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Title of Guideline (must include the word Guideline (not protocol,

policy, procedure etc) GUIDELINE FOR THE MANAGEMENT OF


ENDOMETRIAL HYPERPLASIA
Author: Contact Name and Job Title
Dr Elijah Macowvic, ST3, Obstetrics and
Gynaecology

Dr Ayesha Khaleel, F1

Mr David Nunns, Consultant Gynaecological


Oncologist, NUH

Directorate & Speciality Family Health

Date of submission

Explicit definition of patient group to which it applies (e.g. Adult women with histological diagnosis of
inclusion and exclusion criteria, diagnosis) endometrial hyperplasia

Version 1

If this version supersedes another clinical guideline please be


explicit about which guideline it replaces including version
number.
Statement of the evidence base of the guideline has the
guideline been peer reviewed by colleagues? 1

Evidence base: (1-6) Royal College of Obstetricians and


1 NICE Guidance, Royal College Guideline, SIGN Gynaecologists. Green top guideline No. 67
(please state which source). Management of Endometrial Hyperplasia.
2a meta analysis of randomised controlled trials RCOG/BSGE London. 2016.
2b at least one randomised controlled trial
3a at least one well-designed controlled study without https://www.rcog.org.uk/globalassets/documents/
randomisation guidelines/green-top-
3b at least one other type of well-designed quasi- guidelines/gtg_67_endometrial_hyperplasia.pdf
experimental study
4 well designed non-experimental descriptive
studies (ie comparative / correlation and case
studies)
5 expert committee reports or opinions and / or
clinical experiences of respected authorities
6 recommended best practise based on the clinical
experience of the guideline developer
Consultation Process Family Health guidelines group

Ratified by: David Nunns, Gynae Guideline Lead

Date: 8.4.17
Target audience General gynaecologists (all grades) at NUH

Review Date: (to be applied by the Integrated Governance Team) 08/04/2022

A review date of 5 years will be applied by the Trust. Directorates


can choose to apply a shorter review date, however this must be
managed through Directorate Governance processes.

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The
interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If
in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date.

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Algorhythm for the management of endometrial hyperplasia without atypia

Histological diagnosis of endometrial


hyperplasia without atypia

Inform

Tell the patient that the risk of endometrial hyperplasia without atypia progressing to
endometrial cancer is less than 5% over 20 years and that many cases will
spontaneously regress.
Advise that treatment with progestogens has a higher disease regression and we
recommend progestogen treatment. Discuss ways to reduce their risk factors such
as losing weight and stopping any oestrogenic treatments.

Treatment

Progestogen treatment is the preferred option


o Levonorgestrel-releasing intrauterine system (MIRENA) as first line or
o Continuous oral progestogens such as medroxyprogesterone 10 - 20mg per
day or Norethisterone 10 - 15mg per day if an intrauterine system is declined.
Advise them about reducing their risk factors (eg weight loss)
Optimise the management of PCOS if appropriate
All patients should have a pelvic ultrasound scan to exclude ovarian tumours.

Follow up

Progestogen treatments should be given for at least 6 months then rebiopsy in clinic
(Pipelle) to ensure histological reversal.
Two consecutive negative biopsies at least 6 months apart should be obtained prior
to discharge.
Women who have a LNG-IUS (such as MIRENA) and are satisfied with it, can be
advised to continue with this treatment for 4 years.
If EH has not regressed after 6 months of treatment, women should be offered a
further 6 months treatment with oral progestogens or LNG-IUS then rebiopsy 6
months later. If EH persists after the second course of treatment, surgical
management may be offered if preservation of the uterus is not desired. If
preservation of the uterus is desired then refer to the Gynaecology Oncology team
for further assessment and counselling.

Surgical management

Hysterectomy is indicated in women who do not wish or need to preserve their fertility when:

Progression to atypia occurs during follow up


There is no histological regression of hyperplasia despite 12 months of treatment
There is relapse of endometrial hyperplasia after completing progestogen treatment
There is persistence of bleeding symptoms
Endometrial surveillance and medical treatment is declined

Endometrial ablation is not recommended

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Algorhythm for the management of endometrial hyperplasia with atypia

Histological diagnosis of endometrial


hyperplasia with atypia (Discuss all
cases at gynae cancer MDT)

Is fertility or preservation of
uterus required?

NO YES

Recommend total laparoscopic Refer to gynaecology oncology


hysterectomy. for further counselling and
management.
Bilateral salpingo-oopherectomy
should also be performed in
postmenopausal women and
considered in pre-menopausal
women. Individualised care plan should be
If laparoscopic surgery is discussed at the gynaecology
unsuitable then offer an open oncology multi-disciplinary meeting
surgery. following an MRI scan and tumour
markers.

