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[Mj ORIGINAL ARTICLE 

GossMark Psychiatry ft Psychology 



http://dx.doi.0rg/10.3346/jkms.2014.29.8.1145 • J Korean Med Sci 2014; 29: 1145-1151 



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The Influence of Depression, Anxiety and Somatization on the 
Clinical Symptoms and Treatment Response in Patients with 
Symptoms of Lower Urinary Tract Symptoms Suggestive of 
Benign Prostatic Hyperplasia 



Yong June Yang, 1 Jun Sung Koh, 2 
Hyo Jung Ko, 3 Kang Joon Cho, 2 
Joon Chul Kim, 2 Soo-Jung Lee, 1 
and Chi-Un Pae 1 ' 4 

'Department of Psychiatry, The Catholic University 
of Korea College of Medicine, Seoul; department of 
Urology, The Catholic University of Korea College of 
Medicine, Seoul; department of Psychiatry, Seoul 
Metropolitan Eunpyeong Hospital, Seoul, Korea; 
"Department of Psychiatry and Behavioral Sciences, 
Duke University Medical Center, Durham, NC, USA 

Received: 17 February 2014 
Accepted: 8 May 2014 

Address for Correspondence: 
Chi-Un Pae, MD 

Department of Psychiatry, Bucheon St. Mary's Hospital, 
The Catholic University of Korea College of Medicine, 
327 Sosa-ro, Bucheon 420-717, Korea 
Tel: +82.32-340-7067, Fax: +82.32-340-2255 
E-mail: pae@catholic.ac.kr 

Funding: This work was supported by a grant of the Korean 
Health Technology REtD Project, Ministry of Health Et Welfare, 
Republic of Korea (HI12C0003) and supported partly by Astellas. 



This is the first study to investigate the influence of depression, anxiety and somatization 
on the treatment response for lower urinary tract symptoms/benign prostatic hyperplasia 
(LUTS/BPH). The LUTS/BPH patients were evaluated with the Korean versions of the 
International Prostate Symptom Score (IPSS), the Patient Health Questionnaire-9 (PHQ-9), 
the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the PHQ-1 5. The primary 
endpoint was a responder rate defined by the total score of IPSS (< 7) at the end of 
treatment. The LUTS/BPH severity was significantly higher in patients with depression 
(whole symptoms P = 0.024; storage sub-symptom P= 0.021) or somatization [P= 0.024) 
than in those without, while the quality of life (Q0L) was significantly higher in patients 
with anxiety (P = 0.038) than in those without. Anxious patients showed significantly 
higher proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those without, 
while somatic patients had a trend toward having more non-responders (OR, 2.552, 
P=0.067). Our exploratory results suggest that depression, anxiety and somatization may 
have some influences on the clinical manifestation of LUTS/BPH. Further, anxious patients 
had a lower response to treatment in patients with LUTS/BPH. Despite of limitations, the 
present study demonstrates that clinicians may need careful evaluation of psychiatric 
symptoms for proper management of patients with LUTS/BPH. 

Keywords: Lower Urinary Tract Symptoms; Benign Prostatic Hyperplasia; Depression; 
Anxiety; Somatization; Response 



INTRODUCTION 

Lower urinary tract symptoms (LUTS) manifest multiple do- 
main of clinical symptoms such as storage, voiding and post- 
micturition and are common among older men (1). Of the vari- 
ous etiologies and clinical symptoms associated with LUTS, be- 
nign prostatic hyperplasia (BPH) is considered a primary cause 
and also closely resembles its symptoms, although a clear rela- 
tionship is not fully understood between LUTS and BPH (1-3). 

