This topic provides information about cancer of the lining of the uterus (endometrium). This topic focuses on type I endometrial cancer, which is the most common kind.
If you are looking for information about cancer of the cervix, see the topic Cervical Cancer.
What is endometrial cancer?
Endometrial cancer is the growth of abnormal cells in the lining of the uterus. The lining is called the endometrium. Endometrial cancer is also called cancer of the uterus, or uterine cancer.
Endometrial cancer usually occurs in women older than 50. The good news is that it is usually cured when it is found early. And most of the time, the cancer is found in its earliest stage, before it has spread outside the uterus.
What causes endometrial cancer?
The most common cause of endometrial cancer is having too much of the hormone estrogen compared to the hormone progesterone in the body. This hormone imbalance causes the lining of the uterus to get thicker and thicker. If the lining builds up and stays that way, then cancer cells can start to grow.
Women who have this hormone imbalance over time may be more likely to get endometrial cancer after age 50. This hormone imbalance can happen if a woman:
What are the symptoms?
The most common symptom of endometrial cancer is unexpected (abnormal) bleeding from the vagina after menopause. (If you are taking hormone therapy, some vaginal bleeding is expected.) About 20 out of 100 women who have abnormal bleeding after menopause have endometrial cancer.1 That means that 80 out of 100 women with abnormal bleeding don’t have this cancer.
A woman with advanced endometrial cancer may have other symptoms, such as losing weight without trying.
How is endometrial cancer diagnosed?
Endometrial cancer is usually diagnosed with a biopsy. In this test, the doctor removes a small sample of the lining of the uterus to look for cancer cells.
How is it treated?
Endometrial cancer in its early stages can be cured. The main treatment is surgery to remove the uterus plus the cervix, ovaries, and fallopian tubes. If the cancer has spread, the doctor may also remove the pelvic lymph nodes.
A woman whose cancer has spread may also have:
It’s common to feel scared, sad, or angry after finding out that you have endometrial cancer. Talking to others who have had the disease may help you feel better. Ask your doctor about support groups in your area. You can also find people online who will share their experiences with you.

