Medicine

SYSTEMATIC REVIEW AND META-ANALYSIS

The Association Between Metabolic Syndrome and

Characteristics of Benign Prostatic Hyperplasia
A Systematic Review and Meta-Analysis
Jian-Ye Wang, MD, PhD, Yan-Yan Fu, MD, PhD, and De-Ying Kang, MD

Abstract: The purpose of this systematic review was to examine the A total of 158 potentially relevant studies were identified, and 8 were
association of metabolic syndrome (MS) with measures of benign included in the meta-analysis. The 8 studies included in the meta-
prostatic hyperplasia (BPH) including prostate growth rate, prostate analysis contained a total of 3093 BPH patients, wherein 1241 had MS
volume, International Prostate Symptom Score (IPSS), prostate-specific and 1852 did not have MS. BPH patients with MS had a significantly
antigen (PSA) level, and maximal flow rate. higher prostate growth rate (pooled mean difference ¼ 0.67 mL/y,
Medline, Cochrane CENTRAL, EMBASE, CBM, and Google P < 0.001) and larger prostate volume (pooled mean differen-
Scholar databases were searched until March 23, 2015 using combi- ce ¼ 6.8 mL, P ¼ 0.010) than the BPH patients without MS. There
nations of the keywords benign prostate hyperplasia/BPH, metabolic was no significant difference in IPSS score (pooled mean
syndrome, total prostate volume, prostate growth rate, prostate specific difference ¼ 1.58, P ¼ 0.202) or maximal flow rate (pooled mean dif-
antigen, International Prostate Symptom Score/IPSS, maximal flow ference ¼ 1.41 mL/s, P ¼ .345) between BPH patients with and with-
rate. Cohort or case–control studies of patients with BPH and MS that out MS. A borderline nonsignificant difference in PSA (pooled mean
reported quantitative outcomes were included. The pooled mean differ- difference ¼ 0.24 ng/mL, P ¼ 0.056) was noted between BPH patients
ences of the outcome measures were compared between patients with with and without MS.
and without MS. The results of this meta-analysis are consistent with literature
indicating that BPH patients with MS have a higher prostate growth
rate and larger prostate volume than those without MS; however, further
study is necessary to determine the association of BPH and metabolic
Editor: Giandomenico Roviello.
Received: November 12, 2015; revised and accepted: March 9, 2016.
disorder elements and the potential risk of disease progression in BPH
From the Department of Urology, Beijing Hospital, Ministry of Health (J- patients with MS.
YW); MSD China, Medical Affairs Department, Beijing Office, Beijing (Y-
YF); and Department of Evidence Based Medicine and Clinical (Medicine 95(19):e3243)
Epidemiology (D-YK); West China Hospital, Sichuan University, Chengdu
China (D-Y K). Abbreviations: BMI = body mass index, BPH = benign prostatic
Correspondence: De-Ying Kang, Department of Evidence Based Medicine hyperplasia, CI = confidence interval, ED = erectile dysfunction,
and Clinical Epidemiology, West China Hospital, Sichuan University,
Chengdu 610041, China (e-mail: [email protected]).
HDL-C = high-density lipoprotein cholesterol, HOMA-IR =
Supplemental Digital Content is Available for this Article. homeostatic model assessment of insulin resistance, IPSS =
The medical writing and editorial assistance provided by Dr. Richard International Prostate Symptom Score, LUTS = lower urinary
Sandore, MedCom Asia, Inc was funded by MSD China. tract symptoms, MS = metabolic syndrome, PSA = prostate specific
The authors initiated the concept for the meta-analysis and are responsible
for the content of the manuscript.
antigen.
Where there was uncertainty regarding eligibility, a third reviewer (Dr.
Namis Lai, MD, of MedCom Asia) was consulted.
J-YW contributed to conceiving and study design, providing substantive
suggestions for revision or critical review, reviewing, and approving final INTRODUCTION