The underlying pathophysiologies of LUTS/BPH are current- 
ly uncertain but it has been considered a subjective indicator of 
disease, not a confirmative formal diagnosis (4). According to a 
recent huge cross-sectional population-based study, the negative 
effects of LUTS/BPH were prominent across several domains of 
quality of Life (QoL) and on overall perceptions of general health 
status and mental health (5, 6). In addition, the clinical course 
of LUTS/BPH is chronic, recurrent and difficult- to-treat. Accor- 
ding to the recent large catchment area study with 5-yr follow- 



up for natural history of LUTS (n = 5,502) (7), the prevalence of 
LUTS increased from 19% at baseline to 20% at follow-up. In 
particular, only less than half (43%) of those with moderate to 
severe LUTS at baseline remitted or become mild LUTS at fol- 
low-up; most men with severe LUTS at baseline continued to 
have severe LUTS (61.5%) at follow-up. 

However, the treatment response with such medications is 
not satisfactory. A recent treatment guideline also suggests the 
weak efficacy of such medications, where approximately 20%- 
50% reduction in LUTS/BPH symptoms are common after treat- 
ment of monotherapy of a-receptor blockers and 5a-reductase 
inhibitors based on results from a number of short-term and 
long-term clinical trials (8, 9). 

Meanwhile, it was found that the clinical manifestation of 
LUTS/BPH is strongly associated with psychiatric disturbances 
such as depression, anxiety, and stress vulnerability, and im- 
pairments of instrumental activities during daily living in some 
studies (5, 10-17). For instance, the recent large cohort study 



© 2014 The Korean Academy of Medical Sciences. 

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Yang YJ, et al. • Depression, Anxiety and Somatization with Treatment Response for LUTS/BPH 



(14) have also demonstrated the important relationship between 
LUTS/BPH and depression, in which depression was signifi- 
cantly associated with the severity of the diseases as well as it 
also involves in all stages of LUTS. According to a large observa- 
tional, longitudinal, multicenter study (n = 666), a substantial 
proportion (22.6%) of LUTS/BPH patients reported anxiety or 
depression and they also explained a 7% of variance for explain- 
ing the severity of LUTS/BPH. Likewise in a large population- 
based study (EpiLUTS, n = 30,000) (5), approximately 36% and 
30% of men were found to report anxiety and depression, re- 
spectively. Pre-existing study results consistently suggest that 
putative role of psychiatric parameters in the development of 
LUTS/BPH and also proposes that the current treatment for 
LUTS/BPH may not fully ameliorate urinary issues if the under- 
lying psychiatric disturbances are not properly resolved (18). 

Taken together, a high level of psychiatric morbidity has im- 
portant implications for the appropriate management in patients 
with of LUTS/BPH and warrants further in-depth studies in terms 
of potential relationship between psychiatric symptoms and 
treatment reponse in patients with LUTS/BPH (5). However, 
there has been a paucity of clinical data regarding a potential 
influence of such psychiatric disturbances on the treatment 
outcomes in patients with LUTS/BPH till today. 

Therefore, the aim of this study was to investigate the poten- 
tial influences of depression, anxiety and somatisation on the 
treatment response in patients with LUTS/BPH with the use of 
brief, user-friendly and quick but validated rating scales since 
timely and proper measurement of such psychiatric parame- 
ters may help identify individuals more likely to benefit from 
treatment interventions in daily busy routine practice. 

MATERIALS AND METHODS 
Subjects 

Male patients with LUTS/BPH were recruited at an outpatient 
clinic in the Department of Urology at Bucheon St. Mary's Hos- 
pital. 

Principal inclusion criteria included men aged > 40 yr, a clin- 
ical diagnosis of LUTS/BPH was evaluated by medical history, a 
careful physical examination and laboratory tests including 
prostate-specific antigen (PSA) levels. Few exclusion criteria 
were applied because the aims of the study were based on ob- 
servational approach. However, patients who exhibited the fol- 
lowing symptoms were excluded for diagnostic stability: 1) PSA 
level > 10 ng/mL, 2) a history or evidence of prostate cancer by 
prostate biopsy, 3) previous prostatic surgery, 4) any causes of 
LUTS other than BPH (i.e., neurogenic bladder, bladder neck 
contracture, urethral stricture, bladder malignancy, acute or 
chronic prostatitis, or acute or chronic urinary tract infections), 
and 5) speech or language deficits and cognitive dysfunction. 

