Aboubakr Elnashar

1. ENDOMETRIAL
HYPERPLASIA
Guidelines
of
SOGC,
2019
Prof.
Aboubakr
Elnashar
Benha
university
hospital,
Egypt
ABOUBAKR
ELNASHAR
CONTENTS
1.
INTRODUCTION
1.
INCIDENCE
2.
RISK
FACTORS
3.
CLASSIFICATION
&
HISTOPATHOLOGY
2.
DIAGNOSIS
1.
SYMPTOMS
2.
SIGNS
3.
INVESTIGATIONS
3.
MANAGEMENT
1.
WITHOUT
ATYPIA
2.
WITH
ATYPIA
3.
IN
POLYP
❑
CONCLUSION
ABOUBAKR
ELNASHAR
3

2. INTRODUCTION
▪
Incidence
▪
increases
with
age
▪
133
per
100
000
woman-years
▪
Rarely
seen
in
women
under
the
age
of
30
▪
Its
peak
in
women
aged
50
to
54.
ABOUBAKR
ELNASHAR
▪
Risk
factors
1.
Menstrual
factors:
1.
Older
age
or
postmenopausal
status
2.
Nulliparity
or
infertility
3.
Early
menarche
or
later
menopause
4.
Anovulation
or
PCOS
2.
Iatrogenic
factors:
1.
Unopposed
exogenous
estrogen
therapy
2.
Tamoxifen
ABOUBAKR
ELNASHAR
3.
Comorbidities:
1.
Obesity:
important
risk
factor
2.
DM
3.
Hypertension
4.
Lynch
syndrome

4. ▪
Classification
&
histopathology
In
2014,
WHO
modified
the
classification
to
include
only
2
categories:
1.
Hyperplasia
without
atypia
2.
Hyperplasia
with
atypia:
▪
Atypical
hyperplasia
or
▪
Endometrial
intraepithelial
neoplasia
(EIN).
▪
Health
care
providers
should
use
the
2014
WHO
histopathologic
classification
of
endometrial
hyperplasia
(strong).
ABOUBAKR
ELNASHAR

5. ABOUBAKR
ELNASHAR
▪
Hyperplasia
without
atypia
▪
Not
share
the
same
genetic
mutations
as
its
counterpart.
▪
Rarely
progresses
to
endo
carcinoma
(1%−3%)
▪
Can
be
managed
conservatively.
ABOUBAKR
ELNASHAR
▪
Hyperplasia
with
atypia
▪
Precursor
to
type
I
endom
carcinomas
as
both
share
a
similar
profile
of
genetic
alterations
and
monoclonal
growth.
▪
60%
have
already
developed
or
will
develop
endometrial
cancer.
▪
More
definitive
treatment
approach

6. DIAGNOSIS
❑
Symptoms
▪
In
premenopausal
women:
▪
AUB:
▪
Disturbances
in
regularity,
frequency,
duration&
heaviness
of
menstrual
bleeding
▪
Intermenstrual
bleeding
(IMB)
▪
Risk
of
endom
carcinoma
is
higher
with
IMB
compared
with
HMB
▪
Postmenopausal
bleeding
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ELNASHAR
❑
Physical
Findings
▪
Can
be
normal
or
▪
Obesity
▪
Features
of
PCOS.
▪
Bimanual
exam
of
the
uterus
▪
Speculum
exam
for
Pap
testing
ABOUBAKR
ELNASHAR

7. ❑
Investigation:
1.
Endometrial
tissue
sampling
▪
Indication:
Any
woman
with
suspected
endometrial
hyperplasia
or
endometrial
cancer
▪
40
ys
or
older
▪
BMI
of
30
kg/m
2
or
greater
(moderate).
▪
No
response
to
medical
therapy
▪
Young
women
based
on
their
risk
factors.
▪
Using
a
Pipelle
device
in
an
outpatient
setting
is
the
most
appropriate
first
step
for
diagnosis
(strong,
high).
ABOUBAKR
ELNASHAR
Endocurette
Pipelle

