Risk Factors for Progression or Improvement of Lower

Urinary Tract Symptoms in a Prospective Cohort of Men

Sean Martin, Kylie Lange, Matthew T. Haren, Anne W. Taylor, Gary Wittert*
and Members of the Florey Adelaide Male Ageing Study
From the Freemasons Foundation Centre for Mens Health (SM, MTH, GW), School of Medicine (SM, KL, GW),
and Population Research and Outcome Studies (MTH), University of Adelaide, and SANSOM Institute,
Division of Health Sciences, University of South Australia (AWT), Adelaide, South Australia
Purpose: We determined the metabolic, lifestyle and physical factors associated
with progression or improvement of storage and voiding lower urinary tract
symptoms in a population based cohort of men.
Materials and Methods: After the exclusion of men with prostate or bladder
cancer and/or surgery from the study, progression and improvement of storage
and voiding lower urinary tract symptoms was assessed using the AUA-SI
(American Urological Association symptom index) in 780 men, age 35 to
80 years at baseline, who attended 5-year followup clinics.
Results: Storage and voiding lower urinary tract symptoms progressed in 39.8%
(308) and 32.3% (250) of men, and improved in 33.1% (256) and 23.4% (181),
respectively. In nal adjusted regression models greater bother and physical
activity at baseline predicted improvement in storage and voiding lower urinary
tract symptoms, while greater income, high-density lipoprotein cholesterol and
lower triglycerides predicted improvement of storage lower urinary tract symp-
toms only. Being widowed, higher plasma estradiol and depression at baseline
predicted the progression of storage and voiding lower urinary tract symptoms,
while greater abdominal fat mass and obstructive sleep apnea risk predicted the
progression of storage lower urinary tract symptoms only. Older age, lower high-
density lipoprotein cholesterol, testosterone, income, previous benign prostatic
hyperplasia and erectile dysfunction at baseline predicted the progression of
voiding lower urinary tract symptoms only. The initiation or continued use of
a-blockers or anticholinergics (storage lower urinary tract symptoms), and
5a-reductase inhibitors (voiding lower urinary tract symptoms), were associated
with symptom improvement.
Conclusions: Lower urinary tract symptoms may progress or remit. Even
accounting for medication use, progression may be associated with modiable
disease, or metabolic or behavioral factors, which are also risk factors for type 2
diabetes and cardiovascular disease. These factors should be looked for and
managed.
Key Words: prostatism, epidemiology, urinary tract physiological
phenomena, cohort studies, mens health
ALTHOUGH common and associated
with reduced quality of life and
increased health care expenditure,
1
there are only limited data relating
to the outcome of lower urinary tract
symptoms in men over time.
25
While
Abbreviations
and Acronyms
BPH benign prostatic
hyperplasia
CV coefficient of variance
HDL high-density lipoprotein
LUTS lower urinary tract
symptoms
OSA obstructive sleep apnea
Accepted for publication June 4, 2013.
Study received Research Ethics Committee
approval.
Supported by the Australian National Health
and Medical Research Council (Project Grant
#627227).
* Correspondence: Freemasons Foundation
Centre for Mens Health, University of Adelaide,
Lv. 6, Eleanor Harrald Bldg, Frome Rd., Adelaide,
S.A., 5000, South Australia, Australia (telephone:
61 [8] 8222 5502; FAX: 61 [8] 8223 3870; e-mail:
gary.wittert@adelaide.edu.au).
See Editorial on page 15.
130 j www.jurology.com
0022-5347/14/1911-0130/0
THE JOURNAL OF UROLOGY

2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.

http://dx.doi.org/10.1016/j.juro.2013.06.018
Vol. 191, 130-137, January 2014
Printed in U.S.A.
usually assumed to worsen, LUTS may also
improve.
3,6
A number of risk factors and health
conditions other than age and BPH associate with
LUTS in men,
7
suggesting that the lower urinary
tract is susceptible to systemic inuences outside of
the prostate. Furthermore, these associations vary
according to specic clusters of urinary symptoms.
8
In a study of elderly men from the MrOS
(Osteoporotic Fractures in Men) Study with clini-
cally signicant LUTS at baseline, more than a
quarter reported signicant symptom improvement
at followup.
3
In an earlier study of Swedish men 45
to 99 years old, 20.2% and 9.5% had remitting uri-
nary incontinence and overactive bladder, respec-
tively, although only an overall symptom score was
obtained.
