmsted County. Although modest correlations were observed among these variables, significant correlations (Spearman's rank correlation) were seen only between the IPSS and Qmax (r=−0.11, P= 0.01) and PV and PSA level (r= 0.14, P= 0.001), and the correlation coefficients were lower than in the cross-sectional data reported by Girman et al. [19]. In the present study cohort, a similar correlation was seen between PV and PSA level. St Sauver et al. [21] concluded that lower correlations among these variables were affected by the high variability of these measurements.

LIMITATIONS

The number of subjects employed in the present study was smaller than in other large-volume longitudinal surveys. It appeared that the 15-year interval affected the results because the number of men who met exclusion criteria and died increased with time. The re-participation rate was only 42% for the 319 men who participated in the baseline study. It is possible that this cohort does not always represent baseline participants. Nevertheless, to our knowledge, there is no existing report that ranks with the present study cohort in Japan. There may be a non-response bias. Of 185 survivors in January 2007, 27% did not participate in the survey. When we investigated LUTS in non-responders in the baseline study, their symptom scores were lower than for responders [4].

In conclusion, the present study comprises the first longitudinal community-based survey on LUTS suggestive of BPH and related variables in Japanese men. The findings of the present study show that the IPSS and QoL index deteriorated, PV and PSA level increased, and Qmax decreased with time. However, there were no direct correlations between the change in the IPSS and objective variables such as PV, PSA level and Qmax at baseline, nor their changes.

ACKNOWLEDGEMENTS

The present study was partly supported by grants-in-aid from the Japan Society for the promotion of Science (19591862) and the Gohtaro Sugawara-Memorial Research Fund for Urologic Diseases. The sponsors of the present study had no role with respect to the study design, collection, analysis and interpretation of data.

CONFLICT OF INTEREST

Naoya Masumori and Taiji Tsukamoto receive lecture fees from GSK.

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