8. 2.
Hysteroscopy
with
directed
sampling
&
curettage
▪
The
preferred
method
of
investigation
in.
1.
Non-diagnostic
or
benign
endometrial
sample
with
remaining
high
suspicion
of
endometrial
hyperplasia
or
cancer
2.
Cervical
stenosis,
failed
endometrial
biopsy
3.
Persistent
bleeding,
or
excessive
pain/anxiety
4.
Recurrent
symptoms
of
AUB
after
initial
observation
or
medical
treatment
(strong,
high).
ABOUBAKR
ELNASHAR
▪
Risk
of
Tumour
Spillage
▪
Through
Hysteroscopy
or
Saline
Infusion,
there
were
concerns
about
tumour
spillage
and
cancer
upstaging
in
women
previously
investigated
with
hysteroscopy
or
saline
US
for
endometrial
hyperplasia
or
cancer.
▪
There
is
no
study
showing
any
adverse
outcome
for
patients
with
a
previous
endoscopic
diagnostic
procedure.
▪
Since
2014,
peritoneal
washing
has
not
been
part
of
the
International
Federation
of
Gynecology
and
Obstetrics
staging
for
endometrial
cancer.
ABOUBAKR
ELNASHAR

9. MANAGEMENT
▪
Addressing
the
Risk
Factors
▪
Encouraging
obese
to
lose
weight.
▪
Correction
of
those
medical
conditions
(strong,
high)..
ABOUBAKR
ELNASHAR
I.
ENDOMETRIAL
HYPERPLASIA
WITHOUT
ATYPIA
1.
Conservative
Management
▪
Supported
by
1.
Long-term
risk
for
progression
to
endomet
carcinoma≤5%
2.
Spontaneous
regression
rates
of
75
to
100%.
2.
Hormonal
TT
▪
Indication:
▪
Hyperplasia
does
not
resolve
with
observation
▪
AUB
(weak,
low).
▪
Majority
of
cases
are
successfully
managed
medically
▪
Hysterectomy
is
not
considered
first-line
TT
&
is
reserved
for
specific
circumstances
(moderate).
ABOUBAKR
ELNASHAR

10. 1.
Levonorgestrel
IUD
should
be
1
st
line
TT
due
to:
1.
Its
effectiveness
(81%
to
94%
regression)
2.
Favourable
side
effect
profile
(strong,
high)
3.
It
can
be
kept
in
place
for
5
y
in
patients
showing
TT
response
(strong,
moderate).
▪
Treating
pre
&
postmenopausal
women
▪
Follow-up
by
▪
endometrial
sampling
▪
performed
with
the
IU
device
in
place
ABOUBAKR
ELNASHAR
2.
Progrstins:
▪
Low-dose
oral
(regression
rate
67
to72%)
and
▪
Injectable
progestins
(DMP:
regression
rate
after
6
m:
92%)
remain
an
acceptable
TT
option
for
endometrial
hyperplasia
with
&
without
atypia
desiring
an
alternative
TT
modality
(strong,
high).
▪
Treating
both
pre
&
postmenopausal
women
ABOUBAKR
ELNASHAR

11. ▪
Oral
progestins:
start
on
a
low
dose
for
a
minimum
of
6
months.
▪
Assessment
of
the
endometrium
Endometrial
biopsy
(strong,
very
low).
▪
Mid-therapy
after
3
months
▪
3
w
after
completion
of
TT
to
ensure
proper
interpretation
▪
Relapse
rate
is
higher
in
patients
▪
Treated
with
progestins
▪
Those
with
a
BMI
35
kg/m
2
.
▪
The
follow-up
duration
for
those
patients
should
therefore
be
extended.
ABOUBAKR
ELNASHAR
3.
Aromatase
inhibitors
▪
An
effective
TT
option
for
patients
with
endometrial
hyperplasia
without
atypia.
▪
Letrozole
▪
comparable
effectiveness
to
megestrol
acetate
▪
favourable
side
effect
profile
▪
used
in
pre
&
postmenopausal
women.
ABOUBAKR
ELNASHAR

