Genitourin
Med
1996;72:330-333
Is
oral
contraceptive
associated
with
genital
warts?
J
D
C
Ross
Objective:
To
measure
the
association
between
oral
contraceptive
use
and
the
prevalence
of
genital
warts
in
women.
Methods:
Cross
sectional
case
control
study
comparing
oral
contraceptive
use
in
women
with
and
without
genital
warts
attending
a
city
centre
genitourinary
medicine
clinic
controlling
for
recent
sexual
activity,
the
presence
of
other
sexually
transmitted
infections,
socio-economic
class
and
history
of
pregnancy
using
a
multivariate
logistic
regression
model.
Results:
After
controlling
for
potential
confounding
variables
women
with
genital
warts
were
sig-
nificantly
more
likely
to
be
current
users
of
the
oral
contraceptive
pill
(OR
1.7,
95%
CI
1.3-2-2).
Conclusion:
The
study
suggests
that
women
taking
the
oral
contraceptive
may
be
at
increased
risk
of
presenting
with
genital
warts.
Previously
published
papers
provide
some
support
for
this
hypothesis
and
potential
biological
mechanisms
are
discussed.
(Genitourin
Med
1996;72:330-333)
Keywords:
oral
contraceptive
pill;
genital
warts;
human
papillomavirus;
STD;
genitourinary
medicine
Introduction
Genital
warts
are
one
of
the
commonest
con-
ditions
diagnosed
and
treated
in
genitourinary
medicine
clinics
and
the
prevalence
of
human
papillomavirus
(HPV)
infection
continues
to
increase
in
contrast
to
the
decline
in
many
bacterial
sexually
transmitted
infections
in
the
UK.'
The
association
between
certain
sub-
types
of
HPV
and
genital
neoplasms,
particu-
larly
cervical
carcinoma,
is
a
source
of
considerable
confusion
and
worry
to
many
patients
particularly
since
current
treatment
options
have
limited
value
in
clearing
HPV
from
affected
skin
and
are
largely
confined
to
cosmetic
improvement.
Preventive
measures,
such
as
the
use
of
barrier
contraception,
are
also
of
limited
efficacy
since
HPV
infection
is
often
present
in
adjacent
apparently
normal
skin
and
asymptomatic
viral
carriage
is
likely.2
Thus
at
present
there
is
a
rising
prevalence
of
genital
warts,
with
lack
of
an
effective
cure,
concerns
about
the
long-term
consequences
of
infection
and
often
frequent
recurrences
despite
therapy.
In
addition,
the
clinical
impression
of
a
heterogeneous
response
of
patients
to
treatment
suggests
that
other
inde-
pendent
factors
may
influence
the
severity
and
duration
of
infection
with
a
small
subgroup
of
patients
having
a
prolonged
and
recurrent
course
of
infection
despite
therapy.
A
number
of
studies
have
suggested
that
use
of
the
combined
oral
contraceptive
pill
(OCP),
particularly
after
prolonged
exposure,
is
asso-
ciated
with
an
increased
risk
of
cervical
dyspla-
sia
and
cervical
carcinoma.3
-6
If
certain
HPV
types
increase
the
risk
of
cervical
dysplasia7
is
it
possible
that
steroid
hormones
in
the
OCP
increase
the
acquisition
and/or
expression
of
HPV
leading
to
cervical
dysplasia?
Support
for
this
hypothesis
is
provided
by
studies
suggest-
ing
that
increasing
oestrogen
levels
are
associ-
ated
with
reduced
cell
mediated
immunity"9
and
that
the
transforming
ability
of
certain
HPV
types
may
be
enhanced by
gluco-
corticoids.
'0
This
cross
sectional
case
control
study
assessed
whether
there
was
an
association
between
oral
contraceptives
and
the
presence
of
genital
warts
by
comparing
the
prevalence
of
OCP
use
in
women
with
and
without
genital
warts
attending
a
genitourinary
medicine
clinic
whilst
controlling
for
potential
con-
founding
variables.
Methods
All
women
who
presented
with
a
diagnosis
of
first
episode
genital
warts
between
the
January
and
31
December
1994
at
the
Department
of
Genitourinary
Medicine,
Edinburgh
Royal
Infirmary
over
the
age
of
15
years
and
not
known
to
be
HIV
positive
were
allocated
to
the
study
group.