Endometrial cancer is the fourth most common cancer in women, accounting for approximately 6,000 deaths per year in the United States. It is more common in women who are older, white, affluent, obese and of low parity. Hypertension and diabetes mellitus are also predisposing factors. Because any condition that increases exposure to unopposed estrogen increases the risk of endometrial cancer, tamoxifen therapy, estrogen replacement therapy without progestin and the presence of estrogen-secreting tumors are all risk factors. Smoking and the use of oral contraceptives appear to decrease the risk. Women with an increased risk and those with postmenopausal bleeding should be screened for endometrial cancer. Endometrial sampling is currently the most accurate and widely used screening technique, but ultrasonographic measurement of endometrial thickness and hysteroscopy have also been studied. Patients with endometrial specimens that show atypia have about a 25 percent likelihood of progressing to carcinoma, compared with less than 2 percent in patients without atypia. Endometrial cancer is usually treated surgically, but in patients with appropriate pathologic findings who decline surgical treatment, progestin therapy may be satisfactory.
Uterine cancer, the most common malignant neoplasm of the female genital tract and the fourth most common cancer in women, is currently diagnosed in about 34,000 women each year. In 1997, about 6,000 women in the United States died of this disease.1 It is more frequent in affluent and white women, especially obese, postmenopausal women of low parity.2 Hypertension and diabetes mellitus are also predisposing factors.3 Uterine cancer is most frequently diagnosed in industrialized western nations, with the lowest rates occurring in India and Southeast Asia.2
Advances in the past two decades have expanded our knowledge of endometrial cancer, giving us a better definition of the histologic subtypes and providing us with better screening and surgical tools with which to diagnose and treat this disease.2
Pathogenesis
It was originally hypothesized that endometrial hyperplasia represented a morphologic continuum from benign cystic hyperplasia to atypical complex hyperplasia, which may be the immediate precursor of endometrial carcinoma.2 Several recent studies have suggested that endometrial hyperplasia and endometrial cancer are two different entities, and the distinguishing feature is the presence or absence of cytologic atypia.2 Studies have shown that patients who have endometrial hyperplasia without atypia respond well to progestin therapy and are not at increased risk for cancer; however, patients with cytologic atypia show only a 50 percent response to progestin therapy, and cancer develops in 25 percent of cases.4-6
Uterine cancer is a general term used to describe many different histopathologic types of tumors found in the uterus. The most common cancer of the uterus is adenocarcinoma. Several other histologic subtypes also occur (Table 1). The less common forms are associated with a lower overall survival rate and a higher risk of metastatic disease at the time of surgical staging.2 Patients with serous (also known as papillary serous) and clear cell carcinomas tend to be older than those with other types (mean age: 66 versus 59 years) and are more likely to have abnormal cervical cytology.7 Serous carcinoma invades the myometrium and lymph-vascular spaces early and has been shown to metastasize without deep myometrial invasion.2
Risk Factors
Any characteristic that increases exposure to unopposed estrogen increases the risk for endometrial cancer (Table 2).2,4-8 Conversely, decreasing exposure to estrogen limits the risk. Unopposed estrogen therapy, obesity, anovulatory cycles and estrogen-secreting neoplasms all increase the amount of unopposed estrogen and thereby increase the risk for endometrial cancer. Smoking seems to decrease estrogen exposure, thereby decreasing the cancer risk, and oral contraceptive use increases progestin levels, thus providing protection.9 Tamoxifen (Nolvadex) therapy, often used in women with breast cancer, has an estrogenic effect on the female genital tract and, through this unopposed estrogen exposure, increases the risk for endometrial cancer.10 Physicians should be aware that endometrial ablation is not a treatment for endometrial hyperplasia or carcinoma, and a previous ablation does not protect against the development of endometrial disease.
Hormone Replacement Therapy
Unopposed estrogen treatment of menopause is associated with an eightfold increased incidence of endometrial cancer.11,12 The addition of progestin decreases this risk dramatically.12 For maximum endometrial protection, administration of medroxyprogesterone acetate (Provera), in a dosage of 10 mg daily, or norethindrone acetate (Aygestin), in a dosage of 2.5 mg daily, for a minimum of 12 to 14 days per month has been recommended.13 However, some physicians prescribe lower dosages, either 5.0 or 2.5 mg of medroxyprogesterone daily.
A 13-day “progestin challenge” course of either 10 mg of medroxyprogesterone or 2.5 to 5 mg of norethindrone given to postmenopausal women resulted in withdrawal bleeding and correlated with a high likelihood of endometrial pathology.13 In this study, it was found that low dosages may not provide maximal endometrial protection.13 However, the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial14 found no difference in the risk for endometrial disease between patients taking placebo and those taking estrogen with medroxyprogesterone, in a dosage of either 10 mg per day for 12 days or 2.5 mg per day continuously.
One possible explanation for these contradictions can be found in the patient groups studied. Many of the patients in one study had one or more risk factors for endometrial disease,13 whereas the PEPI trial involved a randomly selected cohort.14 These findings suggest that patients at high risk for endometrial disease should receive higher dosages of progestins than patients at low risk, a suggestion that is supported, in theory, by the pathophysiology. Further studies may be necessary for more definitive recommendations

Treatment
After diagnosis and initial evaluation, the doctor considers treatment options that fit each woman’s needs and discusses these options with her. The choice of treatment depends on the size of the tumor, the stage of the disease, whether female hormones affect tumor growth, and tumor grade. (The tumor grade tells how closely the cancer resembles normal cells and suggests how fast the cancer is likely to grow. Low-grade cancers are likely to grow and spread more slowly than high-grade cancers.) Other factors, including the woman’s age and general health, are also considered when planning treatment. Women with uterine cancer may be treated by a team of specialists that may include a gynecologist, gynecologic oncologist (a doctor who specializes in treating cancer of the female reproductive tract), and a radiation oncologist.
Getting a Second Opinion
Before starting treatment, a woman may want a second specialist to confirm the diagnosis and review her treatment options. It may take a week or two to arrange for another opinion, but a short delay will not reduce the chance that treatment will be successful. Some insurance companies require a second opinion; many others cover a second opinion if the patient requests it. There are a number of ways to find a doctor who can give a second opinion:
• The woman’s doctor may be able to suggest specialists to consult.
• The Cancer Information Service, at 1-800-4-CANCER, can tell callers about treatment facilities, including cancer centers and other programs supported by the National Cancer Institute.
• A woman can get the names of doctors from her local medical society, a nearby hospital, or a medical school.
• The Official ABMS Directory of Board Certified Medical Specialists lists doctors’ names along with their specialty and their background. This resource is in most public libraries.

