Management of endometrial hyperplasia - RCOG

1. dr. Mohamed Alajami
Higher Studies in Obs.Gyne- MD
Lecturer in HAMA University
Management of Endometrial
Hyperplasia- RCOG 2016

2.  Endometrial hyperplasia is an irregular proliferation of the
endometrial glands with an increase in the gland to stroma ratio
when compared with proliferative endometrium
 The most common presentation is abnormal uterine
bleeding:
1. heavy menstrual bleeding
2. intermenstrual bleeding
3. irregular bleeding
4. unscheduled bleeding on hormone replacement therapy (HRT)
5. postmenopausal bleeding
INTRODUCTION
dr. Mohamed Alajami

3.  when estrogen, unopposed by progesterone:
1. increased body mass index (BMI)
2. anovulation associated with the perimenopause
3. polycystic ovary syndrome
4. estrogen-secreting ovarian tumors
5. drug-induced endometrial stimulation
 Immunosuppression ??
 Infection may be!!!
Risk factors for endometrial hyperplasia
dr. Mohamed Alajami

4.  Hyperplasia Without Atypia
 Atypical Hyperplasia.
 Criteria for cytologic atypia:
1. large nuclei of variable size and shape that have lost polarity
2. increased nuclear-to-cytoplasmic ratios
3. prominent nucleoli
4. irregularly clumped chromatin with parachromatin clearing
(WHO) classification 2014
dr. Mohamed Alajami

5. Normal proliferative endometrium
Normal endometrium
dr. Mohamed Alajami
Day 17 secretory endometrial glands

6. Endometrial Hyperplasia Without Atypia
dr. Mohamed Alajami

7. Atypical Endometrial Hyperplasia
dr. Mohamed Alajami

8. Atypical Endometrial Hyperplasia
dr. Mohamed Alajami

9. Atypical Endometrial Hyperplasia
with Adenocarcinoma
dr. Mohamed Alajami

10.  requires histological examination of the endometrial tissue.
 Endometrial surveillance by outpatient endometrial biopsy
 Diagnostic hysteroscopy where
 outpatient sampling fails or is nondiagnostic.
 endometrial hyperplasia diagnosed within a polyp or other discrete focal
lesion.
 Transvaginal ultrasound may have a role in pre- and
postmenopausal women.
 (CT), (MRI) or biomarkers are not routinely recommended.
diagnosis and surveillance EH
dr. Mohamed Alajami

11. © in Postmenopausal bleeding
1. irregularity of the endometrial profile or
2. abnormal double layer endometrial thickness
3. cut-off of 3 mm or 4 mm for ruling out endometrial cancer and
hyperplasia
 larger cut-off value for women taking HRT or tamoxifen
Transvaginal ultrasound scan (TVS)
dr. Mohamed Alajami

12. © The role of ultrasound in premenopausal women is restricted to
identifying structural abnormalities
© endometrial hyperplasia is unlikely in
 women with PCOS and absent withdrawal bleeds
 abnormal uterine bleeding > 7 mm
Transvaginal ultrasound scan (TVS)
dr. Mohamed Alajami

13. © Hysteroscopy nt may be necessary if
 Abnormal bleeding persists
 intrauterine structural abnormalities such as polyps are suspected on TVS
or endometrial biopsy
© hysteroscopy is more accurate in detecting than excluding
endometrial disease and has a higher accuracy for endometrial
cancer than endometrial hyperplasia
Hysteroscopy
dr. Mohamed Alajami

14. ® the risk of endometrial hyperplasia without atypia progressing to
endometrial cancer is < 5% over 20 years
® majority of cases of endometrial hyperplasia without atypia will
regress spontaneously during follow-up.
® Identify reversible risk factors such as obesity and the use of
hormone replacement therapy (HRT) .
initial management of hyperplasia
without atypia
dr. Mohamed Alajami

15. ® the risk of endometrial hyperplasia without atypia progressing to
endometrial cancer is < 5% over 20 years
® majority of cases of endometrial hyperplasia without atypia will
regress spontaneously during follow-up.
® Identify reversible risk factors such as obesity and the use of
hormone replacement therapy (HRT) .
initial management of hyperplasia
without atypia
dr. Mohamed Alajami

