Endometrial abnormalities Flashcards
What should the initial management of hyperplasia without atypia be?
Reversible risk factors such as obesity and the use of hormone replacement therapy (HRT) should be
identified and addressed if possible.
Observation alone with follow-up endometrial biopsies to ensure disease regression can be considered,
especially when identifiable risk factors can be reversed. However, women should be informed that
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 and in
symptomatic women with abnormal uterine bleeding.
What are the risks of hyperplasia without atypia?
The risk of endometrial hyperplasia without atypia progressing to endometrial cancer is less than 5% over 20 years and that the majority of cases of endometrial
hyperplasia without atypia will regress spontaneously during follow-up.
What should the first-line medical treatment of hyperplasia without atypia be?
Both continuous oral and local intrauterine (levonorgestrel-releasing intrauterine system [LNG-IUS])
progestogens are effective in achieving regression of endometrial hyperplasia without atypia.
The LNG-IUS should be the first-line medical treatment because compared with oral progestogens it
has a higher disease regression rate with a more favourable bleeding profile and it is associated with
fewer adverse effects.
Continuous progestogens should be used (medroxyprogesterone 10–20 mg/day or norethisterone
10–15 mg/day) for women who decline the LNG-IUS.
Cyclical progestogens should not be used because they are less effective in inducing regression of
endometrial hyperplasia without atypia compared with continuous oral progestogens orthe LNG-IUS.
What should the duration of treatment and follow-up of hyperplasia without atypia be?
Treatment with oral progestogens or the LNG-IUS should be for a minimum of 6 /12.
If fertility is not desired, women should be encouraged to retain the LNG-IUS for up to 5 years as this reduces the risk ofrelapse.
Endometrial surveillance is recommended at a minimum of 6-monthly intervals, although review
schedules should be individualised and responsive to changes in a woman’s clinical condition.
At least two consecutive 6-monthly negative biopsies should be obtained prior to discharge.
Women should be advised to seek a further referral 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 a body mass index (BMI) of 35 or greater or
those treated with oral progestogens, 6-monthly endometrial biopsies are recommended. Once two
consecutive negative endometrial biopsies have been obtained then long-term follow-up should be
considered with annual endometrial biopsies.
When is surgical management appropriate for women with endometrial hyperplasia without atypia?
Hysterectomy should not be considered as a first-line treatmentfor hyperplasia without atypia.
Hysterectomy is indicated in women not wanting to preserve their fertility when
(i) progression to atypical hyperplasia occurs during follow-up, or
(ii) there is no histological regression of hyperplasia
despite 12 months of treatment, or
(iii) there is relapse of endometrial hyperplasia after completing progestogen treatment, or
(iv) there is persistence of bleeding symptoms, or
(v) the woman declines to undergo endometrial surveillance or comply with medical treatment.
For endometrial hyperplasia without atypia who needs surgery what approach?
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 individualised; however,
bilateral salpingectomy should be considered as this may reduce the risk of a future ovarian
malignancy.
Endometrial ablation is not recommended for the treatment of endometrial hyperplasia because
complete and persistent endometrial destruction cannot be ensured and intrauterine adhesion
formation may preclude future endometrial histological surveillance.
How should atypical hyperplasia be managed?
Women with atypical hyperplasia should undergo a total hysterectomy because of the risk of underlying malignancy or progression to cancer.
For endometrial hyperplasia with atypia who needs surgery what approach?
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 individualised; however,
bilateral salpingectomy should be considered as this may reduce the risk of a future ovarian
malignancy
How should women with atypical hyperplasia who wish to preserve their fertility or who are not suitable for surgery be managed?
Women wishing to retain theirfertility should be counselled about the risks of underlying malignancy
and subsequent progression to endometrial cancer.
Pretreatment investigations should aim to 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.
First-line treatment with the LNG-IUS should be recommended, with oral progestogens as a
second-best alternative (see section 7.2).
Once fertility is no longer required, hysterectomy should be offered in view of the high risk of disease
relapse.
How should women with atypical hyperplasia not undergoing hysterectomy be followed up?
Routine endometrial surveillance should include endometrial biopsy. Review schedules should be
individualised 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.
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.
How should endometrial hyperplasia be managed in women wishing to conceive?
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.
Assisted reproduction may be considered as the live birth rate is higher and it may prevent relapse
compared with women who attempt natural conception.