B
version of the article, and all aspects of the work in ensuring that enign prostatic hyperplasia (BPH), characterized by enlar-
questions related to the accuracy or integrity of any part of the work gement of the prostate gland and narrowing of the urethra,
are appropriately investigated and resolved.
D-YK contributed to critical review, final version of the article, and all affects >50% of men older than 60 years and the majority older
aspects of the work in ensuring that questions related to the accuracy or than 80 years, and is a major cause of lower urinary tract
integrity of any part of the work are appropriately investigated and symptoms (LUTS).1,2 LUTS can be obstructive and/or irritative,
resolved. and can significantly affect quality of life.1,2 BPH is the result of
Y-YF, the medical manager of MSD, contributed to conceiving and study
design, interpreting the results, providing substantive suggestions for a nonmalignant proliferation of cells in the prostate gland, and
revision or critical review, reviewing and approving final version of the although the etiology of the proliferation is not well understood,
article, and all aspects of the work in ensuring that questions related to known factors associated with BPH are aging and androgen
the accuracy or integrity of any part of the work are appropriately metabolism.3 Recent evidence has also suggested that metabolic
investigated and resolved.
J-YW, Y-YF (the medical manager of MSD), and D-YK had no relevant disorders, including hyperinsulinemia, dyslipidemia, and
conflict of interest in the work under consideration for publication, obesity may play a role in the development of prostate hyper-
relevant financial activities outside the submitted work, intellectual plasia.4– 7
property, and relationships not covered above. Metabolic syndrome (MS) is a cluster of medical con-
Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
This is an open access article distributed under the Creative Commons ditions including hypertension, impaired glucose metabolism,
Attribution-NonCommercial-NoDerivatives License 4.0, where it is abdominal obesity, hypertriglyceridemia, and low high-density
permissible to download, share and reproduce the work in any medium, lipoprotein cholesterol (HDL-C).8 The underlying feature of
provided it is properly cited. The work cannot be changed in any way or MS is insulin resistance, and MS is associated with an increased
used commercially.
ISSN: 0025-7974 risk of type 2 diabetes mellitus and cardiovascular disease.8
DOI: 10.1097/MD.0000000000003243 Similar to BPH, the prevalence of MS increases with age.9