16. ® Observation alone with follow-up endometrial biopsies to ensure
disease regression can be considered, especially when identifiable
risk factors can be reversed.
® treatment with progestogens has a higher disease regression rate
compared with observation alone.
® Progestogen treatment is indicated in
 women who fail to regress following observation alone
 symptomatic women with abnormal uterine bleeding.
initial management of hyperplasia
without atypia
dr. Mohamed Alajami

17.  Obesity is a major risk factor
® lose weight is recommended
® bariatric surgery may reduce this risk
 exogenous hormones that includes prescribed HRT preparations:
® Review the indication and type of combined HRT regimen;
relative dosages of estrogen and progestogen
® Manipulation of the combined HRT regimen alone is often
sufficient in inducing regression of endometrial hyperplasia
without atypia
Reversible risk factors for EH
dr. Mohamed Alajami

18.  Ongoing tamoxifen treatment should be reviewed in conjunction
with the woman’s oncologist
 Anovulatory cycles in PCOS or in perimenopausal
® regress to normal once women with PCOS resume ovulation
® perimenopausal women reach the menopause
 postmenopausal bleeding with endometrial hyperplasia without
atypia will have andergone a baseline pelvic ultrasound
● exclude the possibility of an estrogen secreting granulosa cell tumour of
the ovary
Reversible risk factors for EH
dr. Mohamed Alajami

19. ●first-line medical treatment of hyperplasia without atypia
 Both continuous oral and local intrauterine (levonorgestrel-
releasing intrauterine system [LNG-IUS]) progestogens
 The LNG-IUS should be the first-line medical treatment.
 Continuous progestogens should be used for women who
decline the LNG-IUS.
• medroxyprogesterone 10–20 mg/day
• norethisterone 10–15 mg/day
≠ Cyclical progestogens should not be used because they are
less effective.
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

20. ●duration of treatment and follow-up of hyperplasia without atypia
 Treatment with oral progestogens or the LNG-IUS should be for
a minimum of 6 months in order to induce histological
regression of endometrial hyperplasia without atypia.
 If adverse effects are tolerable and fertility is not desired,
women should be encouraged to retain the LNG-IUS for up to 5
years as this reduces the risk of relapse, especially if it alleviates
abnormal uterine bleeding symptoms
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

21. ●Endometrial surveillance:
 Endometrial surveillance incorporating outpatient endometrial
biopsy is recommended after a diagnosis of hyperplasia without
atypia
 Endometrial surveillance should be arranged at a minimum of
6-monthly intervals, although review schedules should be
individualized and responsive to changes in a woman’s clinical
condition.
 At least two consecutive 6-monthly negative biopsies should be
obtained prior to discharge
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

22. ●Endometrial surveillance:
 further referral is needed if abnormal vaginal bleeding recurs
after completion of treatment because this may indicate disease
relapse.
 In women at higher risk of relapse, such as women with BMI >
35 or those treated with oral progestogens,
• 6-monthly endometrial biopsies are recommended.
• Once two consecutive negative endometrial biopsies then
long-term follow-up should be considered with annual
endometrial biopsies
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

23. ●Surgical Management:
 Hysterectomy should not be considered as a first-line treatment
for hyperplasia without atypia
 Hysterectomy is indicated in women not wanting to preserve
their fertility when:
1. progression to atypical hyperplasia occurs during follow-up
2. no histological regression of hyperplasia despite 12 months of treatment
3. relapse of endometrial hyperplasia after completing progestogen treatment
4. persistence of bleeding symptoms
5. the woman declines to undergo endometrial surveillance or comply with
medical treatment
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

24. ●Surgical Management:
 Postmenopausal women requiring surgical management for
endometrial hyperplasia without atypia should be offered a
bilateral salpingo-oophorectomy together with the total
hysterectomy.
 For premenopausal women, the decision to remove the ovaries
should be individualized; however, bilateral salpingectomy
should be considered as this may reduce the risk of a future
ovarian malignancy.
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