The study was a 12-week prospective observational design in 



a naturalistic treatment setting. Alpha-blockers, 5-alpha-reduc- 
tase inhibitors or combination of both were the primary treat- 
ment utilised for the patients during the study. Throughout the 
study period, patients remained on the same medication and 
the same dosage as was given at the time of enrolment. 

Rating scales 

All the rating scales were examined at baseline and week 12. 
The Korean versions of the International Prostate Symptom 
Score (IPSS) for severity of LUTS/BPH (19), the Patient Health 
Questionnaire-9 (PHQ-9) for depression (20, 21), the Patient 
Health Questionnaire-15 (PHQ-15) for somatization (22, 23) 
and the 7-item Generalized Anxiety Disorder Scale (GAD-7) 
(24) for anxiety, were utilized in the study. The criteria for de- 
pression ( > 5 on PHQ-9) (20), anxiety ( > 5 on GAD-7) (24) and 
somatisation (> 5 on PHQ-15) (22) were defined by previous 
studies suggested. 

Treatment outcomes 

The primary endpoint of the study was a responder rate defined 
by the total score of IPSS ( < 7) at the end of treatment (week 
12). The 7 point response criterion was chosen since the IPSS 
total score of 7 indicates no or mild symptoms of LUTS/BPH. 

Secondary endpoints included the changes in total scores 
and three sub-scores on the storage, obstruction, and QoL do- 
mains of the IPSS from baseline to week 12. Other responder 
analyses by different criteria included as follows: 1) > 5 points 
and 2) > 30% decrease from baseline to week 12 in IPSS total 
score from baseline to week 12 (25, 26). In LUTS/BPH clinical 
trials, regarding point decrease with IPPS total score, the 4 to 6 
points decline was common and 3 points decrease was propos- 
ed to be the minimum for clinical benefit (26). Regarding % im- 
provement of IPSS total score from baseline, 25% and 30% re- 
ductions in IPSS total score were mostly utilized. However, none 
of point decrease or % reduction in IPSS total score has been 
validated as established response criteria, they were usually 
empirically used by individual research group. Hence, we have 
also empirically chosen the 5 point decrease and 30% improve- 
ment of IPSS total score as another potential response criteria. 

Statistical analyses 

Demographic variables were compared by the presence of de- 
pression, anxiety and somatization using Student's Mest, a chi- 
square test with Yate's correction, or Fisher's test, as appropri- 
ate. To investigate the influence of each clinical parameter on 
various treatment outcomes, changes of individual rating scales 
from baseline to week 12 were analyzed using an analysis of co- 
variance (ANCOVA) controlling for age, duration of disease and 
type of medication. To analyze responders as defined a priori, 
Fisher's exact tests were conducted. Odds ratio (OR) with 95% 
confidence intervals (CIs) was also utilized for the responder 



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analysis as well. 

Statistical significance was two-tailed and set at P < 0.05 and 
there was no adjustment for multiple comparisons because the 
sample size was relatively small. With these statistical parame- 
ters and after adjusting with covariates, the power of the sample 
to detect a medium effect size (d = 0.5) was 0.6108, which cor- 
responds to a difference of 2.6 in the mean changes of IPSS total 
scores between patients with depression and those without. All 
statistical analyses were conducted using the NCSS 2007® and 
PASS 2008® software (Kaysville, Utah, USA). 

Ethics statement 

The institutional review board of Bucheon St. Mary's Hospital 
approved this study (IRB No. HC1 1OISE0004). Written informed 
consent was obtained from all participants. 

