Endometrial Hyperplasia | Health and Life

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Endometrial Hyperplasia

Endometrial hyperplasia is defined as proliferation of endometrial glands, resulting in a greater gland-to-stroma ratio than normal endometrium. The disorder is characterized by variation in the size and shape of the proliferating glands and the potential for cytological atypia, which may progress to endometrial cancer. Endometrial hyperplasia usually results from chronic estrogen stimulation unopposed by progesterone.

Pathophysiology

Simple hyperplasia without atypia is least likely to progress to endometrial carcinoma, whereas complex hyperplasia with atypia is most likely to progress to carcinoma. The presence of nuclear atypia is the most worrisome finding. Progression to endometrial carcinoma was more than tenfold higher in women with atypical hyperplasia (simple or complex) than in women with no atypia (23 and 1.6 percent, respectively). Approximately 25 percent of women with atypical hyperplasia have coexistent endometrial cancer.

Risk factors for endometrial hyperplasia are the same as those for endometrial cancer. The risk for both disorders is increased tenfold in women who use unopposed estrogen-replacement therapy.

Risk factors for Endometrial Cancer

Increasing age
Unopposed estrogen ther-apy
Late menopause (after age 55)
Nulliparity
Polycystic ovary syndrome(chronic anovulation)
Obesity
Diabetes
Hereditary nonpolyposiscolorectal cancer
Tamoxifen
Early menarche
strogen secreting tumor
Family history of endometrial, ovarian, breast, or colon cancer

Etiology. Exposure of the endometrium to continuous estrogen unopposed by progesterone can lead to endometrial hyperplasia.

1. Endogenous estrogen. One source of endogenous unopposed estrogen is chronic anovulation is associated with polycystic ovary
syndrome (PCOS) and the perimenopausal period. Secretion of excessive estradiol from an ovarian tumor (eg, granulosa cell tumor) may also result in endometrial hyperplasia.

2. Exogenous estrogen. Continuous exposure to unopposed estrogen results in endometrial hyperplasia.

Clinical manifestations.

Endometrial hyperplasia should be suspected in women with heavy, prolonged, frequent, or irregular uterine bleeding. Abnormal uterine bleeding in perimenopausal or menopausal women is the most common clinical symptom of endometrial neoplasia, although such bleeding is usually (80 percent) due to a benign condition.

Screening

Diagnostic evaluation. Tissue is required for diagnosis of endometrial hyperplasia. Ultrasonography may be useful for selecting patients who should be biopsied.

Endometrial biopsy

1. An endometrial biopsy should be performed in all women with abnormal uterine bleeding in whom endometrial hyperplasia or carcinoma is a possibility. There is an excellent correlation between Novak or Pipelle biopsy instruments and curettage.

2. In addition, atypical glandular cells on a Papanicolaou (Pap) smear should be investigated with an endometrial biopsy to determine whether endometrial hyperplasia or carcinoma is the cause.

3. Endometrial biopsy is also recommended for women with any endometrial cells on a Papanicolaou (Pap) smear.

4. Additional endometrial assessment should be performed if abnormal uterine bleeding persists after a benign endometrial biopsy. Transvaginal sonography with or without hysteroscopy and directed biopsy should be considered to rule out an occult malignancy.

Hysteroscopy and curettage

If endometrial hyperplasia with atypia is diagnosed by blind biopsy, further evaluation is needed to exclude a coexistent endometrial adenocarcinoma, which is present in 25 percent. Hysteroscopy with curettage is recommended.

Transvaginal ultrasonography of women not on estrogen replacement therapy

1. Transvaginal ultrasonography (TVUS) has been used to select postmenopausal women with abnormal uterine bleeding not on estrogenreplacement therapy (ERT) who are at highest risk of having endometrial hyperplasia/cancer.

2. Endometrial biopsy is required for histological diagnosis if the stripe is >4 mm and in women with persistent bleeding. Persistent bleeding is worrisome even when the endometrial thickness is <4 mm, particularly if there are other risk factors for endometrial cancer.

Transvaginal ultrasonography in women on ERT.

TVUS is not a useful screening tool for excluding endometrial hyperplasia/cancer in women on estrogen-replacement therapy that is given with cyclic progesterone.

Women Who Should Undergo Evaluation for Endometrial Hyperplasia or Endometrial Cancer

Over age 40 years with abnormal uterine bleeding
Under age 40 years with abnormal uterine bleeding and risk factors (eg, chronic anovulation, obesity, tamoxifen)
Failure to respond to medical treatment of abnormal uterine bleeding
Postmenopausal women with uterus in situ receiv-ing unopposed estrogen replacement therapy
Presence of atypical glandular cells on Papanicolaou smear
Presence of endometrial cells on Papanicolaousmear in a woman >40 year of age
Women with hereditary nonpolyposis colorectal cancer

Treatment

Premenopausal women

1. No atypia.

Endometrial hyperplasia without atypia is treated with medroxyprogesterone acetate (MPA) 10 mg daily for 12 to 14 days each month for three to six months.

2. With atypia.

Endometrial hyperplasia with atypia on endometrial biopsy is further evaluated by hysteroscopy with dilatation and curettage.If the diagnosis remains unchanged (eg,no coexistent adenocarcinoma), treatment with continuous oral megestrol 40 mg two to four times per day is initiated. Hysterectomy is an alternative for women who are not planning future pregnancy.

Options for Progestin Treatment for Prevention of Endometrial Hyperplasia

Oral contraceptive pills
Levonorgestrel-releasing intrauterine device
Depot medroxyprogesterone acetate (150 mg IM)every three months
Intermittent progestin therapy taken daily for 12-14 days per month:
medroxyprogesterone acetate
norethindrone acetate
micronized progesterone in a vaginal cream

Continuous combined estrogen replacement therapy

Insertion of a levonorgestrel containing intrauterinedevice

Postmenopausal women

Endometrial hyperplasia without atypia is evaluated initially by hysteroscopy and dilatation and curettage. If the diagnosis remains unchanged and an ovarian estrogen source is excluded, then treatment with continuous medroxyprogesterone acetate (MPA,Provera) 10 mg daily for three months can be initiated. A follow-up endometrial biopsy should be performed immediately after cessation of drug therapy.

With atypia.

Endometrial hyperplasia with atypia is a premalignant condition, preferably treated with hysterectomy. Alternatively, continuous oral megestrol at doses of 40 mg two to four times per day can be administered after coexistent endometrial cancer is excluded. An endometrial biopsy should be performed after three months of therapy.

2011-08-03