4
Few studies have simultaneously exam-
ined the contribution of multiple risk factors to the
progression or improvement of specic symptom
clusters in men.
In this study we determined the prevalence,
incidence and improvements of storage and voiding
LUTS in a population based cohort of men with
detailed psychosocial, health related and behavioral
assessments during 5 years. We tested the hypoth-
esis that the onset and course of LUTS are deter-
mined, at least in part, by potentially remediable
factors.
METHODS
Study Design and Sampling
Data were obtained from the FAMAS (Florey Adelaide
Male Ageing Study), a population based study of
randomly selected men from the northern and western
suburbs of Adelaide, Australia.
9
A total of 1,620 men 35 to
80 years old at recruitment completed a telephone inter-
view (sample response rate 67.8%) and 1,195 attended
a clinic visit (T1, clinic response rate 45.1%) between
2002 and 2005. Written, informed consent was obtained
from all participants. All protocols were approved by the
Royal Adelaide Hospital Research Ethics Committee,
with funding currently provided through the Australian
National Health and Medical Research Council (Project
Grant #627227).
Comparisons to the 2001 Australian Census data
showed that FAMAS participants matched the population
for most key demographics, although younger groups and
never married men were underrepresented and older
participants were overrepresented.
9
Followup clinic visits
using identical protocols were conducted between 2007 and
2010 (T2, 899), as near was practical to 5 years after the
initial visit (mean followup 5.0 0.2 years). Comparison to
the 2006 Australian Census data showed that FAMAS
participants were more likely to be older, married and have
a higher level of post-secondary school education.
10
Lower Urinary Tract Symptoms
The 7-item AUA-SI was used to evaluate the presence
of LUTS. Subjects were classied as having storage
symptoms if the sum of the score on AUA-SI items 2, 4
and 7 was 4 or greater (and the score on item 4, urgency,
was 1 or greater), and as having voiding symptoms if the
sum of the score on AUA-SI items 1, 3, 5 and 6 was 5 or
greater. Subjects were classied as having mild, moderate
or severe LUTS if the total LUTS score was 0 to 7, 8 to 19,
or 20 to 35, respectively. Given the absence of standard-
ized denitions for LUTS progression and improvement,
we dened these outcomes based on previous studies
3
and
AUA management guidelines.
11
Men who reported an
increase in AUA-SI score for voiding symptoms of 3 or
more and for storage symptoms 2 or more were classied
as having voiding and storage LUTS progression,
respectively. Men who reported a decrease in AUA-SI
score for voiding symptoms of 3 or less and for storage
symptoms 2 or less were classied as having voiding and
storage LUTS improvement, respectively (with a 2 to 2
and 1 to 1-point absolute changes in voiding and storage
symptoms classied as stable).
Demographic Factors, Health Status and
Medication Use
Information on age, education, and marital, occupational,
smoking and disease status was obtained by self-report
questionnaire.
9
Medication use was determined by self-
report and data linkage with a national medication
registry. The presence of depression was assessed using
the Beck Depression Inventory (BDI-1A
12
) or a report of
physician diagnosed depression and/or use of antidepres-
sant medication. The probability of obstructive sleep
apnea was determined using a multivariate prediction
equation.
13
Plasma Assays
Morning fasting venous blood samples were obtained by
venipuncture at clinic and stored at 80C. Serum total
testosterone was measured by validated stable isotope
dilution liquid chromatography-tandem mass spectrom-
etry (interassay CV 9.3% at 0.43 nmol/l, 8.6% at
1.66 nmol/l, 4.0% at 8.17 nmol/l) as was estradiol (E
2
)
(interassay CV 14% at 23 pmol/l, 4.0% at 83 pmol/l, 6.0%
at 408 pmol/l). HDL, low-density lipoprotein cholesterol
and triglycerides were measured enzymatically using a
Hitachi 911 (Boehringer Ingelheim, Ingelheim, Germany;
interassay CV triglyceride 3%, total cholesterol 2.3%,
HDL 6.7% and low-density lipoprotein 3.7%). Plasma
glucose was determined using an automated chemistry
analyzer system (Olympus AU5400, interassay CV 2.5%
at 3.5 mmol/l and 3.0% at 19.6 mmol/l). Glycated hemo-
globin (HbA1c) was measured by high-pressure liquid
chromatography using a spherical cation exchange gel
(CV 2% at 6% of total hemoglobin).
Body Composition
Anthropometric measures, blood pressure, grip strength
and body composition (by dual energy x-ray absorptiom-
etry) were obtained as previously published.
