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Excess Uterine Bleeding & Hormone Therapy

What is endometrial hyperplasia?

Endometrial hyperplasia occurs when the endometrium, the lining of the uterus, becomes too thick. It is not cancer, but in some cases, it can lead to cancer of the uterus. Thus  the main concerns is the potential malignant transformation of the endometrial hyperplasia to the endometrial cancer.

 

How does the endometrium normally change throughout the menstrual cycle?

The endometrium changes throughout the menstrual cycle in response to hormones. During the first part of the cycle, the hormone estrogen is made by the ovaries. Estrogen causes the lining to grow and thicken to prepare the uterus for pregnancy. In the middle of the cycle, an egg is released from one of the ovaries (ovulation). Following ovulation, levels of another hormone called progesterone begin to increase. Progesterone prepares the endometrium to receive and nourish a fertilized egg. If pregnancy does not occur, estrogen and progesterone levels decrease. The decrease in progesterone triggers menstruation, or shedding of the lining. Once the lining is completely shed, a new menstrual cycle begins.

What causes endometrial hyperplasia?

Endometrial hyperplasia most often is caused by continuous excess estrogen without progesterone exposure as happen in women who do not form egg. If ovulation does not occur, progesterone is not made, and the lining is not shed. The endometrium may continue to grow in response to estrogen. The cells that make up the lining may crowd together and may become abnormal. This condition, called hyperplasia, may lead to cancer in some women. Hyperplasia often spontaneously reverts to normal, particularly if it occurs at a low level during the hormone changes associated with perimenopause (the beginning of menopause). If it does not revert to normal, hyperplasia may progress through a series of stages.

Premenopausal hyperplasia often reverts to normal in the early, simple, or cystic stages. When it does not revert to normal, the endometrium may continue to thicken and develop into adenomatous, complex hyperplasia with atypia. If untreated it may develop into endometrial cancer.

When does endometrial hyperplasia occur?

Endometrial hyperplasia usually occurs after menopause, when ovulation stops and progesterone is no longer made. It also can occur during perimenopause, when ovulation may not occur regularly. Listed as follows are other situations in which women may have high levels of estrogen and not enough progesterone:

·         Use of medications that act like estrogen

·         Long-term use of high doses of estrogen after menopause (in women who have not had a hysterectomy)

·         Irregular menstrual periods, especially associated with polycystic ovary syndrome or infertility

·         Obesity

 

What risk factors are associated with endometrial hyperplasia?

Endometrial hyperplasia is more likely to occur in women with the following risk factors:

·         Age older than 35 years

·         White race

·         Never having been pregnant

·         Older age at menopause

·         Early age when menstruation started

·         Personal history of certain conditions, such as diabetes mellitus, polycystic ovary syndrome, gallbladder disease, or thyroid disease

·         Obesity

·         Cigarette smoking

·         Family history of ovarian, colon, or uterine cancer

 

What are signs and symptoms of endometrial hyperplasia?

The most common sign of hyperplasia is abnormal uterine bleeding. If you have any of the following, you should see your health care provider:

·         Bleeding during the menstrual period that is heavier or lasts longer than usual

·         Menstrual cycles that are shorter than 21 days (counting from the first day of the menstrual period to the first day of the next menstrual period)

·         Any bleeding after menopause

 

How is endometrial hyperplasia diagnosed?

There are many causes of abnormal uterine bleeding. If you have abnormal bleeding and you are 35 years or older, or if you are younger than 35 years and your abnormal bleeding has not been helped by medication, your health care provider may perform diagnostic tests for endometrial hyperplasia and cancer.

Ultrasound
Imaging the endometrium on days 5-10 of a woman's cycle reduces the variability in endometrial thickness.

·         premenopausal

o    normal endometrial thickness depends on the stage of the menstrual cycle, but a thickness of >15 mm is considered top normal in the secretory phase

o    hyperplasia can be reliably excluded in patients only when the endometrium measures less than 6 mm 1

·         postmenopausal

o    a thickness of >5 mm is considered abnormal

The appearance can be non-specific and cannot reliably allow differentiation between hyperplasia and carcinoma 5. Usually, there is a homogeneous increase in endometrial thickness, but endometrial hyperplasia may also cause asymmetric/focal thickening with surface irregularity, an appearance that is suspicious for carcinoma.

Up to one-third of endometrial cancers to be preceded by hyperplasia. A biopsy is required for a definitive diagnosis.

Because endometrial hyperplasia has a non-specific appearance, any focal abnormality should lead to biopsy if there is clinical suspicion for malignancy (e.g. vaginal bleeding).

The first step in determining if you have hyperplasia is a pelvic and transvaginal ultrasound, which evaluates the thickness of the endometrium. The endometrium is thickest right before menstruation begins and thinnest right after it ends. So if an ultrasound is performed it should be completed within a day or two after menstruation stops-- when the thickness of the endometrium is usually between 4mm and 7mm.

If a pelvic and transvaginal ultrasound reveals that the endometrium is abnormally thickened, it should be confirmed the following month with a repeat ultrasound. The repeat ultrasound should also be performed within a day or two after menstruation stops.

If the endometrium remains thickened or if bleeding is continuous for two months in a row, then a D&C will both diagnose and treat hyperplasia. D&C refers to dilation, opening the cervical canal, and curettage, scraping the endometrium with a sharp instrument called a curette. A gynecologist inserts a curette through the dilated cervix and into the uterus. The doctor will then scrape the endometrium and send the tissue to a pathologist for analysis and diagnosis. The D&C allows a pathologist to determine if hyperplasia exists. If hyperplasia is present, the D&C will help determine what level of hyperplasia was found and determine if further treatment is indicated. There are several stages of endometrial hyperplasia, starting with simple, then cystic, and on up the ladder until the last stage, complex hyperplasia with significant atypia that is poorly differentiated. The diagnosis can be made by a pathologist after a D&C.

TREATMENT OF ENDOMETRIAL HYPERPLASIA

An early level of hyperplasia usually responds to a small dosage of progesterone, such as Provera. A higher level of hyperplasia responds better to a stronger progesterone, such as Megace. With a higher level of hyperplasia, after three months of treatment with a high dose of Megace, a D&C should be repeated to make sure the tissue is returning to normal. Once the endometrium returns to normal, an ultrasound every six to eight months will show whether the endometrium is thick, and if a D&C is warranted.

Early endometrial cancer may respond to a high dose of Megace as well. More frequent monitoring with ultrasound and a D&C every six months for the first 12 to 18 months is important to monitor the endometrial thickness.

Thus treatment can be provided as

1.     High dose of cyclic Progesterone

2.     Mifepristone

3.     Ormeloxifene

With theses treatment endometrial hyperplasia can be cured in most and uterus removal can be avoided

 Other tests may be needed as endometrial biopsydilation and curettage, or hysteroscopy.

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