Aims of study
Genuine
stress
incontinence
(GSI),
a
common
gynaecological
condition,
is
frequently
due
to
bladder
neck
hypermobility
caused
by
a
weakness
in
the
supporting
structures
of
the
pelvic
floor.
Its
aetiology
is
almost
certainly
multifactorial.
Collagen,
a
fibrous
protein,
forms
the
major
structural
component
of
vaginal
epithelium
and
imparts
tensile
strength
to
the
tissue.
A
significant
reduction
in
total
collagen,
of
vaginal
tissue,
has
been
demonstrated
in
nulliparous
premenopausal
women
when
compared
to
controls.
There
was
an
associated
reduction
in
intermolecular
collagen
cross-linking,
suggesting
that
the
underlying
defect
within
this
population
may
be
congenital
rather
than
acquired
(1).
A
similar
reduction
in
collagen
has
not
been
clearly
demonstrated
in
post
menopausal
women
with
GSI
when
compared
to
controls
however,
oestrogen
therapy
has
been
shown
to
produce
a
reduction
in
collagen
content
(2).
The
increased
incidence
of
GSI
around
the
menopause
would
suggest
an
alteration
in
collagen
metabolism
occurs
at
this
time.
We
set
out
to
further
clarify
the
pathophysiological
changes
seen
in
women
with
bladder
neck
hypermobility:
investigating
the
effect
of
menopause
and
additional
hormone
replacement
therapy
(HRT)
on
the
supporting
tissue
on
the
pelvic
floor.
Methods
Women
recruited
into
this
controlled
study
were
placed
in
three
groups:
pre
menopausal,
postmenopausal
without
HRT
and
postmenopausal
with
at
least
1
year
of
standard
HRT.
These
were
matched
with
continent
controls
in
similar
groups.
All
those
with
stress
urinary
incontinence
symptoms
had
the
diagnosis
of
GSI
confirmed
by
conventional
cystometric
testing.
The
validated
Bristol
Female
Lower
urinary
tract
symptom
questionnaire
was
used
to
exclude
urinary
incontinence
in
the
control
groups.
The
International
Continence
Society’s
female
pelvic
organ
prolapse
grading
system
was
used
to
assess
genitourinary
prolapse
and
women
were
withdrawn
with
a
score
greater
than
1.
Tissue
samples
ware
taken
peri-urethrally
from
the
anterior
vaginal
wall
using
Eppendorfer
punch
biopsy
forceps.
The
tissue
was
stored
at
–80
°C before undergoing biochemical analysis. Total collagen content was
determined
by
hydroxyproline
analysis
and
sulphated
proteoglycan
assay
using
dimethylmethylene
blue.
The
protein
content
was
assayed
by
microkjeldahl
analysis.
The
data
underwent
analysis
of
variance
using.
Further
analysis
of
glycation
end
products
and
proteinase
activity
is
taking
place.
Results
There
were
116
women
recruited
into
this
study,
58
women
in
the
incontinence
group
and
58
in
the
control
group.
In
the
incontinence
group:
28
were
premenopausal
with
a
mean
age
43
years
(range
26-53),
14
were
post
menopausal
without
HRT
with
mean
age
59
years
(range
48-77)
and
the
14
in
the
postmenopausal
group
with
HRT
had
a
mean
age
of
56
years
(range
46-63).
In
the
control
group:
28
were
premenopausal
with
a
mean
age
41
years
(range
28-56),
14
were
post
menopausal
without
HRT
with
mean
age
61
years
(range
52-73
)
and
the
14
in
the
postmenopausal
group
with
HRT
had
a
mean
age
of
60
years
(range
53-68).
|
|
Control
|
|
GSI
|
|
|
|
Collagen
(%)
|
Proteoglycans
(mg/g)
|
Collagen
(%)
|
Proteoglycans
(mg/g)
|
|
Premenopausal
|
51.2
(± 14)
|
8.6
(± 0.3)
|
38.4
(± 11) *
|
9.6
(± 0.6) †
|
|
Postmenopausal No HRT
|
68.8
(± 18)
|
8.3
(± 0.5)
|
60.2
(± 13) *
|
10.4
(± 0.6) †
|
|
Postmenopausal with HRT
|
61.38
(± 23)
|
8.7
(± 0.3)
|
48.1
(± 13) *
|
9.6
(± 0.4) †
|
* Collagen in the GSI groups
was
lower
than
controls
(p<0.001),
postmenopausal
women
had
higher
collagen
concentration
(p<0.001)
and
HRT
caused
a
reduction
in
collagen
content
(p=0.017).
†
Poteoglycan
levels
were
higher
in
the
GSI
group
throughout
(p<0.001).
Both
groups
reacted
differently
to
the
menopause
(p=0.004)
and
to
additional
HRT
(p=0.007).
The
protein
content
of
the
tissue
was
lower
in
the
GSI
group
except
in
the
postmenopausal
group
when
the
GSI
group
fell
and
control
group
incresed
however,
this
difference
was
significant
(p=0.02).
Conclusion
We
have
confirmed
previous
findings
that:
GSI
is
associated
with
a
reduction
in
total
collagen,
of
premenopausal
vaginal
skin,
when
compared
to
controls.
In
addition
we
have
shown
this
reduction
in
collagen
is
also
present
between
postmenopausal
women
and
controls
and
verified
that
oestrogen
therapy
produces
a
fall
in
collagen
in
postmenopausal
women.
Our
findings,
although
surprising,
suggest
that
the
reduction
in
total
collagen
associated
with
HRT
may
actually
indicate
an
attempt,
by
the
tissue,
to
return
to
its
premenopausal
collagen
state.
The
collagen
and
elastin
fibres
of
the
ECM
are
embedded
in
an
amorphous
ground
substance,
of
which
proteoglycans
are
a
constituent,
which
is
essential
for
tissue
organisation.
The
increase
in
proteoglycans,
and
associated
reduction
of
collagen,
in
the
GSI
group
may
indicate
a
dilutional
effect
within
the
tissue.
Interestingly,
the
ground
substance
in
both
groups
appears
to
react
differently
to
HRT
possibly
demonstrating
an
alteration
in
metabolism
between
the
two
groups.
We
intend
to
present
additional
findings,
using
indicators
of
collagen
metabolism,
to
explain
the
changes
seen
between
these
groups.
1.
Br J Obstet Gynaecol 1997; 104:994-997.
2.
Neurourol Urodynam 1996; 15:327-8.