9
Statistical Analysis
In the present study only men who had completed the
AUA-SI at T1 and T2 (822) were included in the study.
Men with a history of bladder cancer (8) or prostate cancer
(17) or prostate surgery (12) and those with a current
RISK FACTORS FOR PROGRESSION OR IMPROVEMENT OF LOWER URINARY TRACT SYMPTOMS 131
self-reported urinary tract infection (5), were excluded
from the analysis. In total, 780 men were included in the
nal analytic sample (g. 1). There were no signicant
demographic differences between men at T1 and T2. For
the multinomial logistic regression models, independents
were rst selected on the basis of demonstrated or sus-
pected associations with the outcome. Those predictors
with a univariate association with the outcome variable of
p 0.1 were then adjusted for age and included in the
nal regression model only if they demonstrated an age
adjusted association with p 0.1. To determine the effect of
selected medication classes (a-blockers, anticholinergics,
diuretics, 5a-reductase inhibitors) on the nal model, a
sensitivity analysis was performed using sequential
logistic regression to test for signicant changes to the
observed regression coefcients for men taking selected
medications at baseline only (model 1) or at followup
(model 2). All data were analyzed using PASW Statis-
tics 19.0.
RESULTS
Study Population
The supplementary table (http://jurology.com/)
details the characteristics of participants at each
point. At followup the mean total AUA-SI score was
approximately 0.5 points higher, and the degree of
bother for storage or voiding LUTS did not change,
but mean plasma prostate specic antigen concen-
tration increased.
LUTS Prevalence
Between baseline and followup visits the proportion
of men who reported mild LUTS decreased from
81.9% to 74.5% while the proportion who reported
moderate (15.6% to 22.7%) and severe symptoms
(2.5% to 5.3%) increased (table 1). Increases in
moderate symptoms occurred in all but the oldest
age group, where it was the severe symptoms that
increased.
The proportion of men reporting signicant
storage (AUA-SI score 4 or greater) and voiding
(AUA-SI score 5 or greater) LUTS increased to
34.6% (from 27.5%) and 17.7% (from 13.1%),
respectively. There was an age related increase in
both types of LUTS with time.
LUTS Improvement and Progression
Storage LUTS remained stable (1 to 1-point ab-
solute change in storage symptom AUA-SI score)
between visits in 27% (209), improved (change in
AUA-SI score of 2 or less) in 33.1% (256) and pro-
gressed (change in AUA-SI score of 2 or more) in
39.8% (308) of men. Voiding symptoms remained
stable (2 to 2-point absolute change in voiding
symptom AUA-SI score) in 44.0% (344), improved
(change in AUA-SI score of 3 or less) in 23.4% (181)
and progressed (change in AUA-SI score of 3 or
more) in 32.3% (250) of men (g. 2).
The baseline predictors of change in storage and
voiding LUTS from the multi-adjusted models are
shown in gures 3 and 4. Being widowed, sedentary,
having lower plasma HDL cholesterol and higher
estradiol, OSA risk and the use of a-blockers at
baseline increased the likelihood of storage symp-
tom improvement and decreased that of progres-
sion. Greater urinary bother, lower triglycerides,
greater sexual desire and use of anticholinergics
were associated with improvement in symptoms.
Greater abdominal fat mass, lower income and a
diagnosis of depression were associated with pro-
gression of storage LUTS (g. 3). Older age, urinary
bother, being widowed, being sedentary, lower
Figure 1. CONSORT (Consolidated Standards of Reporting
Trials) diagram of analytic sample of cohort of Australian men.
Table 1. Prevalence of total, storage and voiding LUTS
Age Group
% Mild
LUTS (No.)
% Moderate
LUTS (No.)
% Severe
LUTS (No.)
% Storage
LUTS (No.)
% Voiding
LUTS (No.)
