Endometrial hyperplasia-includes simple and complex forms.
Excessive proliferation of the cells of the endometrium.
Most cases related to elevated levels of estrogens combined with
insufficient levels of progesterone, which counteracts estrogen’s prolferative influence on the endomtrium.
Also termed endometrial intraepithelial neoplasia
Simple hyperplasia without cellular atypia appears closest to normal proliferative endometrium.
Complex atypical hyperplasia resembles well differentiated endometroid adenocarcinoma.
Complex atypical hyperplasia share microsatellite instability and PTEN, CTNNB1 and k-ras mutations with well differentiated adenocarcinoma of the uterus.
Complex atypical hyperplasia associated with a significant risk for coincident adenocarcinoma.
Treated with hysterectomy without lymph node dissection.
Approximately 39% of hysterectomies for complex atypical hyperplasia contain adenocarcinoma and 33% indicate myometrial invasion.
May be associated with polycystic ovary syndrome, estrogen producing tumors and estrogen replacement therapy.
Prevention and treatment of endometrial hyperplasia
A condition in which the uterine lining is thicker than normal.
Its most important association is with endometrial malignancy.
It is mandatory to distinguish between different types of EH, namely, those which are benign and those which are precancerous.
The most useful systems of classification based on microscopic appearances categorize EH as:
EH benign without atypia
Endometrioid neoplasia, endometrial intraepithelial neoplasia
EH benign without atypia is a response to abnormal estrogen stimulation of the endometrium, and regresses once the exposure ceases and adequate progesterone exposure is initiated.
The cells are normal in appearance and there are no mutations associated with malignancy
Endometrioid neoplasia, endometrial intraepithelial neoplasia is premalignant, with genetic changes linked to malignant transformation, and is associated strongly with coexistent endometrioid cancer in 36% of cases or a high risk of developing it within a few years.
Treatment depends on the etiology and direction of the lesion.
What is the histopathologic diagnosis?
Whether the woman wants to conceive again.
Whether she is exposed to estrogens currently.
Severity of symptoms.
In most cases, benign EH is treated conservatively,with removing sources of estrogen, whether exogenous or endogenous.
Risk factors for benign EH include:
Sedentary lifestyle with lack of exercise.
Obesity with peripheral fatty tissue containing the enzyme aromatase convert androgens to estrogens, promoting endometrial thickening.
Unhealthy diet which promotes weight gain.
Use of estrogen hormone replacement therapy (HRT) in postmenopausal women, or other estrogen delivery systems, which should be replaced with combined cyclic or continuous HRT.
Approximately 1% of patients who are on combined hormonal replacement therapy develop benign endometrial hyperplasia.
In endometrial hyperplasia from combined hormonal therapy doses should be increased or switching to 3 months of progestin-only therapy to encourage the regression of hyperplastic endometrium.
In most cases, benign EH may be treated with progesterone using Medroxy progesterone acetate (MPA) 10 mg by mouth daily, mor icronized progesterone 300 mg by mouth daily in 14-day regimens,
Each 14-day cycle is followed by cyclic bleeding and the endometrium is reassessed by a biopsy after 3 or 4 months of treatment.
Progestins inhibit cell division in the endometrium within 11 days of initiation of treatment, and reverse the proliferative changes of EH.
Progesterone effects on the endometrium include atrophy of the glandular epithelium, increased eosinophilic staining of the cytoplasm and changes in the stromal fluid retention, and its response is determined mostly by the progestin receptor status of the abnormal endometrium.
Patients showing complete regression of EH should continue therapy.
The use of combined estrogen plus progesterone hormone replacement therapy if patient is postmenopausal, either in cyclic or combined form.
If only a partial regression occurs, the doses of progesterone are increased and the 14-day regimen continued using:
MPA 10 mg by mouth four times daily
Megestrol acetate 80 mg daily by mouth.
After 3 months the endometrium is reassessed by biopsy.
If there is no response, or patients show breakthrough bleeding, the treatment of choice is a total hysterectomy.
Endometrial intraepithelial neoplasia in premenopausal patients, is treated with high doses of progestational agents:
MPA 100 mg by mouth daily
Megestrol acetate 160 mg daily by mouth
MPA injections 1 g intramuscularly per week for 12 weeks
Levonorgestrel intrauterine device, which avoids systemic and gastric side-effects which releases 20 μg/day, and is left in place for a period of 6 months to 2 years in this condition
Postmenopausal women with endometrial intraepithelial neoplasia should undergo total hysterectomy because of the high risk of endometrial cancer, and because 80% will not respond to progestins.
In 25-90% of premenopausal women with endometrial intraepithelial neoplasia, it is reversed to a secretory type of endometrium.
The outcome using an levonorgestrel intrauterine device-IUS is generally better with endometrial hyperplasia, up to 100%, compared to 67-88% with endometrial intraepithelial neoplasia, it is reversed to a secretory type of endometrium.
In patients with benign endometrial hyperplasia who do not respond to progestins by cessation of abnormal bleeding, a total hysterectomy is recommended.
Minimally invasive surgical techniques in endometrial hyperplasia include:
Ablative methods such as cryosurgery, laser ablation and electrocoagulation, which uses liquid nitrogen or other freezing gases, laser energy or heat to remove the endometrium respectively.
With hystero-resection the whole of the endometrium is resected, including the basal layer, under direct hysteroscopic guidance.
Hystero-resection is the preferred method when available as it provides tissue for microscopic examination, ensures good control of bleeding and provides control over the depth of tissue removed
Hystero-resection is not indicated:
Tamoxifen use with repeated bleeding
Obesity, diabetes mellitus and postmenopausal status which are all risk factors for endometrial cancer