The
control
group
was
com-
prised
of
a
randomly
selected
group
of
women
who
attended
over
the
same
time
period
and
who
were
also
over
the
age
of
15,
not
known
to
be
HIV
positive,
not
attending
solely
for
an
HIV
antibody
test
(unless
also
screened
for
sexually
transmitted
diseases
[STDs])
and
not
known
to
have
a
past
history
of
genital
warts.
Information
was
collected
from
the
patients'
casenotes
on
age,
the
presence
of
specific
infections
likely
to
have
been
acquired
sexually
(gonorrhoea,
chlamydia,
syphilis,
pubic
lice
and
first
episode
genital
herpes),
a
past
history
of
pregnancy,
the
number
of
sex-
ual
partners
within
the
past
3
months,
the
socio-economic
class
of
the
patient
(based
on
occupation)
and
whether
the
patient
was
cur-
rently
taking
oral
contraceptives.
This
infor-
mation
was
routinely
recorded
on
a
proforma
within
the
notes
of
each
patient
at
the
first
visit.
An
initial
power
analysis
showed
that
842
patients
would
be
required
to
have
an
80%
chance
of
detecting
a
1.5
fold
difference
in
the
use
of
oral
contraceptive
between
patients
with
and
without
warts,
with
95%
confidence.
A
multivariate
logistic
regression
model
was
used
to
compare
the
use
of
oral
contraceptives
in
patients
with
and
without
genital
warts
con-
trolling
for
sexual
activity,
age,
presence
of
Clinical
Paper
Department
of
Genitourinary
Medicine,
Edinburgh
Royal
Infirmary,
Edinburgh
EH3
9YW,
UK
J
D
C
Ross
Address
correspondence
to:
Dr
J
D
C
Ross,
Department
of
GU
Medicine,
Royal
Infirmary
of
Edinburgh,
Edinburgh
EH3
9YW,
UK.
Accepted
for
publication
9
July
1996
330
Is
oral
contraceptive
associated
with
genital
warts?
LZ
Patients
with
Warts
(n
=
429)
ME
Control
Group
(n
=
418)
Gonorrhoea
0
10
20
30
Distribution
of
STDs
in
patients
with
warts
and
in
control
groups.
other
sexually
transmitted
di
economic
class
and
past
history
(
The
data
were
entered
onto
ti
base
package
(Borland)
and
expi
sis
carried
out
using
the
Epi
(WHO
Public
Domain).
Logis
analysis
was
performed
using
the
cal
package
(SPSS
Inc.).
Results
Over
the
one
year
study
period
patients
attended
with
a
total
of
tic
episodes.
Four
hundred
anc
women
had
a
first
episode
of
ger
were
allocated
to
the
study
groul
the
remaining
women
were
as
control
group.
The
presence
of
group
is
shown
in
the
figure.
more
patients
in
the
control
groL
nosis
of
first
episode
genital
herp
109,
95%
CI
3-9-42
4).
On
initial
univariate
compo
cantly
more
women
with
genit
Multivariate
analysis
comparing
oral
contraceptive
use
in
patients
with
ai
warts
Variable
Age
group
(years):
16-20
21-25
26-30
31-35
over
35
STD:
yes
no
Socio-economic
class:
1-2
3-5
unknown
History
of
pregnancy:
yes
no
unknown
Partners
within
past
3
months:
none
1
more
than
1
unknown
Current
OCP
use:
yes
no
unknown
Patients
without
warts
63
129
111
46
69
91
327
38
190
190
182
189
47
20
334
24
40
153
184
81
Patients
with
warts
134
154
73
25
43
38
391
30
193
206
136
258
35
55
316
28
30
204
196
29
50
40
seases,
socio-
of
pregnancy.
le
dBase
data-
current
users
of
the
oral
contraceptive
pill
(204/429
[48%])
compared
with
the
control
women
who
had
no
clinical
evidence
of
HPV
infection
(153/418
[37%])
(odds
ratio
1-6,
95%
CI
1.2-2.1).
The
results
of
multivariate
analysis
controlling
for
the
other
measured
variables
are
shown
in
the
table.
Genital
warts
were
more
common
in
patients
aged
between
21-25
years
compared
with
older
or
younger
age
groups.
Individuals
with
warts
were
also
less
likely
to
admit
to
having
a
sexual
partner
within
the
previous
3
months
and
were
half
as
likely
to
have
a
concurrent
STD.