RESULTS 

Baseline demographic characteristics 

Ninety three patients participated in the study. The mean age of 
the whole population was approximately 62 (61.7 ± 8.0) yr, and 
the majority of patients were married. More than half of patients 
exhibited comorbid medical diseases. The mean total score on 
the IPSS among all groups was approximately 17, indicating a 



moderate severity of LUTS/BPH symptoms. The mean volume 
of prostate (PV) and peak flow rate (Qmax) were 36.8 ±15.5 mL 
and 13.3 ±1.9 mL/sec, respectively; however, PVand Qmax were 
not significantly different by presence of depression, anxiety 
and somatization (Table 1). In addition, the PV and Qmax were 
not significantly different as criteria of responders and non-re- 
sponders: 1) 33.2 ± 16.2 mL vs. 38.3 ± 15.0 mL and 13.5 ± 1.3 
mL/sec vs. 13.3 ±2.1 mL/sec, respectively, by IPSS at endpoint 
(< 7); 2) 38.2 ± 15.3 mL vs. 35.6 ± 15.8 mL and 13.1 ± 1.7 mL/ 
sec vs. 13.5 ±2.1 mL/sec, respectively, by IPSS decrease from 
baseline ( > 5) and 3) 36.6 ± 14.2 mL vs. 36.9 ± 16.5 mL and 13.4 
± 1.3 mL/sec vs. 13.3 ± 2.3 mL/sec, respectively, by IPSS decrease 
from baseline ( > 30%). 

Depression subgroup 

There were no group differences in demographic variables such 
as education level, family history of LUTS/BPH, economic sta- 
tus, comorbidity, alcohol history, smoking history, or marriage 
status between the two groups (data available on request). The 
LUTS/BPH total score was significantly higher in patients with 
depression than those without (18.5 vs. 15.3, P = 0.046). In the 
sub-symptom analysis, the storage sub-symptom was also sig- 
nificantly higher in patients with depression than in those with- 
out (7.6 vs. 5.8, P = 0.021). However, all the treatment outcomes 



Table 1 . Baseline characteristics of the subjects (n = 93) 





Depression 


Anxiety 


Somatization 




Presence (n = 35) 


Absence (n = 58) 


Presence (n = 38) 


Absence (n = 55) 


Presence (n = 46) 


Absence (n = 47) 


Age (yr) 


61.9 ± 7.9 


61.3 ± 8.1 


62.1 ± 8.3 


61.5 ± 7.8 


62.5 ± 8.0 


61.0 ± 7.9 


Duration of illness 


11.9 ± 10.6 


14.7 ± 17.8 


16.9 ± 11.7 


15.0 ± 14.3 


13.9 ± 16.7 


13.4 ± 14.3 


(months) 














IPSS total 


18.5 ± 6.9 


15.3 ± 7.9* 


17.7 ± 6.5 


15.6 ± 8.3 


18.3 ± 7.3 


14.7 ± 7.6* 


IPSS-Obs 


10.9 ± 4.5 


9.4 ± 5.4 


10.7 ± 4.6 


9.5 ± 5.4 


11.0 ± 4.8 


8.9 ± 5.3* 


IPSS-Sto 


7.6 ± 3.4 


5.8 ± 3.7 § 


7.1 ± 3.1 


6.1 ± 3.9 


7.3 ± 3.5 


5.8 ± 3.6* 


IPSS-QoL 


3.8 ± 1.4 


3.3 ± 1.5 


3.8 ± 1.3 


3.2 ± 1.6" 


3.7 ± 1.4 


3.2 ± 1.5 


PV (mL) 


38.0 ± 15.3 


36.1 ± 15.7 


40.0 ± 14.9 


34.6 ± 15.6 


38.6 ± 16.6 


35.1 ± 14.3 


Qmax (mL/sec) 


13.2 ± 1.8 


13.4 ± 2.0 


13.2 ± 1.7 


13.4 ± 2.1 


13.2 ± 1.7 


13.5 ± 2.1 


Medication 














AB alone 


18(51.4) 


23 (39.7) 


17(44.7) 


24 (43.6) 


22 (47.8) 


19(40.4) 


5ARI alone 


12(34.3) 


22 (37.9) 


15(39.5) 


19(34.5) 


18(39.1) 


16(34.0) 


Combination 


5(14.3) 


13(22.4) 


6(15.8) 


12(21.8) 


6(13.0) 


12(25.5) 



Data represent mean ± standard deviation or number (%). *P= 0.046; *P = 0.024; *trend toward a significance; § P= 0.021; "P= 0.038. IPSS, International Prostate Symp- 
tom Score; Obs, obstruction; sto, storage; QoL, quality of life; AB, Alpha-blockers; 5ARI, 5-alpha-reductase inhibitors; combination = AB plus 5 ARI; Qmax, peak flow rate; PV, 
prostate volume. 