Medicine  Volume 95, Number 19, May 2016 www.md-journal.com | 1

Wang et al Medicine  Volume 95, Number 19, May 2016

Furthermore, recent evidence is suggesting a link between MS pooled estimates of the primary and secondary outcomes.
and prostatic hyperplasia and LUTS.5,10– 13 In contrast with Publication bias was not evaluated in this study because there
results from the United States and European countries, results were only 3 studies included for the primary outcome (prostate
from Asian populations have been inconsistent.1 One study growth rate), which is insufficient to detect funnel plot asym-
indicated that MS was not clearly correlated with LUTS/BPH in metry.20 All analyses were performed with Comprehensive
Korean men in their 50s,1 whereas the results of another study Meta-Analysis software, version 2.0 (Biostat, Englewood, NJ).
indicated that MS was associated with an increased total volume
and annual prostate growth rate.14 A recent meta-analysis ETHICS
indicated that patients with MS have a higher total prostate
This study did not involve human subjects, so informed
volume than those without MS, yet International Prostate
consent was not required. In addition, no approval was required
Symptom Scores (IPSS) were not different between those with
from an institutional review board.
and without MS.15
As there are a number of different measures of determining
BPH, the purpose of this meta-analysis was to examine the RESULTS
association of MS with measures of BPH including prostate
growth rate, prostate volume, IPSS, prostate-specific antigen Literature Search and Study Characteristics
(PSA) level, and maximal flow rate. A flow diagram of study selection is shown in Supple-
mental Figure 1, http://links.lww.com/MD/A920. A total of
158 potentially relevant studies were identified, and 118
MATERIALS AND METHODS remained after duplicates were excluded. After screening by
Literature Search and Study Selection title and abstract, 31 articles were excluded, the reasons for
which are shown in Supplemental Figure 1, http://links.lww.-
This systematic review and meta-analysis was performed
com/MD/A920. Nine full-text articles were assessed for eligi-
in accordance with MOOSE guidelines.16 Medline, Cochrane,
bility, and of these, 8 were included in the meta-analysis.21 – 28
EMBASE, Google Scholar databases, and CBM were searched
The study by Aktas et al29 was included in the qualitative
from inception until March 23, 2015 using combinations of the
synthesis, but did not include measures appropriate for the
keywords: benign prostate hyperplasia/BPH, metabolic syn-
meta-analysis.
drome, total prostate volume, prostate growth rate, prostate
The characteristics of the included studies were summar-
specific antigen, International Prostate Symptom Score/IPSS,
ized in Table 1. The 8 studies included in the meta-analysis
maximal flow rate. Inclusion criteria for the analysis were:
contained a total of 3093 BPH patients, wherein 1241 had MS
cohort or case-controlled studies; patients had BPH with or
and 1852 did not have MS. The primary and secondary out-
without LUTS and were older than 18 years; compared patients
comes of the included studies are summarized in Supplemental
with and without MS; quantitative outcomes of interest were
Table 1. http://links.lww.com/MD/A920.
reported. Letters, comments, editorials, case reports, proceed-
ings, and personal communications were excluded, as were
studies in which no quantitative outcome was reported. Refer- Quality Assessment
ence lists of relevant studies were hand-searched. Searches were Results of the Newcastle-Ottawa scales assessment of the
conducted by 2 reviewers, and a third reviewer was consulted included studies are shown in Table 1. Six studies had a total
for resolution of disagreements. score of 8 points, and 3 studies a total score of 7 points,
The following information/data were extracted from stu- indicating that the overall quality of the included studies
dies that met the inclusion criteria: the name of the first author, was acceptable.
year of publication, number of patients in each group, age, BMI,
IPSS, and quantitative outcomes. Primary Outcome (Prostate growth Rate)
Three studies reported prostate growth rate data.25,27,28 No
Quality Assessment significant heterogeneity was observed (Cochran Q ¼ 3.6,
The Newcastle-Ottawa scale was used to assess the quality P ¼ 0.167; I2 ¼ 44.1%), and thus a fixed-effects model of analysis
of the included studies.17 Briefly, the instrument contains 8 was performed. BPH patients with MS had a significantly higher
items categorized into 3 dimensions: selection, comparability, prostate growth rate than the BPH patients without MS (pooled
and exposure (outcome). A point system is used for a semi- mean difference ¼ 0.67 mL/y, P < 0.001; Figure 1 A). The
quantitative assessment of study quality. pooled mean differences of prostate growth rate with each of
the studies removed were similar (range, 0.55–0.68 mL/y), and
Outcome Measures and Data Analysis remained statistically significant (all, P < 0.001), indicating good
reliability in the pooled estimate (Figure 1B).
The primary outcome was the association of prostate
growth rate and MS, and secondary outcomes were the associ-
ations of prostate volume, PSA level, IPSS, and maximal flow Prostate Volume
rate with MS. Data reported as median and range were con- All 8 studies reported prostate volume data.21– 28 Signifi-
verted to mean and standard deviation.18 Pooled mean differ- cant heterogeneity was observed (Cochran Q ¼ 70.6, P < 0.001;
ences were compared between groups. Heterogeneity among I2 ¼ 90.1%), and thus a random-effects model of analysis was
the studies was assessed by the Cochran Q and the I2 statistic.19 performed. BPH patients with MS had a significantly larger
If either the Q statistic value of P was <0.1 or I2 was >50%, a prostate volume than BPH patients without MS (pooled mean
random-effects model of analysis (DerSimonian-Laird method) difference ¼ 6.8 mL, P ¼ 0.010; Figure 2A). The pooled mean
was used. Otherwise, a fixed-effects model (Mantel-Haenszel differences of prostate volume with each of the studies removed
method) was used. Sensitivity analyses based on the leave-one- were similar (range, 5.27–9.27 mL), indicating acceptable
out approach were performed to evaluate the robustness of the reliability in the pooled estimate (Figure 2B).