Endometrial cancer - carcinoma of the lining of the uterus - is the most common gynecologic malignancy in women.
Description of Uterine Cancer
Endometrial carcinomas arise from the glands of the lining of the uterus, the pear-shaped organ in the pelvis. Cervical cancer and ovarian cancer are other types of gynecologic cancers in women.
Adenocarcinoma accounts for about 75 percent of all endometrial carcinomas. It occurs most often in women 50 to 70 years of age.
Endometrial adenocarcinomas that contain benign squamous cells are known as adenoacanthomas and account for about 17 percent of endometrial cancer.
The remaining three types of endometrial carcinoma have a poor prognosis. Approximately 15 percent of woman have adenosquamous carcinoma, in which both the gland cells and squamous cells are malignant.
Three percent have a clear cell carcinoma, and about one percent have a papillary carcinoma. Uterine sarcoma is another kind of uterine malignancy.
From where it arises in the lining of the uterus, untreated endometrial carcinoma eventually invades the wall of the uterus and may involve the cervix. With time, it can grow through the wall of the uterus into the surrounding tissues (the parametrium), the bladder and the rectum.
It also can spread by the lymphatic system to the vagina, fallopian tubes, ovaries, the pelvic and aortic lymph nodes and to the lymph nodes in the groin and above the collarbone (supraclavicular).

Introduction
The uterus (womb) is part of the female reproductive system and is located at the top of the vagina. It is where a baby grows during pregnancy.
The lining of the uterus is called the endometrium and is shed each month as part of your period. Most cancers of the uterus develop in the lining are called endometrial cancer. Cancer of the uterus can also be called uterine cancer.
Endometrial cancer is fairly common; about 5,000 - 6,000 women a year are affected (1). It mostly affects women between the ages of 50 and 70, who have been through the menopause (when your periods stop). It is more common in women who have never been pregnant. Like all cancers, it is important to get early treatment so that the cancer does not spread to other parts of the body.
About 95% of endometrial cancers of the uterus are adenocarcinomas. Cancers that start in the muscle of the womb (sarcomas) are even less common. There are three types of adenocarcinomas. The most common (over 75% of cases) is endometriod adenocarcinoma. The other types are papillary serous carcimona (5%), clear cell carcinoma (very rare), and leiomyosarcoma (rare).
The neck of the uterus is called the cervix. You can find more information about cancer of the cervix (cervical cancer) in the separate topic.

Cancer of the endometrium, or lining of the uterus (sometimes called the womb), is called endometrial cancer. The most common sign of endometrial cancer is unusual bleeding from your vagina, especially bleeding after menopause.

Endometrial cancer can almost always be treated successfully if it’s caught early. You can increase the chances that endometrial cancer will be found early by telling your doctor about any unusual bleeding.
Am I at risk for endometrial cancer?
Certain things may put you at greater risk for getting endometrial cancer. One risk factor is age. Endometrial cancer is most common in women who are over 50 years of age.

You may also be at greater risk if you have had high levels of estrogen in your body. Many things can increase your estrogen level. These include being extremely overweight, having high blood pressure or having diabetes.

Using estrogen replacement therapy without taking progestin may also increase the risk for endometrial cancer. For this reason, women who use hormone replacement therapy (HRT) generally take a combination of estrogen and the hormone progestin. Progestin seems to protect the lining of the uterus from the estrogen. In fact, using birth control pills that contain both estrogen and progestin during the childbearing years seems to decrease a woman’s risk of endometrial cancer.

Other things that may put you at greater risk for endometrial cancer include having your first period before the age of 12 or going through menopause after the age of 50. Women who have never been pregnant and women who use a medicine called tamoxifen may also be at greater risk.