Baseline:
35e39 86.3 (69) 12.5 (10) 1.3 (1) 22.5 (18) 6.3 (5)
40e49 87.4 (216) 10.9 (27) 1.5 (4) 22.7 (56) 8.9 (22)
50e59 87.7 (229) 10.7 (28) 1.5 (4) 23.7 (62) 9.2 (24)
60e69 75.6 (99) 21.4 (28) 3.1 (4) 29.0 (38) 20.5 (27)
70e80 72.4 (42) 22.4 (13) 5.2 (3) 39.7 (23) 20.7 (12)
81e85
Overall 81.9 (655) 15.6 (106) 2.5 (16) 27.5 (197) 13.1 (90)
Followup:
35e39
40e49 81.3 (65) 18.8 (15) 0.5 (1) 31.6 (25) 11.3 (9)
50e59 85.8 (212) 13.0 (32) 2.3 (5) 21.5 (53) 11.4 (28)
60e69 79.1 (208) 18.6 (49) 4.8 (6) 33.0 (86) 16.1 (42)
70e80 71.2 (94) 23.5 (31) 7.3 (11) 43.5 (57) 16.8 (22)
81e85 55.2 (32) 39.7 (23) 9.2 (14) 43.1 (25) 32.8 (19)
Overall 74.5 (611) 22.7 (150) 5.3 (37) 34.6 (246) 17.7 (120)
Participants with missing values were not included in the study (16, 12, 8, 14 and
10 for mild, moderate, severe, storage and voiding LUTS at baseline, and 13, 8, 3,
11 and 7 for mild, moderate, severe storage and voiding LUTS at followup,
respectively).
132 RISK FACTORS FOR PROGRESSION OR IMPROVEMENT OF LOWER URINARY TRACT SYMPTOMS
plasma testosterone, a diagnosis of BPH and using
5a-reductase inhibitors were associated with a
greater likelihood of improvement and a lower
likelihood of progression of voiding symptoms. Lower
household income, lower plasma HDL cholesterol,
higher estradiol, a diagnosis of depression and
Figure 2. Change in voiding and storage LUTS in cohort of Australian men during baseline (2002 to 2005) and followup (2007 to 2010)
clinic visits. Progression was dened as new reports of signicant symptoms from T1 to T2 for storage (4 or more) and voiding (5 or
more) LUTS, and LUTS remission was dened as disappearance of signicant symptoms from T1 to T2.
Figure 3. Final multi-adjustedmodels for progressionor improvement of storage LUTSincludingrange of social, lifestyle andbiomedical
variables. Data represent ORs with 95% CIs. Independent variables with univariate association with dependent of p 0.1 were included
in nal models if age adjusted association had p 0.1. Listed ORs represent likelihood of symptom improvement (blue bars) or
progression (red bars) at 5-year clinic for storage LUTS for each variable listed (referent category stable LUTS). For each categorical
factor, referent category appears on OR 1 line. OR to left of line indicates less likely to occur whereas OR to right indicates more
likely. For each continuous variable ORs represent change in likelihood of symptom improvement or progression per SD increase.
Some variables were predictors of improvement and regression. Abdo. FM, abdominal fat mass. Sep./Div., separated/divorced. IPSS,
International Prostate Symptom Score. DEXA, dual energy x-ray absorptiometry. NPAS, National Physical Activity Society.
RISK FACTORS FOR PROGRESSION OR IMPROVEMENT OF LOWER URINARY TRACT SYMPTOMS 133
erectile dysfunction at baseline were associated with
the progression of voiding symptoms (g. 4).
Effect of Pharmacotherapy on LUTS
Tables 2 and 3 show the relationships between the
use of medications for LUTS at baseline and
followup, and changes in LUTS. Storage LUTS were
more likely to improve and less likely to progress in
men who continued to take or were commenced on
a-blockers and anticholinergics at followup (table 2).
Voiding LUTS were more likely to improve in men
who had commenced 5a-reductase inhibitors at
followup, and were less likely to progress in those
who continued to take or commenced 5a-reductase
inhibitors (table 3).
DISCUSSION
Overall we observed an age dependent increase in
the severity of LUTS during the 5-year followup
consistent with previous studies.
24,6
In the
Olmsted County Study of similar age men the mean
AUA-SI increased at 42 months, but notably some
men experienced improvement.
5
In a subsequent
analysis of Olmsted County men combined with
men from the Flint Mens Health Study,
14
49.2%
and 38.2% of men had increasing and decreasing
symptom severity, respectively, but storage and
voiding symptoms were not examined separately.
In a multicenter Scottish survey of men age 40 to
79 years,
15
improvement in storage and voiding
symptoms occurred in half as many men compared
to the current study. This nding is likely due to the
exclusion from the baseline sample of a center with
higher symptom scores (due to methodological dif-
ferences). The observation that men with greater
urinary bother at baseline were more likely to
report voiding dysfunction at followup is consistent
with the ndings of previous studies.
1
In cross-sectional studies physical activity has
been shown to be protective against the develop-
ment of LUTS,
16
and recent longitudinal data from
the MrOS cohort have conrmed the protective
effect of physical activity on LUTS.