25. ●Surgical Management:
 A laparoscopic approach to total hysterectomy is preferable
 Endometrial ablation is not recommended for the treatment of
endometrial hyperplasia because
1. complete and persistent endometrial destruction cannot be ensured
2. intrauterine adhesion formation may preclude future endometrial
histological surveillance
Treatment of hyperplasia without atypia
dr. Mohamed Alajami

26. ® initial management of atypical hyperplasia should be a total
hysterectomy because of the risk of underlying malignancy or
progression to cancer
® The cumulative risk of cancer
• 8% in 4 years
• 12.4% after 9 years
• 27.5% after 19 years
• Atypical hyperplasia associated with a rate of concomitant carcinoma of
up to 43% in women undergoing hysterectomy
management of atypical hyperplasia
dr. Mohamed Alajami

27. ® initial management of atypical hyperplasia should be
● Postmenopausal women with atypical hyperplasia should be
offered bilateral salpingo-oophorectomy together with the
total hysterectomy
● For premenopausal women, the decision to remove the
ovaries should be individualized; however, bilateral
salpingectomy should be considered as this may reduce the
risk of a future ovarian malignancy
● Endometrial ablation is not recommended
management of atypical hyperplasia
dr. Mohamed Alajami

28. ● For premenopausal women,
risks of surgical menopause should be balanced against the risk of
underlying cancer and the need for further surgery to remove the ovaries
who undergo hysterectomy and bilateral salpingo-oophorectomy
should consider the use of estrogen replacement until the age of
the natural menopause
● Due to the risks of disseminating malignancy, morcellation of the
uterus should be avoided.
● Supracervical hysterectomy should not be performed
management of atypical hyperplasia
dr. Mohamed Alajami

29. ● A laparoscopic approach to total hysterectomy is preferable
● There is no benefit from intraoperative frozen section analysis of
the endometrium or routine lymphadenectomy
management of atypical hyperplasia
dr. Mohamed Alajami

30. ● wish to preserve their fertility or who are not suitable for surgery:
 should be counselled about the risks of underlying malignancy and
subsequent progression to endometrial cancer
 rule out invasive endometrial cancer or co-existing ovarian cancer
 Histology, imaging and tumour marker results should be reviewed in
a multidisciplinary meeting and a plan for management and ongoing
endometrial surveillance formulated
management of atypical hyperplasia
dr. Mohamed Alajami

31. ● wish to preserve their fertility or who are not suitable for surgery:
 First-line treatment with the LNG-IUS should be recommended, with
oral progestogens as a second-best alternative and then
aromatase inhibitors and gonadotrophin-releasing
hormone agonists
 Once fertility is no longer required, hysterectomy should be offered
in view of the high risk of disease relapse
management of atypical hyperplasia
dr. Mohamed Alajami

32.  How should women with atypical hyperplasia not undergoing
hysterectomy be followed up?
● Routine endometrial surveillance include endometrial biopsy.
● Review schedules should be individualized and be responsive to
changes in a woman’s clinical condition.
● Review intervals should be every 3 months until two consecutive
negative biopsies are obtained.
management of atypical hyperplasia
dr. Mohamed Alajami

33.  How should women with atypical hyperplasia not undergoing
hysterectomy be followed up?
● In asymptomatic women with a uterus and evidence of histological
disease regression, based upon a minimum of two consecutive
negative endometrial biopsies, long-term follow-up with
endometrial biopsy every 6–12 months is recommended until a
hysterectomy is performed.
management of atypical hyperplasia
dr. Mohamed Alajami

34.  Disease regression should be achieved on at least one endometrial
sample before women attempt to conceive
 Women with endometrial hyperplasia who wish to conceive should
be referred to a fertility specialist to discuss the options for
attempting conception, further assessment and appropriate
treatment
Management of EH in women wishing
to conceive
dr. Mohamed Alajami

35.  Assisted reproduction may be considered as the live birth rate is
higher and it may prevent relapse compared with women who
attempt natural conception
 Immediate assisted reproductive technology avoids a prolonged
interval of time without progestogen treatment, which could
cause women to relapse
 Prior to assisted reproduction, regression of endometrial hyperplasia
should be achieved as this is associated with higher implantation
and clinical pregnancy rates
Management of EH in women wishing
to conceive
dr. Mohamed Alajami