How is endometrial cancer diagnosed?
Your doctor will diagnose endometrial cancer by performing one or more of the following procedures:
• Endometrial biopsy is usually done in your doctor’s office. It involves inserting a narrow tube into the uterus through the vagina and removing a small amount of tissue from the uterine wall. This tissue is tested in a lab for cancerous or precancerous cells. The procedure usually takes just a few minutes.
• Dilatation and curettage (D & C) involves dilating (widening) the cervix (the opening of the uterus) and inserting an instrument to scrape or suction the uterine wall and collect tissue. D & C is also an outpatient procedure. It takes about an hour and usually requires general anesthesia (puts you in a sleep-like state).
• Imaging tests are used in patients with certain medical conditions such as severe high blood pressure, obesity, diabetes, or other types of cancer. These patients may not be able to safely have anesthesia. In these patients, imaging tests such as an MRI scan, CT scan, or ultrasound may help diagnose cancer of the uterus.
Your doctor will talk to you about which procedure is right for you.
What is the treatment for endometrial cancer?
Treatment usually involves removing the uterus, the fallopian tubes and the ovaries. You may also need to take progestin to balance out high levels of estrogen. Sometimes radiation therapy or chemotherapy is also needed. Treatment can be very effective, especially if the cancer is found early.

Cancer
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Endometrial cancers develop in the uterus, though most develop in the endometrial glands that line the inner wall of the uterine cavity rather than in the uterus’ muscular wall.
Although endometrial cancer usually occurs after menopause, it also may occur around the time that menopause begins. Abnormal vaginal bleeding is the most common symptom of uterine cancer. Bleeding may start as a watery, blood-streaked flow that gradually contains more blood. Women should not assume that abnormal vaginal bleeding is part of menopause.
You should see your doctor if you have any of the following symptoms:
• Unusual vaginal bleeding or discharge
• Difficult or painful urination
• Pain during intercourse
• Pain in the pelvic area

By far, the most common symptom of endometrial carcinoma is abnormal bleeding from the vagina.
In women who have been through menopause, any vaginal bleeding is abnormal and should be evaluated by a doctor.
In women who have not been through menopause or who are currently going through menopause, distinguishing normal menstrual bleeding from abnormal bleeding may be difficult. A heavier or more frequent period or bleeding between periods is sometimes linked to cancer in menstruating women. During the transient period of going through menopause, the menstrual period should become shorter and shorter and the frequency should become farther apart. Any other bleeding should be reported to a doctor.
The following symptoms are much less common and usually indicate fairly advanced cancer:
Pelvic pain
Mass (swelling or lump) in the pelvic area
Weight loss