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 TABLE 1. Basic Characteristics of Included Studies
Medicine

Copyright
First Author Definition of Imaging Techniques Newcastle-


#
(Publication Metabolic for Number of Ottawa
2
Year) Population Study Design Syndrome Prostate Volume Group Patients Age, y BMI, kg/m IPSS Scale

Gacci et al Italy Prospective NCEP-ATP III43 Ultrasound With MS 140 69.7  7.4 27.4  3.5 20.0  5.7 8
(2015)21
Without MS 238 68.5  8.8 25.7  2.3 20.5  4.8
Cyrus et al Iran Cohort WHO criteria44 Transrectal With MS 47 62.5  9.6 NR 16.95  8.54 8
(2014)22 ultrasonography
Without MS 53 NR 16.81  7.01
De Nunzio et al Italy Cohort NCEP-ATP III Transrectal With MS 103 68.8  6.3 29.8  4.3 9.7  6.8 8
(2014)23 ultrasonography
Without MS 328 65.9  8.4 26.5  3.3 9.6  7.2
Zhang et al China Cohort NCEP-ATP III Transrectal With MS 222 76.93  5.85 26.18  2.78 11.18  7.52 8
(2014)24 ultrasonography
Without MS 179 77.75  5.78 23.45  2.50 11.20  7.96
Volume 95, Number 19, May 2016

Pan et al China Retrospective NCEP-ATP III Ultrasonography With MS 418 68.44  9.82 28.20  2.16 24.80  3.93 7
(2014)25 cohort
Without MS 634 71.24  5.93 24.14  1.20 18.58  2.87
Gacci et al Italy Retrospective IDF and AHA/ Transrectal With MS 86 69  7.4 27.4  3.5 22.5  5.7 7
(2013)26 NHLBI45 ultrasonography

2016 Wolters Kluwer Health, Inc. All rights reserved.

Without MS 185 68  7.5 25.4  3.6 20.9  5.7
Aktas et al29 Turkey Cohort NCEP-ATP III Transrectal and With MS 33 60.41  6.75 NR IPSS 0–7: 14 8

(2011) transabdominal
ultrasonography
IPSS 8–19: 16
IPSS 20–35: 3
Without MS 73 NR IPSS 0–7: 19
IPSS 8–19: 50
IPSS 20–35: 4
Cao et al Chinese Retrospective Modified IDF46 Transabdominal With MS 187 70.14  8.59 26.19  2.82 23.10  4.44 7
(2010)27 cohort ultrasonography
Without MS 195 71.79  9.02 23.25  2.78 20.41  4.98
Ozden et al Turkey Prospective NCEP ATP III Transrectal With MS 38 59 (50–83)y 28.7 (21.2–36.7)y 22 (10–32)y 8
(2007)28 ultrasonography
y y y
Without MS 40 60 (50–72) 25.4 (19.5–31.9) 20 (10–33)

AHA/NHLBI ¼ American Heart Association/National Heart, Lung, and Blood Institute, BMI ¼ body mass index, IDF ¼ International Diabetes Foundation, IPSS ¼ International Prostate Symptom
Score, MS ¼ metabolic syndrome, NCEP ATP III ¼ National Cholesterol. Education Program Adult Treatment Panel III, NR ¼ not reported, WHO ¼ World Health Organization.

The study by Aktas et al. was retained for systematic review only, as its outcomes were not appropriate for the meta-analysis.
y
Data are presented as median (full range). All other data are presented as mean  standard deviation.

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Metabolic Syndrome and BPH
Wang et al Medicine  Volume 95, Number 19, May 2016

FIGURE 1. Meta-analysis for prostate growth rate. (A) Pooled estimate. (B) Sensitivity analysis.

PSA was performed. BPH patients with and without MS had a

Six studies reported PSA data.21,23–25,27,28 Significant borderline nonsignificant difference in PSA (pooled mean
heterogeneity was observed (Cochran Q ¼ 11.8, P ¼ 0.038; difference ¼ 0.24 ng/mL, P ¼ .056; Figure 3A). The pooled
I2 ¼ 57.5%), and thus a random-effects model of analysis mean differences of PSA with each of the studies removed

FIGURE 2. Meta-analysis for prostate volume. (A) Pooled estimate. (B) Sensitivity analysis.

