Endometrial hyperplasia - irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium Endometrial Ca - most common gynaecological maglinancy in the western country, endometrial hyperplasia as the precursor Incidence of endometrial hyperplasia 3 folds higher than endometrial Ca Fourth most common cancer in women in Peninsular Malaysia

1. Management of
Endometrial Hyperplasia
MO Presentation
May 2016
By Winnie Cristal

2. Introduction
 Endometrial hyperplasia
 irregular proliferation of the endometrial glands with an increase in the gland to
stroma ratio when compared with proliferative endometrium
 Endometrial Ca
 most common gynaecological maglinancy in the western country, endometrial
hyperplasia as the precursor
 Incidence of endometrial hyperplasia 3 folds higher than endometrial Ca
 Fourth most common cancer in women in Peninsular Malaysia [1]

3. Risks factors
 when estrogen, unopposed by progesterone, stimulates
endometrial cell growth by binding to estrogen receptors in the
nuclei of endometrial cells
 Increased BMI
 Anovulation associated with perimenopause or PCOS
 Estrogen secreting ovarian tumour (eg: granulosa cell tumour)
 Drug induced endometrial stimulation (eg: use of systemic estrogen
replacement therapy/ long term tamoxifen)
 Immunosuppression and infection

4. Classification
 WHO classification of 1994
1. simple hyperplasia without atypia,
2. complex hyperplasia without atypia,
3. simple atypical hyperplasia,
4. complex atypical hyperplasia
 EIN (Endometrial intraepithelial) classification system 2003
 Benign (endometrial hyperplasia)
 Premalignant (diagnosis of EIN based upon 5 subjective histological criteria)
 Malignant (endometrial Ca)
 Latest WHO classification in 2014
 Endometrial hyperplasia without atypia
 Endomterial hyperplasia with atypia/endometrioid intraepithelial neoplasm

5. Diagnostic and surveillance methods
 Histology examination – endometrial sampling (outpatient/GA)
 TVS in pre- and postmenopausal women
 Systemic review – 3-4mm cut off, probability of Ca <1% when ET less than the cut off
 RCOG - <7mm, endometrial is unlikely
 Hysteroscopy
 CT/MRI
 CT – not recommended
 MRI – more evidence needed for surveillance of atypical endometrial hyperplasia in
predicting malignant changes
 phosphatase and tensin homolog (PTEN), perhaps in combination with B-cell
lymphoma 2 (BCL-2) and BCL-2-like protein 4 (BAX) could be potentially useful
 More research evidence needed

6. Endometrial Hyperplasia
Without Atypia With Atypia
Total hysterectomy
-TAH/TLH
Premenopausal – total hysterectomy
+ BSO +/- ovarian conservation
Post menopausal – Total
hysterectomy + BSO
Conservative
Counseling
Identify and address risk factor
Observation
- F/up with endometrial biopsies
Failed to regress/
symptomatic with AUB
Progestogen
LNG-IUS
(Mirena)
Continuous oral
progestogen
•Medroxyprogesteron
•Norestherone
Regress
- At least 2 consecutive
6 monthly NEGATIVE
biopsies prior discharge
Higher risks of relapse – 2
consecutive negative
biopsies then long term f/up
with annual endometrial
biopsy
↓ ↓
↓
↓
↙
↙ ↘
↘
 Minimum of
6month treatment
 Minimum 6
monthly
endometrial biopsy
till 2 consecutive
Negative biopsies

7. Endometrial Hyperplasia without Atypia

8. Initial management
 Counselling
 Progression to endometrial Ca <5% over 20 years
 Majority of cases regress spontaneously during f/up (74%-81% in 2 cohort studies)
 Identify and address reversible risk factor
 HRT usage
 Obesity
 Observation with f/up endometrial biopsies
 Inform patient higher regression rate with progestogens as compared to
observation alone
 Progestogens treatment
 Failed to regress following observation
 Symptomatic with AUB

9. 1st
line medical treatment
LNG-IUS (Mirena) – higher disease regression rate, fewer side effects
Continuous oral progestogen – if declined Mirena
Duration of treatment and f/up
LNG-IUS/ oraly progestogen – minimum of 6/12
LNG-IUS is encouraged to retained up to 5 years if no fertility concern
Endometrial surveillance – minimum 6 monthly, at least 2 consecutive 6monthly
negative biopsies prior discharge
 Seek referral if AUB recurs after completion of treatment – relapse
Higher risks of relapse (eg: BMI >35, treatment wirh oral progestogen)
– 2 consecutive negative biopsies then long term f/up with annual endometrial
biopsy

10. Surgical management
 NOT as first line treatment
 Indicated in women who not wanting to preserve fertility
(i) Progression to atypical hyperplasia occurs during follow-up
(ii) No histological regression of hyperplasia despite 12 months of treatment
(iii) Relapse of endometrial hyperplasia after completing progestogen treatment
(iv) there is persistence of bleeding symptoms
(v) the woman declines to undergo endometrial surveillance or comply with medical
treatment
 Postmenopausal – TAHBSO
 Premonopausal – TAH/TLH + Bilateral salphingectomy (recommended) +/-
ovarian conservation
 Endometrial ablation – not recommended (persistent endometrial destruction,
endometrial adhesion preclude future endometrial surveillance