Prior to assisted reproduction, regression of endometrial hyperplasia should be achieved as this is
associated with higher implantation and clinical pregnancy rates.
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
combinedHRT preparation. Subsequent management should be as described in the preceding sections
of the guideline.
Women with endometrial hyperplasia taking a continuous combined preparation who wish to continue
HRT should have their need to continueHRT reviewed. Discuss the limitations ofthe available evidence
regarding the optimal progestogen regimen in this context. Consider using the LNG-IUS as a source of
progestogen replacement. Subsequent management should be as described in the preceding sections
of the guideline.
How should endometrial hyperplasia be managed in women on adjuvant treatment for breast cancer?
Women taking tamoxifen should be informed about the increased risks of developing endometrial
hyperplasia and cancer. They should be encouraged to report any abnormal vaginal bleeding or
discharge promptly.
Women taking aromatase inhibitors (such as anastrozole, exemestane and letrozole) should be
informed that these medications are not known to increase the risk of endometrial hyperplasia and
cancer.
Should women on tamoxifen be treated with prophylactic progestogen therapy?
There is evidence that the LNG-IUS prevents polyp formation and that it reduces the incidence of
endometrial hyperplasia in women on tamoxifen. The effect ofthe LNG-IUS on breast cancerrecurrence
risk remains uncertain so its routine use cannot be recommended.
How should women who develop endometrial hyperplasia while on tamoxifen treatment for breast
cancer be managed?
There is evidence that the LNG-IUS prevents polyp formation and that it reduces the incidence of
endometrial hyperplasia in women on tamoxifen. The effect ofthe LNG-IUS on breast cancerrecurrence
risk remains uncertain so its routine use cannot be recommended.
How should women who develop endometrial hyperplasia while on tamoxifen treatment for breast
cancer be managed?
The need fortamoxifen 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 endometrial hyperplasia confined to an endometrial polyp be managed?
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
What is tamoxifen used for
Endocrine treatment of choice for selected patients with breast cancer
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Preventative role in healthy women at increased risk of developing breast cancer.
How does it work ?
Estrogen receptor modulator
Inhibits proliferation of breast cancer by competitive antagonism at the estrogen receptor
It is a partial agonist on other tissues including the vagina and uterus
Tamoxifen SEs on the female genital tract:
- Stimulation of endometriosis, with worsening of symptoms in some patients. There has been one case report of an endometrioid carcinoma arising from an ovarian endometriotic focus.
- Stimulation of the growth of benign fibroids.
- An increased incidence of benign endometrial polyps, proliferation and hyperplasia.
• Population based data suggest an apparent small increase in the risk of uterine sarcoma with Tamoxifen use.
What is the risk of endometrial cancer in woman taking tamoxifen ?
- The cumulative risk of endometrial cancer with Tamoxifen use is 1.6% at five years and 3.1% if used for 5-14 yrs.
- The risk of developing endometrial cancer in patients on Tamoxifen prophylaxis is only observed in post-menopausal women (RR = 4.01). (NOT premenopausal woman)
- Patients that have an endometrial lesion detected prior to commencing Tamoxifen have a statistically significant higher risk of developing atypical lesions at two years compared to patients that did not have a pre-existing endometrial lesion.
- The stage and grade of uterine endometrioid adenocarcinoma found in women on standard doses of Tamoxifen is comparable to those tumours found in women not taking Tamoxifen.
What is the effect of the mirena on the endometrium?
A 2009 Cochrane review found that the LNG-IUS reduced the incidence of new endometrial polyps in women on tamoxifen for breast cancer over a 1-year period (Peto OR 0.14, 95% CI 0.03–0.61).
There was no clear evidence that the LNG-IUS prevented endometrial hyperplasia or cancer in these women.
An updated subgroup analysis has confirmed that endometrial hyperplasia is reduced as well as endometrial polyp formation
Lymph drainage of the uterine corpus
The lymphatic system of the corpus uteri is formed by three main lymphatic trunks: utero‐ovarian (infundibulopelvic), parametrial, and presacral.
These drain into the
They collectively drain into the hypogastric (also known as internal iliac), external iliac, common iliac, presacral, and para‐aortic nodes.
Where does endometrial ca metastasis to?
The vagina, ovaries, and lungs are the most common metastatic sites.
