41 96
clinical
and pathologic
characteristics was preferred
over
a
univariable
analysis).
2.2.
Quality
of
the
selected
studies
We
assessed
the
methodological
quality
of
all
included
studies. Each
individual studywas given a summary rating of
good
(low
risk
of
bias),
fair,
or
poor
(high
risk
of
bias).
The
rating was based on
the
following components: methods
for
selecting
the participants/groups of
the study, methods used
for
randomization,
comparability,
and
assessment
of
the
outcome
or
exposure.
The
rating
for
each
study
therefore
addressed
both
study
design
and
intervention
character-
istics. All
included
studies were
rated
as
good
or
fair.
2.3.
Smoking
strata
and
clinical
end
point
definitions
For
a
reported
association of
smoking with an outcome, we
recognized
two
possible
general
stratifications
of
the
participants:
smoking
status
and
smoking
exposure.
The
following
categories
of
smoking
status
were
reported
in
included
studies: nonsmokers
or never
smokers
(a negligi-
ble number of
lifetime
cigarettes
smoked),
smokers
(a non-
negligible
number
of
lifetime
cigarettes
smoked),
former
smokers
(stopped
smoking prior
to
diagnosis),
and
current
smokers
(smoked
at
the
time
of
diagnosis).
In
studies
including
a
quitter
category,
former
smokers
stopped
smoking
1
yr
before
diagnosis,
and
quitters
stopped
smoking
between
1
yr
before
and
3 mo
after
diagnosis.
3.
Evidence
synthesis
3.1.
Association
between
erectile
dysfunction
and
smoking
3.1.1.
Epidemiological
evidence
The Massachusetts Male
Aging
Study
that
evaluated
ED
in
men
aged 40–70
yr with
a
self-administered questionnaire
first
reported
that
cigarette
smoking
at
baseline
almost
doubled
the
likelihood of moderate or
complete ED at up
to
10
yr
of
follow-up.
Former
smokers,
compared with
never
smokers, were not at
increased
risk of ED
[4], but
there was
no
information
on
dose
response
based
on
the
number
of
cigarettes
smoked.
An
earlier
study
of
Vietnam-era
veter-
ans,
aged
31–49
yr,
found
that
a
higher
percentage
of
smokers
than nonsmokers
reported ED problems. However,
neither
number
of
years
of
smoking
nor
number
of
cigarettes
smoked
per
day
were
significant
predictors
of
ED
in
current
smokers
in
this
study
[5].
In
2005
Gades
et
al
investigated
a
population-based
cohort
extrapolated
from
the
Olmsted
County
Study
of
Urinary
Symptoms and Health
Status Among Men
showing
an
association
between
smoking
and
ED.
Although
these
cross-sectional data did not prove
cause
and effect, a dose–
response
relationship was
reported. The association may be
of
greater magnitude
in
the
younger
age
group
in whom
other traditional causes of ED are not as prevalent compared
with
the
older
age
group
[3] .Another
observational
cross-sectional
study
conducted
in
Italy
showed
that
current
smokers
of
10
cigarettes per
day
(OR:
1.4;
95%
CI,
1.2–1.5;
p
<
0.0001)
and
former
smokers
(OR:
1.3;
95% CI,
1.2–1.5;
p
<
0.0001)
presented
a
higher
risk
of
developing
ED
when
compared
with
nonsmokers
[6,7].
Millett
et
al
examined
factors
associated with
ED
in
a
large
representative
sample
of
8367
Australian men
aged
16–59 yr. Compared with nonsmokers,
the adjusted ORs
for
ED
in
this
cohort were 1.24
(95% CI, 1.01–1.52;
p
= 0.04)
for
those
smoking
<
20
cigarettes
per
day
and
1.39
(95%
CI,
1.05–1.83;
p
= 0.02)
for
those
smoking
>
20
cigarettes
per
day,
after
adjusting
for
other
confounding
factors
[8].
He
et
al
examined
the
association
between
cigarette
smoking
and
risk
of
ED
among
7684
Chinese
men
aged
35–74 yr without clinical vascular disease. The OR of EDwas
1.41
(95%
CI,
1.09–1.81)
for
cigarette
smokers
compared
with
never
smokers
[9] .Chew
et
al
explored
the
relationship
between
cigarette
smoking,
ED,
and
cardiovascular
disease
(CVD)
using
data
from a population-based
cross-sectional
study of 1580 par-
ticipants.
Compared with
never
smokers,
the
odds
of
ED,
adjusted
for
age,
age
squared,
and
CVD, were
significantly
higher
among
current
smokers
(OR
2
= 1.40;
95%
CI,
1.02–1.92)
and
ever
smokers
(OR:
1.57;
95%
CI,
1.02–2.42).
Similarly,
the
adjusted
odds
of
severe
ED were
significantly higher among
former smokers. Compared with
never
smokers without
CVD,
the
age-adjusted
odds
of
ED
among
former
smokers
and
ever
smokers
without
CVD
were
about
1.6.
Interestingly,
this
study
shows
that
the
relationship
between
smoking
and
ED
is
independent
of
that
between
smoking
and
CVD
[10].
More
recently, Wu
et
al
reported
data
of
a
population-
based
study
among noninstitutionalized Chinese men
aged
17–88
yr
(Fangchenggang
Area Male
Health
Examination
Survey) where
ED was
assessed
by
using
the
international
Index
of
Erectile
Function
erectile
function
domain
score.
After
adjusting
for
age,
alcohol
drinking,
physical
activity,
hypertension, diabetes, dyslipidemia,
and obesity,
smokers
who
smoked
>
20
cigarettes
per
day
had
a
significantly
increased
risk of ED
than never
smokers
(OR
2
: 1.23; 95% CI,
1.03–1.49;
p
= 0.02). After
further adjustment
for education,
the
risk of ED was
still
significantly higher
in men
smoking
>
23
yr
than
never
smokers
(OR:
1.60;
95%
CI,
1.22–2.09;
p
= 0.001)
[11].
Table 1provides
a
detailed
overview
of
the
character-
istics, outcomes, and covariates of
studies assessing
the
risk
of
smoking
for
ED.
3.1.2.
Pathophysiologic
evidence
Considerable
evidence
supports
the
concept
that
smoking-
related
ED
is
mainly
associated
with
endothelial
im-
pairment
and
reduction
in
nitric
oxide
(NO)
availability.
Smoking
provokes
different
detrimental
effects
on
the
endothelial
cells,
based
on
architectural
and
functional
changes
that
include
decreased
endothelial
nitric
oxide
synthase
(eNOS) activity,
impaired endothelium-dependent
vasorelaxation,
increased
expression
of
cell
adhesion
molecules
and
transendothelial
migration
of
monocyte-
like
cells,
reduced
response
to
vascular
endothelial
growth
factor,
and
impaired
regulation
of
important
thrombotic
E U R O P E A N
U R O L O G Y
F O C U S
1
( 2 0 1 5
)
3 9 – 4 6
41