Table 2. The mean changes in total and sub-scores on IPSS during the study (n = 93)* 





Depression 


Anxiety 


Somatization 




Presence (n = 35) 


Absence (n = 58) 


Presence (n = 38) Absence (n = 55) 


Presence (n = 46) 


Absence (n = 47) 


IPSS total 


-4.6 ± 5.4 


-4.0 ± 5.8 


-3.6 ± 5.2 -4.7 ± 6.0 


-4.3 ± 4.9 


-4.1 ± 6.3 


IPSS-Obs 


-2.9 ± 3.9 


-2.6 ± 4.0 


-2.3 ± 3.7 -2.9 ± 4.1 


-3.0 ± 3.7 


-2.4 ± 4.2 


IPSS-Sto 


-1.7 ± 2.7 


-1.4 ± 2.5 


-1.2 ±2.6 -1.7 ±2.5 


-1.4 ± 2.2 


-1.7 ± 2.9 


IPSS-QoL 


-1.1 ± 1.3 


-0.7 ± 1.3 


-0.9 ±1.2 -0.9 ±1.4 


-0.8 ± 1.2 


-1.0 ± 1.5 



Data represent mean ± standard deviation. 'Analysis of Covariance, all P values are not significant. IPSS, International Prostate Symptom Score; Obs, obstruction; sto, storage; 
QoL, quality of life. 



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Yang YJ, et al. • Depression, Anxiety and Somatization with Treatment Response for LUTS/BPH 



Table 3. The proportion of responders by different criteria in the study (n = 93)* 



Depression Anxiety Somatization 

Response criteria 

Presence (n = 35) Absence (n = 58) Presence (n = 38) Absence (n = 55) Presence (n = 46) Absence (n = 47) 



< 7 in IPSS* 



Response 


7 (20.0) 


20 (34.5) 


6(15.8) 


21 (38.2) 


9(19.6) 


18(38.3) 


Nonresponse 


28 (80.0) 


38 (65.5) 


32 (84.2)* 


34 (61.8) 


37 (80.4) 5 


29 (61.7) 


5 points responder" 














Response 


18(51.4) 


24 (41 .4) 


15(39.5) 


27 (49.1) 


22 (47.8) 


20 (42.6) 


Nonresponse 


17(48.6) 


34 (58.6) 


23 (60.5) 


28 (50.9) 


24 (52.2) 


27 (57.4) 


30% responder 1 














Response 


17(48.6) 


24 (41 .4) 


15(39.5) 


26 (47.3) 


19(41.3) 


22 (46.8) 


Nonresponse 


18(51.4) 


34 (58.6) 


23 (60.5) 


29 (52.7) 


27 (58.7) 


25 (53.2) 



Data represent number (%). 'Fisher's Exact test; *Response defined by a total score of < 7 on the IPSS at week 12; *Odds ratio (OR) for nonresponse = 3.294 (95% 
CIs = 1.073-10.530), chi-square = 5.410, P= 0.022; § trend toward a significant difference, OR for nonresponse = 2.552 (95% CIs = 0.913-7.255), chi-square = 3.959, 
P= 0.067; "Response defined by 5 or more decrease in IPSS from baseline; 'Responder defined 30% or more decrease in IPSS from baseline at week 12; 95% CIs, 95% con- 
fidence intervals. IPSS, International Prostate Symptom Score. 



were not different between the two groups (Tables 2, 3). 
Anxiety subgroup 

There were no group differences in demographic variables such 
as education level, family history of LUTS/BPH, economic sta- 
tus, comorbidity, alcohol history, smoking history, or marriage 
status between the two groups (data available on request). The 
LUTS/BPH total score was not different between the two groups. 
QoL sub-score was significantly higher in patients with anxiety 
(3.8 vs. 3.2, P = 0.038) than in those without. Anxious patients 
showed significantly higher proportion of non-response (OR, 
3.294, P = 0.022) than those without in primary endpoint analy- 
sis (Tables 2, 3). 