12. Dydrogesterone
10
mg,
2
tablets
twice
daily
from
fifth
day
of
menstruation
for
21
days
for
6
months
ABOUBAKR
ELNASHAR
3.
Surgical
Treatment
▪
Indication:
1.
Persistent
(fails
to
regress
after
12
months)
or
Recurrent
hyperplasia
despite
progestin
use
2.
Progression
to
atypical
hyperplasia
or
carcinoma
3.
Ongoing
AUB
despite
TT
4.
Patient
preference.
5.
Contraindication
or
intolerance
to
medical
TT
6.
Unwillingness
to
comply
with
surveillance
7.
No
desire
for
future
fertility
8.
High
baseline
risk
for
endometrial
carcinoma.
ABOUBAKR
ELNASHAR

13. ▪
Total
hysterectomy
with
opportunistic
salpingectomy,
with
bilateral
oophorectomy
in
postmenopause
&
(strong,
moderate)
&
▪
without
oophorectomy
in
premenopausal
women
{increased
mortality
&
morbidity
associated
with
removal
of
the
ovaries
in
young
women
with
benign
disease}
(moderate).
▪
Surgical
approach
▪
Vaginal,
laparoscopic,&
open
approaches
are
all
acceptable
{it
is
considered
non-neoplastic
entity},
▪
Vag
or
laparoscopic
route:
fewer
perioperative
complications
ABOUBAKR
ELNASHAR
4.
Endometrial
Ablation
▪
There
is
insufficient
evidence
to
support
as
first-lineTT
except
in
circumstances
where
major
surgery
is
contraindicated
(low).
▪
Safe
option
for
treatment
▪
Limitation
1.
Difficulty
in
confirming
complete
destruction
of
the
endometrium.
2.
Surveillance
can
be
challenging
due
to
obliteration
of
the
endometrial
cavity
▪
Patients
should
be
followed
up
at
regular
intervals&
investigated
if
AUB
persists
or
recurs.
ABOUBAKR
ELNASHAR

14. II.
ATYPICAL
ENDOMETRIAL
HYPERPLASIA/EIN
1.
Hysterectomy
&
Bilateral
Salpingo-oophorectomy
▪
are
the
recommended
TT
in
pre&postmenopausal
{underlying
risk
of
malignancy
or
progression
to
endometrial
cancer.
60%
of
patients
with
EIN
already
have
developed
or
will
develop
an
invasive
endometrial
cancer}
▪
Retention
of
ovaries
in
premenopausal
may
be
considered
(low).
▪
The
increased
risk
of
mortality&morbidity
associated
with
bilateral
oophorectomy
in
premenopausal
women
with
benign
disease
should
be
discussed
thoroughly
▪
TT
tailored
to
each
individual.
ABOUBAKR
ELNASHAR
▪
Laparoscopic
hysterectomy
is
preferred
for
endometrial
hyperplasia
as
it
decreases
perioperative
morbidity&
mortality
(high)
▪
Laparotomy
limited
to
cases
where
this
is
not
feasible.
▪
Laparoscopy
vs
laparotomy:
▪
fewer
perioperative
complications,
shorter
hospital
stay,
quicker
return
to
normal
activity
▪
Survival
outcomes
are
similar
▪
Evaluation
of
the
adnexa&
other
pelvic
structures
for
signs
of
invasive
disease.
{Atypical
endometrial
hyperplasia
is
associated
with
higher
risk
of
underlying
carcinoma}
ABOUBAKR
ELNASHAR

15. ▪
Not
recommended:
1.
Subtotal
hysterectomy
&
morcellation
(strong,
low)
due
to
concern
about
malignancy
&
dissemination
of
disease
2.
Routine
intraoperative
frozen
section
analysis
(low)
3.
Routine
lymphadenectomy
(moderate).
ABOUBAKR
ELNASHAR
▪
Endometrial
Ablation
is
generally
avoided
in
patients
with
atypical
hyperplasia
because
it
is
a
pre-malignant
condition.
ABOUBAKR
ELNASHAR