17
We have
further shown that a high level of physical activity
predicts the improvement and protects from the
progression of storage and voiding LUTS.
Widowhood was associated with a greater likeli-
hood of progression, and decreased the likelihood of
improvement of storage and voiding LUTS. This
nding adds to the range of conditions associated
with widowhood, including erectile dysfunction,
Figure 4. Final multi-adjusted models for progression or improvement of voiding LUTS including range of social, lifestyle and
biomedical variables. Data represent ORs with 95% CIs. Independent variables with univariate association with dependent of p 0.1
were included in nal models if age adjusted association had p 0.1. Listed ORs represent likelihood of symptom improvement
(blue bars) or progression (red bars) at 5-year clinic for voiding LUTS for each variable listed (referent category stable LUTS). For
each categorical factor, referent category appears on OR 1 line. OR to left of line indicates less likely to occur whereas OR to
right indicates more likely. For each continuous variable ORs represent change in likelihood of symptom improvement or
progression per SD increase. Some variables were predictors of improvement and regression. Sep./Div., separated/divorced. IPSS,
International Prostate Symptom Score. NPAS, National Physical Activity Society.
134 RISK FACTORS FOR PROGRESSION OR IMPROVEMENT OF LOWER URINARY TRACT SYMPTOMS
diabetes and depression.
18
Accordingly, particular
vigilance is required in assessing and treating men
who have lost a spouse.
Data from cross-sectional
19
and longitudinal
20
studies demonstrate an association between depres-
sion and LUTS in men. Similarly we found that
depression is associated with an increased risk of
LUTS progression, an effect independent of other
lifestyle and medical factors. Furthermore, we
showed that the presence of depression at baseline
(dened with self-report, BDI score and/or antide-
pressant use) preceded the progression of storage
and voiding symptoms.
Although low HDL cholesterol is an established
risk factor for BPH,
16
our study remains the rst
to our knowledge to demonstrate an association
between lower HDL cholesterol and the cluster of
voiding-type symptoms. Similarly, while there has
been some limited evidence suggesting a link
between triglycerides and, specically, overactive
bladder in clinical samples,
21
our nding of a
decreased likelihood of storage LUTS improvement
in men with high triglycerides at baseline is
consistent with the notion that storage LUTS may
be a component of the metabolic syndrome.
8
Sleep disorders have recently been recognized as
a potential risk factor for LUTS.
22
Our previous
analyses
8
and those of others
23
have suggested an
independent relationship between OSA and LUTS.
We found that higher OSA risk at baseline was
associated with an increased likelihood of storage
LUTS progression at followup. This observation is
consistent with the relationship between OSA and
the metabolic syndrome, with signicant improve-
ment in AUA-SI after continuous positive airway
pressure therapy for 3 months in older men.
24
Table 2. Effect of LUTS medications at baseline and followup on storage LUTS changes (AUA-SI)
LUTS Medications Multivariate Storage LUTS Improvement* Multivariate Storage LUTS Progression*
% (No.) OR
95% CI
p Value R
2
Change OR
95% CI
p Value R
2
Change Lower Upper Lower Upper
a-Blockers:
Baseline 9.7 (75) 1.82 1.59 2.22 0.003 0.44 0.28 0.79 0.039
/ 5.0 (39) 1.94 0.89 3.07 0.191 0.08 0.31 0.16 1.23 0.341 0.16
/ 4.7 (36) 1.71 1.38 2.26 0.041 0.13 0.59 0.20 1.09 0.061 0.20
/ 3.5 (27) 2.11 1.42 3.01 0.012 0.16 0.49 0.18 0.79 0.038 0.11
/ 86.8 (672) Ref Ref
Anticholinergics:
Baseline 5.1 (39) 2.69 1.99 3.74 0.038
/ 1.6 (12) 3.22 0.81 5.72 0.527 0.10
/ 3.5 (27) 2.11 1.32 4.01 0.038 0.20
/ 7.0 (54) 3.42 1.65 5.21 0.009 0.22
/ 87.9 (678) Ref
Data presented are OR (95% CI) from binomial regression of storage LUTS improvement and progression (referent category stable storage LUTS). Medication classes were
selected on the basis of an independent effect on storage LUTS improvement or progression (fig. 3), and listed as baseline predictors and by changes at followup.
Medication use assessed through Pharmaceutical Benefits Scheme linkage and/or self-report.