Somatization subgroup 

There were no group differences in demographic variables such 
as education level, family history of LUTS/BPH, economic sta- 
tus, comorbidity, alcohol history, smoking history, or marriage 
status between the two groups (data available on request). The 
LUTS/BPH total score was significanuy higher in patients with 
somatization than in those without (f 8.3 vs. 14.7, P = 0.024). In 
addition, obstruction and storage sub-scores were in a trend to- 
ward a significant difference between the two groups (11.2 vs. 
8.9 and 7.3 vs. 5.8, respectively, P = 0.050 and P = 0.050, respec- 
tively). There were no differences in all the treatment outcomes, 
although a trend toward a significant difference was found in 
primary endpoint analysis (P = 0.067) (Tables 2, 3). 

DISCUSSION 

Our preliminary results suggest that depression, anxiety and 
somatization may have partly influences on the clinical mani- 
festation of LUTS/BPH. Further, anxious patients had a lower 
response to treatment in patients with LUTS/BPH. The most 
strength of our study is to assess the relationship of depression, 
somatisation and anxiety with treatment response in patients 



with LUTS/BPH for the first time, especially with the use of sim- 
ple, quick, reliable, well-validated, and self-administered rating 
scales which are easy to administer and interpret even in busy 
routine practice. However, the PV and Qmax were not signifi- 
cantly different by presence or absence of depression, anxiety, 
and somatization. 

A common neurochemical underpinning maybe speculated 
to be attributable to depression/anxiety/somatization and blad- 
der function. A compelling association between central and 
peripheral serotonin (5-HT)/norepinephrine (NE) systems and 
lower urinary tract function has been consistently proposed 
(27). In fact, duloxetine (serotonin/norepinephrine reuptake 
inhibitor, SNRI) has been approved for the treatment of urinary 
incontinence in Europe in 2004. It has been found to increases 
bladder capacity and urethral sphincter electromyographic ac- 
tivity in an animal model, which is mediated by increases in ex- 
tracellular 5-HT or NE (28). In addition, the reduction of 5-HT 
developed urinary frequency and caused detrusor over-activity, 
which was successfully reversed by fluoxetine the selective se- 
rotonin reuptake inhibitor (SSRI) (29). Other studies (30) also 
suggest that the role of 5-HT in urinary function; 5-HT reuptake 
transporter knockout mice (-/-) demonstrated a bladder dys- 
function, characterized by significant increases in the frequen- 
cy of spontaneous non-voiding bladder contractions and de- 
creases in voiding volume. It was also found that the predomi- 
nant effect of NE release from sympathetic nerve terminals is 
on urethral contraction mediated through al- and a2-adrenergic 
receptors (31-33). Therefore antidepressants such as SNRIs as 
well as SSRIs could be considered to enhance urine storage by 
decreasing bladder contractility and increasing outlet resistance. 
In addition, the crucial role of serotonin and norepinephrine 
has been very-well known in the development and manage- 
ment of depression, anxiety and somatization, which are effec- 
tively controlled by SNRIs (34). In fact, depression, anxiety and 
somatisation have been found to impact on self-perception, 
treatment compliance, coping strategies and clinical status in a 



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various mental health and physical diseases. Taken together, 
we may deliberately speculate that depression/ anxiety/somati- 
zation and LUTS are all linked with major neurotransmitters, 
5-HT and NE, and that thereby these psychiatric symptoms 
may play a role in the development of clinical symptoms and 
treatment outcomes in patients with LUTS/BPH. 