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Medicine  Volume 95, Number 19, May 2016 Metabolic Syndrome and BPH

FIGURE 3. Meta-analysis for prostatic specific antigen. (A) Pooled estimate. (B) Sensitivity analysis.

were similar (range, 0.15–0.32 ng/mL), which indicated an patients with and without MS, and the mean differences of
acceptable reliability in the pooled estimate (Figure 3B). prostate volume showed no obvious heterogeneity (Q ¼ 3.2,
df ¼ 3, P ¼ 0.360; I2 ¼ 6.7%); thus, a fixed-effects model was
IPSS used. The pooled estimate showed that patients with MS had
higher prostate volume than those without MS (pooled mean
All 8 studies reported IPSS data.21–28 Because significant
difference ¼ 11.96, 95% confidence interval [CI]: 10.94–12.98,
heterogeneity was observed between studies (Cochran
P < .001). Three studies from Europe21,23,26 reported prostate
Q ¼ 250.8, P < 0.001; I2 ¼ 97.2%), a random-effects model
volumes for patients with and without MS, and the mean
of analysis was performed. There was no significant difference
differences of prostate volume showed obvious heterogeneity
in IPSS score between BPH patients with and without MS
(Q ¼ 5.9, df ¼ 2, P ¼ 0.053; I2 ¼ 66.1%); thus, a random-effects
(pooled mean difference ¼ 1.58, P ¼ .202; Figure 4A). The
model was used. The pooled estimate showed no significant
pooled mean differences of IPSS with each of the studies
difference in prostate volume between patients with and without
removed were similar and remained statistically nonsignificant
MS (Figure 6A).
(all, P > 0.05), which indicated a good reliability in the pooled
Three studies from Asia24,25,27 reported PSA for patients
estimate (Figure 4B).
with and without MS, and the mean differences of PSA showed
minor heterogeneity (Q ¼ 3.9, df ¼ 2, P ¼ 0.146; I2 ¼ 48.1%);
Maximal Flow Rate thus, a fixed-effects model was used. The pooled estimate
Four studies reported maximal flow rate data.21,24–26 showed that patients with MS had higher PSA than those
Because significant heterogeneity was observed between studies without MS (pooled mean difference ¼ 0.17, 95% CI: 0.00–
(Cochran Q ¼ 297.8, P < 0.001; I2 ¼ 99.0%), a random-effects 0.34, P ¼ 0.044). Two studies from Europe21,23 showed obvious
model of analysis was performed. There was no difference in heterogeneity (Q ¼ 7.9, df ¼ 1, P ¼ 0.005; I2 ¼ 87.3%); thus, a
maximal flow rate between BPH patients with and without MS random-effects model was used. The pooled estimate showed
(pooled mean difference ¼ 1.41 mL/s, P ¼ 0.345; Figure 5A). no significant difference in PSA between patients with and
The pooled mean differences of maximal flow rate with each of without MS (Figure 6B).
the studies removed were similar (range, 1.92 to 0.27 mL/s) Four studies from Asia22,24,25,27 and 3 from Europe21,23,26
and remained statistically nonsignificant (all, P > 0.05), indicat- reported IPSS data, and obvious heterogeneity was present in
ing good reliability in the pooled estimate (Figure 5B). both groups (Asia: Q ¼ 104.7, P < 0.001, I2 ¼ 97.1%; Europe:
Q ¼ 5.2, P ¼ 0.075; I2 ¼ 61.4%); thus, random-effects models
Subgroup Analysis By Region (Asia And Europe) were used. For both Asia and Europe, the pooled estimate of
Subgroup analyses by region (Asia and Europe) for pros- included studies showed no significant difference in IPSS
tate volume, PSA, IPSS, and maximal flow rate were performed between patients with and without MS (Figure 6C).
to reduce the heterogeneity among the included studies. Four Two studies from Asia24,25 reported maximal flow rate
studies from Asia22,24,25,27 reported prostate volumes for data, and there was obvious heterogeneity among studies

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 5
Wang et al Medicine  Volume 95, Number 19, May 2016

FIGURE 4. Meta-analysis for International Prostate Symptom Score (IPSS). (A) Pooled estimate. (B) Sensitivity analysis.