Current
OCP
use
remained
significantly
associated
with
a
clinical
presentation
with
genital
warts
after
multivariate
analysis.
Owing
to
the
larger
number
of
patients
with
herpes
in
the
control
group
the
analysis
was
repeated
controlling
for
herpes
as
a
separate
variable.
OCP
use
remained
a
significantly
associated
with
genital
warts
(odds
ratio
1-7,
95%
CI
1-3-2.1).
[oratory
analy-
Discussion
iInfo
package
In
women
attending
a
city
centre
genitouri-
;tic
regression
nary
medicine
clinic
who
presented
with
clini-
SPSS
statisti-
cally
apparent
genital
warts
a
significantly
larger
proportion
were
taking
the
oral
contra-
ceptive
pill
after
controlling
for
recent
sexual
activity,
age,
the
presence
of
other
STDs,
socio-economic
class
and
history
of
pregnancy
l
2489
female
(OR
1.7,
95%
CI
1.3-2.2).
Thus
if
there
were
2785
diagnos-
a
causal
relationship
between
the
OCP
and
A
twenty
nine
genital
warts
the
proportion
of
warts
attribut-
iital
warts
and
able
to
the
OCP
would
be
41%
(attributable
p
while
418
of
risk
%
=
relative
risk
-
1/relative
risk
x
100).
signed
to
the
Women
with
warts
were
more
likely
to
be
aged
STDs
in
each
in
their
early
20s
and
were
less
likely
to
have
Significantly
had
a
recent
sexual
partner
or
concurrent
ap
had
a
diag-
STD
than
the
control
group.
)es
(odds
ratio
There
are
various
mechanisms
by
which
oestrogen
and
progesterone
may
affect
the
arison
signifi-
immune
system
and
increase
susceptibility
to
al
warts
were
viral
infection.
Glucocorticoid
hormones
may
enhance
the
transcription
of
HPV
in
vivo
and
in
vitro
"
12
and
women
on
the
OCP
may
have
a
nd
without
genital
higher
prevalence
of
HPV.
'3
Immunity
to
viral
infection
may
also
be
reduced
by
elevated
OR
(95%
CI)
oestrogen
levels
inhibiting
natural
killer
cell
activity.8
Cellular
immunity,
as
assessed
by
1
phytohaemagluttinin
induced
lymphocyte
017
(015-.97)*
transformation,
is
reduced
in
OCP
users
and
0-6
(0-4-0-99)*
this
effect
is
independent
of
the
length
of
0-7
(0-5-0-97)*
exposure
to
OCP
or
the
brand
of
OCP.9
The
0
5
(0.4-0.6)*
latter
study
suggested
that
OCP
use
had
little
1
effect
on
the
humeral
immune
system
1
(07-1
.5)*
although
there
is
some
evidence
that
oestro-
1(07-1-2)
gens
may
stimulate
humeral
immunity
and
antibody
production
via
the
inhibition
of
sup-
0-9
(0-7-1-4)
pressor
T
cells.'4
0-8
(04-1-6)
Three
recent
studies
have
used
polymerase
chain
reaction
to
detect
HPV
in
the
genital
2-5
(1.54.2)*
tract
of
women
in
high
and
low
risk
groups
in
1
different
geographical
areas'7
17
and
have
then
0.8
(0-5-13)
0-8
(0-4-1-7)
related
their
findings
to
OCP
use
in
addition
1-7
(1-3-2-2)*
to
other
potential
confounding
variables.
1
Although
there
was
a
trend
favouring
an
asso-
0.4
(0.3-0.6)*
ciation
between
OCP
use
and
HPV
detection,
particularly
when
oral
contraception
was
used
Chlamydia
Syphilis
Pubic
Lice
Genital
Herpes
__
__~~~~~~~~~~1
*p
<
0
05.
331
777
..--..ti
332
over
prolonged
periods,
this
failed
to
reach
statistical
significance.
However,
the
presence
of
clinically
apparent
warts
was
significantly
associated
with
long-term
(over
5
years)
OCP
use
in
a
case
control
study
from
Washington.'8
There
has
also
been
an
anecdotal
report
of
recalcitrant
genital
warts
which
regressed
after
the
withdrawal
of
oral
contraceptives.'9
The
role
of
the
OCP
in
genital
cancers
is
contro-
versial
but
may
be
protective
for
ovarian
and
endometrial
tumours202'
but
increase
the
risk
of
cervical
dysplasia
(particularly
high
grade
changes)
and
possibly
cancer.22
26
Therefore
despite
the
cross
sectional
design
of
our
study,
which
presents
difficulties
in
establishing
a
cause
and
effect
relationship,
there
is
a
biological
basis
for
oral
contracep-
tives
increasing
the
prevalence
of
clinically
apparent
genital
warts
(via
depressed
cellular
immunity)
and
a
possible
dose
response
effect
with
some
studies
suggesting
that
prolonged
exposure
is
required
before
an
effect
is
appar-
ent.