Differential associations between psychiatric symptoms and 
LUTS were found in male patients in a previous study (5), where 
depression was more associated with storage and post-micturi- 
tion in male patients (5). Likewise the present study also found 
the association of storage symptoms and depression, support- 
ing the previous finding that depressed patients may have more 
bother in urinary frequency. 

Many previous studies have replicated lower QoL in patients 
with LUTS/BPH were prominent across several domains of qual- 
ity of Life (QoL) and on overall perceptions of general health 
status and mental health, especially accompanied by depres- 
sion/anxiety. Likewise, we also found a significant association 
of anxiety with QoL in the present study, although depression 
did not show such relationship. This slight discrepancy may be 
caused by different sample characteristic, sample size, different 
measurement of depression and so on. Our findings partly sup- 
port the pre-existing study results. 

The presence of anxiety and improvement of anxiety was sig- 
nificantly associated with the non-response in the present study, 
indicating that clinicians may benefit in expectation of future 
response in clinical practice if they know the level or improve- 
ment of anxiety. Our results are in line with the previous find- 
ings that anxiety may be involved as a risk factor in the severity 
and progression of LUTS/BPH (5, 16, 35). 

An increasing evidence suggests the possibility that for some 
patients with LUTS/BPH (18, 35), CP/CPPS (36, 37) and urinary 
incontinence (38), urinary symptoms could be part of a soma- 
tizing process and requires further consideration (35). In fact, 
previous studies have consistently reported that the worse phys- 
ical health ratings are significantly associated with more bother 
in patients with LUTS/BPH, indicating that measures of urinary 
bother capture somatic distress should be necessary and that 
treating LUTS/BPH alone may not completely ameliorate uri- 
nary bother if underlying such somatic concerns are not addre- 
ssed (35). 

Our preliminary study has a number of limitations and also 
implicates future study direction. First, the small sample size 
may be insufficient to detect such relationship between per- 
sonality and symptom severity of LUTS/BPH. Currently, there 
are no large and unselected population-based studies that have 
utilised the PHQ-9, PHQ-15, and GAD-7 on patients with LUTS/ 
BPH, and thus, the current results are entirely exploratory. The 
use of brief self- rating scales may be one of strength to be uti- 
lized in busy clinical practice but also could be a critical limita- 
tion; we propose to use of both subjective and objective rating 



scale to verify depression, anxiety and somatization as well as 
including some assessment of current burden of stress. The 
study period was only 3 months and thus we do not know the 
long-term effects of such psychiatric parameters on the clinical 
course and treatment response. An additional dilemma for clin- 
ical researchers is whether to correct for multiple comparisons. 
We did not perform multiple comparison correction in the pres- 
ent study due to the nature and small sample size of the study. 
The Bonferroni correction is the most popular way to correct 
for the multiple testing issue, but its utility may depend on the 
nature of the study. According to Streiner and Norman (39), 
correction of multiple testing can be waived if a small number 
of hypotheses have been stated a priori or if the purpose of the 
study is exploratory (preliminary), and this is also in agreement 
with the assertions of other researchers (40). Finally, the sample 
was only recruited in one teaching hospital and may not repre- 
sent the general LUTS/BPH population. 

In conclusion, the present study preMminarily demonstrates 
that clinicians may need careful evaluation of depression, anxi- 
ety and somatization issues for the proper management of pa- 
tients with LUTS/BPH, despite study limitations. Subsequent 
studies with adequately-powered and better design may be cru- 
cial to validate and support the present exploratory study find- 
ings. 

DISCLOSURE 

The authors have no conflicts of interest to disclose. 
ORCID 

Yong June Yang http://orcid. org/0000-0003-0135-0080 
Jun Sung Koh http://orcid.org/0000-0001-7432-4209 
Hyo JungKo http://orcid.org/0000-0002-9034-1524 
Kang Joon Cho http://orcid.org/0000-0002-5305-901X 
Joon Chul Kim http://orcid. org/0000-0002-401 9-620X 
Soo-Jung Lee http://orcid.org/0000-0002-1299-5266 
Chi-Un Pae http://orcid. org/0000-0002-6774-941 7 

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