FIGURE 5. Meta-analysis for maximal flow rate. (A) Pooled estimate. (B) Sensitivity analysis.

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Medicine  Volume 95, Number 19, May 2016 Metabolic Syndrome and BPH

FIGURE 6. Subgroup analysis by area (Asia and Europe) (A) prostate volume (B) PSA (C) IPSS, and (D) maximal flow rate.

Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. www.md-journal.com | 7
Wang et al Medicine  Volume 95, Number 19, May 2016

(Q ¼ 130.9, P < 0.001; I2 ¼ 99.2); thus, a random-effects model presence of MS (P ¼ 0.032), but MS was not associated with the
was used. Two studies from Europe21,26 reported maximal flow severity of LUTS (P ¼ 0.144), nor was there a correlation
rate data, and minor heterogeneity was present (Q ¼ 1.9, between ED and LUTS severity (P ¼ 0.303).
P ¼ 0.163; I2 ¼ 48.5%); thus, a fixed-effects model was used. Other studies have examined the association of MS with
For both Asia and Europe, the pooled estimates showed no various measures of BPH. In a study of 401 elderly Chinese
significant difference in maximal flow rate between patients men, Zhang et al24 found that body mass index (BMI), waist
with and without MS (Figure 6D). circumference, fasting glucose, glycosylated hemoglobin, tri-
glyceride, fasting insulin, and insulin resistance assessed by
homeostasis model assessment of insulin resistance (HOMA-
DISCUSSION IR) were higher and HDL-C was lower in BPH patients with MS
This study aimed to evaluate the association of MS with than in those without MS. Furthermore, patients with MS had a
characteristics of BPH. The results showed that BPH patients significantly larger prostate volume (P ¼ 0.000) and longer
with MS had a significantly higher prostate growth rate and duration of LUTS (P ¼ 0.006), and prostate volume was posi-
larger prostate volume than those without MS. However, IPSS tively correlated with BMI (P ¼ 0.000), fasting insulin
and maximal flow rate were not different between BPH patients (P ¼ 0.001), HOMA-IR (P ¼ 0.003) and inversely correlated
with and without MS, and a borderline nonsignificant difference with HDL-C (P ¼ 0.000). In another study of 764 Chinese males
in PSA between patients with and without MS was seen. older than 40 years, multivariate analysis showed that aging,
Subgroup analysis by region, however, indicated that Asian cigarette smoking, lack of regular exercise, and larger prostate
patients with MS had a larger prostate volume and PSA than volume were independent predictors for moderate/severe
those without MS, but this finding was not present in European LUTS, and risk factors for LUTS were influenced by the
patients. Although there have been other studies examining the presence of MS.40 Ozden et al28 studied 78 patients with
association between MetS and BPH, this was the first to provide BPH and LUTS and found that those with MS had significantly
a comprehensive examination of MS and various measures higher median body weight, BMI, serum glucose, serum trigly-
of BPH. ceride, and PSA levels, but lower HDL-C level, compared with
Epidemiological studies have indicated a possible associ- BPH patients without MS. The median annual total prostate
ation between MS and prostatic conditions,30,31 and some growth rate (1.0 mL/y), and median annual transitional zone
studies have shown a increased prostate growth and larger prostate growth rate (1.25 mL/y) were significantly higher in
prostate volume in BPH patients with MS than those with- patients with MS than those without (0.64 mL/y and 0.93 mL/y,
out.4–6 It has also been reported that MS is associated with an respectively, both P < 0.05). Interestingly, a study of only
increased risk of LUTS as a result of prostatic enlargement.7,32 Chinese patients by Zou et al41 found that patients with MS
Age-related changes in androgens have been generally accepted had a significantly higher PSA level than those without MS,
to be the primary factor involved in the pathogenesis of BPH.33 which is similar to the subgroup analysis of Asian patients in our
Although it is becoming apparent that there is an associ- study. Thus, race may be a factor contributing to the different
ation with metabolic derangements and BPH, the mechanisms results in different studies.
by which the derangements of MS may led to prostatic hyper- Measures of clinical progression of BPH include quality of
plasia and LUTS remain to be fully elucidated. Some studies life, urinary retention, and risk of surgical intervention. How-
have suggested that insulin resistance and hyperinsulinemia are ever, these factors were not examined in the current analysis