16. ▪
Fertility
preservation
TT
of
EIN:
▪
Options:
1.
Oocyte
or
embryo
cryopreservation
prior
to
hysterectomy
with
BSO
2.
Hysterectomy
with
ovarian
preservation&
future
use
of
a
surrogate.
3.
Medical
TT
followed
by
ART
▪
Encourage
to
maintain
a
BMI
below
30
kg/m
2
,
as
relapse
is
much
more
common
in
obese
patients.
ABOUBAKR
ELNASHAR
▪
Cancer
incidence
does
not
increase
when
comparing
patients
undergoing
primary
hysterectomy&
delayed
hysterectomy
for
fertility-sparing
purposes.
▪
Infertility
TT
do
not
increase
the
relapse
rate
of
EIN.
▪
LBR
associated
with
conservative
TT
of
EIN:
7-
26%
▪
Pregnancy:
lower
chance
of
disease
recurrence.
▪
Hysterectomy
with
BSO
is
recommended
when
childbearing
is
no
longer
desired
{The
risk
of
disease
recurrence
being
high}
ABOUBAKR
ELNASHAR

17. 2.
Medical
treatment
options
&
follow-up
▪
Uterine
preservation
may
be
considered
in
1.
Patients
who
wish
to
preserve
their
fertility
or
2.
Who
are
medically
unfit
for
surgery.
▪
Counselling:
Important
▪
should
include
1.
Risks
of
1.
Endometrial
cancer
higher
than
stage
I
(2%)
2.
Coexisting
ovarian
cancer
(4%)
3.
Death
(0.5%)
2.
Those
outcomes
could
not
easily
be
predicted
by
pre-
treatment
investigations.
ABOUBAKR
ELNASHAR
▪
Conservative
treatment
options
▪
Progestins
(oral
or
local)
▪
Aromatase
inhibitors,
or
▪
GnRHa.
▪
Table
shows
types
of
progestins
and
dosages
that
can
be
used
in
treatment
of
EIN.
ABOUBAKR
ELNASHAR

18. ▪
Metformin
▪
May
also
be
added
to
increase
TT
effect,
even
in
the
absence
of
metabolic
syndrome.
▪
Obesity:
lower
chance
of
disease
remission.
▪
A
trial
of
6
months
▪
is
generally
necessary
to
see
TT
response,
with
a
plateau
at
around
12
months.
▪
Regression
rates:
55%
to
92%
▪
Recurrence
rates:
3%
to
55%
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
▪
Metformin
anticancer
effect:
▪
Affects
endometrial
maturation,
proliferation&
implantation.
▪
Delay
estrogen-mediated
endometrial
proliferation

19. ▪
Endometrial
biopsy
▪
Every
3
months
until
at
least
2
negative
specimens
are
obtained.
▪
The
highest
risk
of
recurrence
in
the
first
2
ys
after
treatment
cessation
▪
Every
6
months
for
2
years
and
▪
Every
year
thereafter
until
▪
Risk
factors
are
corrected
or
▪
Total
hysterectomy
with
BSO
is
performed.
ABOUBAKR
ELNASHAR
▪
Definitive
surgical
treatment
indicated
if
1.
Progression
to
carcinoma
during
follow-up,
2.
Hyperplasia
fails
to
regress
after
12
months
of
medical
TT
3.
Relapses
after
TT
with
progestins
4.
Continuous
AUB
despite
treatment
5.
Decline
of
surveillance
or
medical
TT
ABOUBAKR
ELNASHAR

20. Endometrial
Hyperplasia
in
an
Endometrial
Polyp
1.
Should
be
treated
acc
to
its
histologic
classification.
2.
Sampling
of
the
background
endometrium,
even
when
its
hysteroscopic
appearance
is
normal.
Why?
▪
Endom
hyperplasia
either
with
or
without
atypia
will
be
found
in
background
endometrium
in
up
to
52%
▪
Risk
of
concurrent
endom
cancer
in
patients
found
to
have
an
atypical
endometrial
polyp:
5.6%.
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
TAKE
HOME
MESSAGE
I.
Introduction:
▪
Risk
factors:
obesity
is
important
risk
factor
▪
Classification:
hyperplasia
without
atypia
&
with
atypia
II.
Diagnosis:
▪
Endometrial
tissue
sampling
if
suspected
end
hyperplasia
▪
Hysteroscopy
if
persistent
bleeding
III.
Management
▪
First
line
▪
Without
atypia:
Hormonal
TT
▪
With
atypia:
Hysterectomy
with
BSO