It
was
not
possible
to
control
for
all
poten-
tial
confounding
factors
owing
to
the
retro-
spective
study
design.
Although
the
length
of
time
that
each
patient
had
been
sexually
active
was
not
known
the
patient's
age
may
have
pro-
vided
an
indirect
assessment
of
this.
Age
at
first
intercourse
and
lifetime
number
of
part-
ners
could
also
not
be
compared
in
the
study
and
control
groups.
The
oestrogen
dose
in
dif-
ferent
preparations
of
OCP
may
be
relevant
to
the
risk
of
genital
warts,
as
may
the
total
length of
time
on
the
OCP
and
neither
of
these
could
be
assessed
accurately
from
the
present
study
design.
Another
potential
confounder
is
condom
use
since
those
using
the
OCP
are
less
likely
to
use
barrier
protection
and
any
effect
seen
may
reflect
the
lack
of
a
condom
rather
than
the
use
of
the
OCP.
Unfortunately
this
information
was
not
reliably
collected
in
the
casenotes.
In
restricting
the
analysis
to
genitourinary
medicine
clinic
attenders
there
is
also
a
poten-
tial
recruitment
bias
in
those
studied.
Thus
it
is
possible
that
clinic
attenders
with
genital
warts
may
differ
from
other
patients
in
the
community
with
warts
who
do
not
attend
a
GU
clinic
for
treatment.
There
is
increasing
evidence,
however,
that
sexual
behaviour
pat-
terns
and
STD
rates
differ
little
between
patients
attending
genitourinary
clinics,
family
planning
clinics
and
in
general
practice.27
29
Patients
with
genital
warts
were
twice
as
likely
not
to
admit
to
having
had
a
sexual
part-
ner
within
the
preceding
3
months.
This
may
have
been
the
result
of
embarrassment
associ-
ated
with
having
visible
signs
of
a
sexually
transmitted
infection
inhibiting
the
formation
of
new
relationships.
The
present
study
also
suggests
that
once
warts
present
clinically
patients
are
no
more,
and
possibly
less,
sexu-
ally
active
than
those
attending
the
clinic
with-
out
warts,
even
before
being
provided
with
health
education
and
advice.
The
low
preva-
lence
of
concurrent
STDs
in
patients
with
warts
compared
to
genitourinary
medicine
clinic
attenders
without
warts
also
suggests
that
this
group
may
be
less
sexually
active
or
using
additional
barrier
methods
of
contracep-
tion.
The
relatively
few
studies
that
have
assessed
the
association
between
genital
warts
and
oral
contraceptive
use
have
generally
done
so
in
a
family
planning
or
colposcopy
setting
and
although
there
is
limited
evidence
for
the
asymptomatic
detection
of
HPV
being
associ-
ated
with
taking
the
OCP,
the
evidence
from
this
and
other
studies
supports
a
limited
role
for
oral
contraceptives
in
the
prevalence
of
clinical
condylomata
acuminatum.
The
major
problem
in
interpreting
these
studies
is
the
large
number
of
other
factors
which
may
influ-
ence
the
prevalence
of
genital
warts
and
which
may
act
as
confounders
for
OCP
use.
Thus
a
prospective
trial
using
the
published
studies
as
a
basis
for
the
trial
design
and
permitting
the
inclusion
of
these
confounding
factors
is
required
to
strengthen
the
hypothetical
link
between
oral
contraceptives
and
genital
warts.
1
Ross
J.
The
changing
pattern
of
sexually
transmitted
dis-
eases
in
Scotland:
implications
for
the
spread
of
HIV.
ANSWER
1995;34:1-3.
2
Wikstrom
A,
Lidbrink
P,
Johansson
B,
von
Krogh
G.
Penile
human
papillomavirus
carriage
among
men
attending
Swedish
STD
clinics.
Int
J
STD
AIDS
199
1;2:
105-9.
3
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