Total hysterectomy with or without


bilateral salpingo-oopherectomy
should be performed once patient
does not need to preserve their
uterus.

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Aims and purpose
To guide general gynaecologists on the management of adult women with a
histological diagnosis of endometrial hyperplasia.

Background

Endometrial hyperplasia (EH) may be a precursor to endometrial cancer


therefore appropriate diagnosis and management is imperative.1
Incidence of EH is reported to be 3 times that of endometrial cancer, the
commonest gynaecological cancer.

About 1 in 41 women would be diagnosed with endometrial cancer in their
lifetime.2

EH is associated with multiple risk factors which are known to cause increased
and or unopposed oestrogen stimulation of endometrial cell growth. These risk
factors include:
Obesity
Oestrogen secreting ovarian tumours
Anovulation cycles in conditions such as PCOS (Polycystic Ovarian
Syndrome) and perimenopause.
Drugs such as Tamoxifen
Hormonal treatments such as oestrogen only HRT (Hormone
replacement therapy)

Immunosuppression and infection have been known to also cause EH.3

Diagnosis and clinical assessment


EH can only be diagnosed after histological examination of an endometrial
sample or polyp. This can be obtained via outpatient devices such as Pipelle
or inpatient procedures such as dilation and curettage

Outpatient devices like the Pipelle have been shown to be convenient and
have a high accuracy for diagnosing endometrial cancer, but modest accuracy
for diagnosing EH with a positive likelihood ratio of 12 and a negative
likelihood ratio of 0.2 4 Two percent of women may still have endometrial
hyperplasia despite a negative biopsy. A meta-analysis by Dijkhuizen et al
showed that Pipelle had a sensitivity of 81% in detecting EH in
postmenopausal women but over 99.6% sensitivity in detecting endometrial
carcinoma.5

It is recommended that women who present with persistent symptoms despite
previously negative or inconclusive Pipelle biopsy should have hysteroscopy
(outpatient or inpatient) to aid further endometrial sampling.1
Imaging (eg ultrasound scans) should not be used to diagnose EH, however,
they have a role in deciding whether biopsy of endometrium is indicated.

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Classification

Management of EH is based on the histological classification of an


endometrial sample. Currently, the 2014 World Health Organisation
classification 6 is recommended. This has simplified the histological diagnosis
into 2 categories:
Endometrial Hyperplasia without Atypia
Endometrial Hyperplasia with Atypia
Complex hyperplasia with mild atypia reflects pathological uncertainty about
the presence of atypia. The management of these cases should be considered
individually with a clinicopathological assessment and if necessary a
discussion with a member of the Gynae cancer MDT.

Management (see algorthym) comments

Consider laparoscopic surgery for hysterectomy. An MRI scan may be request


to aid surgical planning eg to assess uterine size.
Current studies show the risk of EH with atypia progressing to endometrial
cancer is 8% over 4 years without hysterectomy.7
When managing endometrial hyperplasia in a polyp or other discrete focal
lesion, the background endometrium should be sampled with the aid of a
hysteroscope if this was not undertaken during the polypectomy. Management
should be based on the histological classification of the background
endometrium as recommended in this guideline.

References

1. Royal College of Obstetricians and Gynaecologists. Green top guideline No. 67


Management of Endometrial Hyperplasia. RCOG/BSGE London. 2016.
https://www.rcog.org.uk/globalassets/documents/guidelines/green-
topguidelines/gtg_67_endometrial_hyperplasia.pdf
2. Cancer Research UK. Uterine cancer statistics. 2016.
http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-
by-cancer-type/uterine-cancer
3. Palmer et al. Review Endometrial Hyperplasia. The Obsterician and
Gynaecologist. 2008. 10; 211-16
4. Clark, T. J., Mann, C. H., Shah, N., Khan, K. S., Song, F. and Gupta, J. K.
(2001), Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial
hyperplasia. Acta Obstetricia et Gynecologica Scandinavica, 80: 784793
5. Dijkhuizen, F. P. H. L. J., Mol, B. W. J., Brlmann, H. A. M. and Heintz, A. P. M.
(2000), The accuracy of endometrial sampling in the diagnosis of patients with
endometrial carcinoma and hyperplasia. Cancer, 89: 17651772.
6. Kurman RJ, Carcangiu ML, Herrington CS, Young RH, editors. WHO
Classification of Tumours of Female Repro ductive Organs. 4th ed. [Lyon]: IARC;
2014.
7. Lacey JV, Sherman ME, Rush BB, et al. Absolute risk of endometrial carcinoma
during 20-year follow up among women with endometrial hyperplasia. J Clin
Oncol 2010; 28:788 - 92
Review date 8/4/2022
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