possible causative factors of BPH in patients with MS.5,34–38 because of the 9 included studies, of which only 2 reported
Other authors have suggested that chronic inflammation is the results of acute urinary retention, only 2 studies reported quality
causative link between MS and LUTS and BPH. A recent of life results, and only 1 study mentioned of risk of surgical
systematic review of the literature by He et al39 suggested that intervention. Of the articles that reported rate of acute urinary
the proinflammatory state present in patients with MS results in retention, Pan et al25 found acute urinary retention in 82% of
inflammatory cell infiltration of prostatic and adipose tissue patients with MS and in 17% of patients without MS, and Cao
with subsequent tissue remodeling and overgrowth. Prostate et al27 reported a rate of 26.2% in patients with MS and 10.3% in
tissue specimens of patients with BPH have been shown to have patients without MS. Overall, the rate of acute urinary retention
elevated levels of inflammatory cells,39 and prostate volume had tendency to be higher in patients with MetS than those
and IPSS have been directly correlated with the level of without MS. As to quality of life, De Nunzio et al23 reported no
inflammation in patients with BPH/LUTS.39 difference in quality of life between patients with and without
In another recent meta-analysis, Gacci et al15 included 8 MS. Pan et al,25 however, reported that patients with MS had
studies which enrolled 5403 patients, of which 1426 had MS. significantly higher IPSS quality of life score (4.94  1.06) than
Patients with MS had a significantly higher total prostate did patients without MS (3.31  0.95) (P < 0.001).
volume as compared with those without MS (þ1.8 mL, 95% There are limitations of this analysis that have to be
CI: 0.74–2.87; P < 0.001); however, there was no difference in considered. The definition of MS used varied between the
IPSS or LUTS subdomain scores between the groups. Meta- studies, and the number of available studies and data were
regression analysis showed that differences in total prostate limited. We did not examine characteristics of MS such as BMI
volume were significantly higher in older and obese patients in and waist circumference, nor the mechanisms by which MS is
contrast to those with low HDL-C concentrations. The study did associated with BPH examined. Five studies used transrectal
not examine other measures such as prostate growth rate or ultrasonography, 1 study used transabdominal and transrectal
maximal flow. In the present study, the report by Aktas et al29 ultrasonography, 1 study used transabdominal ultrasonography,
did not include outcome measures appropriate for the meta- and 2 studies used ultrasonography without mention of the site.
analysis. The study examined the relationship between MS, Study has shown that the results from transabdominal ultra-
erectile dysfunction (ED), and LUTS in 106 patients with BPH, sonography are not consistent with those from transrectal
account off 31.1% (33) to whom had MS. The analysis showed a sonography when used to measure prostate volume,42 and this
significant difference between ED groups with respect to the may have led to bias in the measurement of prostate volume.

8 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved.
Medicine  Volume 95, Number 19, May 2016 Metabolic Syndrome and BPH

In conclusion, the results of this meta-analysis are con- in Epidemiology (MOOSE) Group. Meta-analysis of Observational
sistent with literature indicating that BPH patients with MS have Studies in Epidemiology. JAMA. 2000;283:2008–2012.
a higher prostate growth rate and larger prostate volume than 17. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale
those without MS. However, measures of LUTS were not (NOS) for assessing the quality of nonrandomised studies in meta-
different between patients with and without MS. Further study analyses. Available at: http://www.ohri.ca/programs/clinical_epide-
is necessary to elucidate the association of BPH and metabolic miology/oxford.htm.
disorder elements and the potential risk of disease progression 18. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance
in BPH patients with MS. from the median, range, and the size of a sample. BMC Medl Res
Methodol. 2005;5:13.
ACKNOWLEDGMENT 19. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic
Reviews of Interventions Version 5.1.0. The Cochrane Collaboration.
None.
2011. Available at: http://www.cochrane-handbook.org. Updated in
March 2011.
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