*Regression models were also controlled for bother with urinary symptoms, abdominal fat mass, household income, marital status, physical activity, serum HDL, triglyceride
and estradiol, depression and solitary sexual desire.
Model fit was assessed through use of pseudo R
2
(Nagelkerke). R
2
change refers to the overall fit for the final models, and was storage LUTS improvement (0.34) and
progression (0.55).
Table 3. Effect of LUTS medication at baseline and followup on voiding LUTS changes (AUA-SI)
% (No.)
Multivariate Voiding LUTS Improvement* Multivariate Voiding LUTS Progression*
OR
95% CI
p Value R
2
Change OR
95% CI
p Value R
2
Change Lower Upper Lower Upper
5a-Reductase inhibitor:
Baseline 5.5 (43) 4.01 3.11 4.89 0.003 0.62 0.39 0.79 0.009
/ 3.5 (27) 2.67 0.89 5.11 0.382 0.17 0.72 0.11 1.31 0.341 0.11
/ 2.0 (15) 2.11 0.09 4.18 0.071 0.07 0.51 0.31 0.88 0.008 0.08
/ 3.0 (23) 3.12 0.89 6.01 0.042 0.18 0.58 0.19 0.79 0.028 0.21
/ 91.5 (704) Ref Ref
Data presented are OR (95% CI) from binomial regression of voiding LUTS improvement and progression (referent category stable voiding LUTS). Medication classes were
selected on the basis of an independent effect on voiding LUTS improvement or progression (fig. 3), and listed as baseline predictors and by changes at followup. Medication
use was assessed through Pharmaceutical Benefits Scheme linkage and/or self-report.
*Regression models were also controlled for age category, bother with urinary symptoms, household income, marital status, physical activity, serum HDL, testosterone and
estradiol, depression, benign prostatic hyperplasia and erectile dysfunction.
Model fit was assessed through use of pseudo R
2
(Nagelkerke). The overall fit for the final models was voiding LUTS improvement (0.43) and progression (0.56).
RISK FACTORS FOR PROGRESSION OR IMPROVEMENT OF LOWER URINARY TRACT SYMPTOMS 135
Previous studies examining the effect of testos-
terone on LUTS have produced positive,
25
nega-
tive
26
or equivocal
27
associations. In multivariate
models lower plasma testosterone increased the
likelihood of voiding LUTS progression, indepen-
dent of BPH, arguing against a direct effect of
androgens on the pathogenesis of BPH. Higher
plasma estradiol was associated with an increase in
storage and voiding symptoms, an effect consistent
with the emerging role of estradiol in the lower
urinary tract of men.
28
The sensitivity analyses show the benet of
ongoing use or introduction of a-blockers or anti-
cholinergics for storage LUTS in accordance with
contemporary urological practice.
11
Similarly the
improvement in symptoms of voiding LUTS,
the introduction of 5a-reductase inhibitors and
the decrease in progression with continued use are
consistent with the established effect of these
medications.
12
In accordance with the hypothesis we have iden-
tied that potentially remediable factors beyond the
prostate signicantly affect the progression or
remission of LUTS. High levels of physical activity
favorably inuenced the outcome of storage and
voiding LUTS. In the case of storage LUTS,
improvement occurred in men with higher HDL
cholesterol and lower triglycerides and OSA risk. In
contrast, greater abdominal fat mass and depression
increased the risk of storage LUTS progression. The
progression of voiding LUTS was predicted by lower
serum testosterone, higher estradiol, depression,
BPH and erectile dysfunction. The identication of
these modiable systemic factors is signicant
because of the previous demonstration of improve-
ment in LUTS with diet induced weight loss,
29
treatment of OSA by continuous positive airway
pressure
24
and increased physical activity.
30
The strengths of this study include the use of a
comparatively large, random sample of men from a
broad age group, similar in characteristics to men
from the general Australian population,
9
a com-
prehensive biopsychosocial data set (including the
use of a state-of-the-art mass spectrometer to analyze
sex hormones), and the use of conservative estimates
of remitting, stable and progressing urinary symp-
toms for storage and voiding LUTS. The limitations
of this study include the availability of 2 time points
only, and the reliance on self-reported measures
for most chronic conditions and demographic data.
CONCLUSIONS
Given the high prevalence and burden of LUTS
among men age 40 or older, attention should be paid
to addressing remediable factors instead of or as
an adjunct to specic pharmacotherapy or surgery,
not only because of the benet for the symptoms
but also because of the potential to reduce overall
cardiometabolic risk.
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