36.  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
dr. Mohamed Alajami

37.  Women with endometrial hyperplasia taking a continuous combined
preparation who wish to continue HRT should
 have their need to continue HRT reviewed.
 Discuss the limitations of the available evidence regarding the
optimal progestogen regimen in this context.
 Consider using the LNG-IUS as a source of progestogen
replacement.
dr. Mohamed Alajami

38.  the risk of developing endometrial hyperplasia on adjuvant
treatment for breast cancer:
 tamoxifen increases risks of developing endometrial hyperplasia and
cancer.
 They should be encouraged to report any abnormal vaginal
bleeding or discharge promptly
 aromatase inhibitors (anastrozole, exemestane and letrozole) are not
known to increase the risk of endometrial hyperplasia and cancer.
Management of EH in women on
adjuvant treatment for breast cancer?
dr. Mohamed Alajami

39.  Tamoxifen:
 Tamoxifen is a selective estrogen receptor modulator inhibits
proliferation of breast cancer by competitive antagonism at
estrogen receptors.
 it has a partial agonist action on other tissues, including the
vagina and the uterus.
 The risk increases with both dose and duration of treatment.
Management of EH in women on
adjuvant treatment for breast cancer?
dr. Mohamed Alajami

40.  Tamoxifen:
 The ability of tamoxifen to induce endometrial cancer and other
pathologies varies between pre- and postmenopausal women
• risk is not significant in women aged <49,
• significant increase in risk in women aged 50 years or older.
Management of EH in women on
adjuvant treatment for breast cancer?
dr. Mohamed Alajami

41.  Aromatase inhibitors:
 inhibit estrogen synthesis in the peripheral tissues and have a
similar tumor-regressing effect to tamoxifen
 do not increase the risk of endometrial pathology or vaginal
bleeding
 Aromatase inhibitors have also been explored as a treatment
option for endometrial hyperplasia
Management of EH in women on
adjuvant treatment for breast cancer?
dr. Mohamed Alajami

42.  LNG-IUS prevents polyp formation and reduces the incidence of
endometrial hyperplasia in women on tamoxifen.
 Effect of the LNG-IUS on breast cancer recurrence risk uncertain so
its routine use cannot be recommended.
Should women on tamoxifen be treated
with prophylactic progestogen therapy?
dr. Mohamed Alajami

43.  The need for tamoxifen should be reassessed and
 management should be according to the histological classification of
endometrial hyperplasia and in conjunction with the woman’s
oncologist
How should women who develop EH while on
tamoxifen for breast cancer be managed?
dr. Mohamed Alajami

44.  Complete removal of the uterine polyp(s) is recommended and an
endometrial biopsy should be obtained to sample the background
endometrium
 Subsequent management should be according to the histological
classification of endometrial hyperplasia.
Management of EH confined to an
endometrial polyp
dr. Mohamed Alajami

45.  100% of women with endometrial hyperplasia with a BMI greater
than 30 should be advised to lose weight.
 100% of women with endometrial hyperplasia without atypia should
have at least two negative endometrial biopsies prior to discharge.
 100% of postmenopausal women with atypical hyperplasia should
undergo a total hysterectomy and bilateral salpingo-oophorectomy
if not medically contraindicated
Conclusion
dr. Mohamed Alajami

46.  The role of clinical factors and biomarkers in the diagnosis and
follow-up of endometrial hyperplasia.
 The effect of weight loss, community-based obesity services, lifestyle
programs and bariatric surgery on regression of endometrial
hyperplasia.
 The optimal duration of oral and local progestogen treatment for
endometrial hyperplasia to induce and maintain disease regression.
????
dr. Mohamed Alajami

47.  Evaluation of endometrial surveillance regimens.
 Prospective long-term follow-up of women observed or treated for
endometrial hyperplasia to provide more precise estimates of the
natural history of endometrial disease and to delineate risk factors
predictive of disease persistence, progression and relapse.
 The role of the LNG-IUS in HRT-associated endometrial hyperplasia
and whether it is safe to restart HRT once hyperplasia has been
successfully treated.
????
dr. Mohamed Alajami

48. dr. Mohamed Alajami
Have a nice dayHave a nice day