11. Atypical Endometrial Hyperplasia

12. Initial management
 Total hysterectomy (suprecervical hysterectomy should
not be perform)
 Laparoscopic approach is preferable
 No benefit from intra-op frozen section analysis of
endometrium or routine lymphadenectomy
 Post menopausal – TAH + BSO
 Premenopausal – TAH + bilateral salphingesctmy +/-
ovarian conservation
 Endometrial ablation – not recommended

13. Management for those who wish to preserve
fertility/not suitable for surgery
 Women wishing to retain their fertility
 counsel about the risks of underlying malignancy and subsequent progression to
endometrial cancer
 Pretreatment investigations
 aim to rule out invasive endometrial cancer or co-existing ovarian cancer
 Histology, imaging and tumour marker results
 To be review in a multidisciplinary meeting for a plan of management and subsequent
endometrial surveillance
 First line treatment
 LNG-IUS
 Second best alternative
 oral progestogens
 Once fertility is no longer required
 hysterectomy - in view of the high risk of disease relapse

14. Follow up on women not
undergoing hysterectomy
 Those cases are best to be discuss in a gynaecological oncology
multidisciplinary meeting
 Review every 3 monthly with endometrial surveillance until 2 consecutive
negative biopsies
 Review schedules to be individualized according to women’s clinical condition
 Asymptomatic women + evidence of histological disease regression and
minimum of 2 consecutive negative endometrial biopsies
 Long term follow up with biopsy 6-12 monthly until hysterectomy done
 If fertility therapy failed to induce regression of the disease by 12 months,
strongly recommended for hysterectmy

15. Management of women
wishing to conceive
 Disease regression should be achieved on at least one endometrial
sample before women attempt to conceive.
 Referral to a fertility specialist to discuss the options for attempting
conception, further assessment and appropriate treatment.
 Aim for BMI < 30 for obese women
 Assisted reproduction may be considered as
 The live birth rate is higher
 May prevent relapse compared with women who attempt natural
conception.
 Regression of endometrial hyperplasia should be achieved prior to
assisted conception
 Associated with higher implantation and clinical pregnancy rates.

16. HRT and Endometrial Hyperplasia
 Systemic estrogen-only HRT should not be used in women with a uterus
 All women taking HRT should be encouraged to report any
unscheduled vaginal bleeding promptly.
 Women with endometrial hyperplasia taking a sequential HRT
preparation who wish to continue HRT should be advised to change to
continuous progestogen intake using the LNG-IUS or a continuous
combined HRT preparation.
 Subsequent management as per recommended by the guideline.
 Women with endometrial hyperplasia taking a continuous combined
preparation who wish to continue HRT should have their need to
continue HRT reviewed
 Consider using the LNG-IUS as a source of progestogen replacement.
Subsequent management as per recommended by the guideline.

17. Management of endometrial in women on
adjuvant treatment for breast cancer
 Inform regarding the increased risks of developing
endometrial hyperplasia and Ca (Tamoxifen)
 Increase risk with both dose and duration
 Statistically significant increase risk in women age 50 and above
 Encourage them to report if any abnormal vaginal
bleeding/ discharge promptly
 Aromatase inhibitors (anastrazole, exemestane,
letrozole)
 Inform that these medication not known to increase risk of
endometrial hyperplasia and Ca

18. Prophylactic Progestogen in women
on Tamoxifen?
 Evidence of LNG-IUS prevent polyp formation and
reduce incidence of endometrial hyperplasia
 Effect of LNG-IUS on breast Ca recurrence risk uncertain, so routine
use cannot be recommended
Women who develop endometrial hyperplasia
while on Tamoxifen for breast ca
 Need for Tamoxifen to be reassess and manage accordingly
to the histological classification of endometrial hyperplasia in
conjunction with the oncologist

19. Endometrial hyperplasia confined to
an endometrial polyp
 Complete removal of the polyp + endometrial biopsy to
sample background endometrium
 Manage according to the histological classification of
endometrial hyperplasia

20. Endometrial Hyperplasia
Without Atypia With Atypia
Total hysterectomy
-TAH/TLH
Premenopausal – total hysterectomy
+ BSO +/- ovarian conservation
Post menopausal – Total
hysterectomy + BSO
Conservative
Counseling
Identify and address risk factor
Observation
- F/up with endometrial biopsies
Failed to regress/
symptomatic with AUB
Progestogen
LNG-IUS
(Mirena)
Continuous oral
progestogen
•Medroxyprogesteron
•Norestherone
Regress
- At least 2 consecutive
6 monthly NEGATIVE
biopsies prior discharge
Higher risks of relapse – 2
consecutive negative
biopsies then long term f/up
with annual endometrial
biopsy
↓ ↓
↓
↓
↙
↙ ↘
↘
 Minimum of
6month treatment
 Minimum 6
monthly
endometrial biopsy
till 2 consecutive
Negative biopsies

21. THANK YOU