A risk factor is anything that increases your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, mouth, throat, kidney, bladder, and several other organs.
There are different kinds of risk factors. Some, such as your age or race, can’t be changed. Others are related to personal choices such as smoking, drinking, or diet. Some factors influence risk more than others. But having a risk factor, or even several, does not necessarily mean that you will get the disease.
Most endometrial cancers, mainly Type 1, are said to be hormone-driven. That means that a woman’s hormone balance plays a part in their development. Female hormones are produced by the ovaries before menopause. The ovaries normally produce two main types of female hormones — estrogen and progesterone. The balance between these hormones changes during a woman’s menstrual cycle each month. This produces a woman’s monthly periods and keeps the endometrium healthy. A shift in the balance of these two hormones toward more estrogen increases a woman’s risk for developing endometrial cancer. After menopause, the source of estrogen is from fat (see below). Many of the known risk factors for endometrial cancer such as early onset of menstruation (menarche), late menopause, few pregnancies or infertility, and obesity relate to estrogen.
Risk factors for endometrial cancers include the following:
Total number of menstrual cycles: Having more menstrual cycles during a woman’s lifetime raises her risk of endometrial cancer. Starting menstrual periods (menarche) before age 12 and/or going through menopause later in life raises the risk. Starting periods early is less a risk factor for women with early menopause. Likewise, late menopause may not lead to a higher risk in women whose periods began later in their teens.
History of infertility (not being able to become pregnant) or never having given birth: During pregnancy, the hormonal balance shifts toward more progesterone. Therefore, having many pregnancies reduces endometrial cancer risk, and women who have not been pregnant have a higher risk.
Obesity (being very overweight): Although most of a woman’s estrogen is produced by her ovaries, fat tissue can change some other hormones into estrogens. Having more fat tissue can increase a woman’s estrogen levels and therefore increase her endometrial cancer risk. In comparison with women who maintain a healthy weight, endometrial cancer is twice as common in overweight women, and more than three times as common in obese women.
Tamoxifen: Tamoxifen is an anti-estrogen drug that is used to treat breast cancer. It is also used to reduce the risk of breast cancer in women who are at a high risk of developing it. Although it is called an anti-estrogen, it acts like an estrogen in the uterus. It can cause the uterine lining to grow, which increases the risk of endometrial cancer.
The relatively small risk of developing endometrial cancer (about one in 500) in women taking tamoxifen must be balanced against the value of this drug in treating breast cancer and reducing the likelihood of cancer in the other breast. This is an issue women may want to discuss with their doctors. If a woman decides to take tamoxifen, she should have yearly gynecologic exams and should be sure to report signs and symptoms of endometrial cancer such as abnormal bleeding.
Estrogen therapy (ET): ET uses estrogen to offset the symptoms of menopause. It once was common to prescribe estrogen alone (without progestins) to treat symptoms of menopause such as hot flashes and weakening of the bones (osteoporosis). Doctors have found, however, that the use of estrogen alone increases a woman’s risk for getting endometrial cancer by as much as five times. Studies now show that giving progesterone-like drugs along with estrogen will avoid this additional risk of endometrial cancer. This approach is called combined hormone therapy or HT.
Recent studies have shown that the combination of progesterone-like drugs and estrogens increase a woman’s chance of developing breast cancer and problems with blood clots. Therefore, it is important to discuss potential risks with your doctor if you use these medicines. If you choose to use them, you should use them at the lowest possible dose and for the shortest possible time. You should also have at least yearly follow-up checks for cancer. If you have any abnormal bleeding or discharge you should see your doctor or other health care provider right away.
Ovarian diseases: Certain ovarian tumors such as granulosa-theca cell tumors make estrogen. Women with polycystic ovarian syndrome (ovaries with many cysts) have estrogen levels that are higher than normal, along with lower levels of progesterone. In either of these conditions, the increase in estrogen relative to progesterone can increase a woman’s chance of getting endometrial cancer.
A diet high in animal fat: A high-fat diet can increase the risk of several cancers, including endometrial cancer. Because fatty foods are also high-calorie foods, a high fat diet can lead to obesity, which is a well-known endometrial cancer risk factor. Many scientists think this is the main way in which a high fat diet raises endometrial cancer risk. Some scientists think that fatty foods may also have a direct effect on estrogen metabolism, which increases endometrial cancer risk.
Diabetes: Endometrial cancer may be as much as four times more common in women with diabetes. Because diabetes is more common in people who are overweight, some doctors think it is being overweight that is the risk factor for endometrial cancer. However, some studies find that endometrial cancer risk is higher in women who are overweight and diabetic than in women who are overweight but not diabetic. Even women with type I diabetes (those who need insulin injections) have higher rates of endometrial cancer despite the fact that their diabetes is not caused by obesity.
Family history: Endometrial cancer tends to run in some families. Some of these families also have an inherited tendency to develop a type of colon cancer called hereditary nonpolyposis colon cancer (HNPCC). As many as half of women with this inherited disorder will get endometrial cancer. Women with colon cancer or endometrial cancer in several family members might want to think about having genetic counseling and testing. Genetic testing can help determine if you or members of your family have a high risk of getting endometrial cancer. If you do, a hysterectomy may be recommended once you are through having your children and endometrial sampling is recommended annually for women 35 years of age or older.
There are some families that have a high rate of only endometrial cancer. These families probably have a different genetic disorder than HNPCC. It hasn’t yet been determined what the genetic defect is.
Breast or ovarian cancer: Women who have had breast cancer or ovarian cancer may have an increased risk of developing endometrial cancer. Some of the dietary, hormonal, and reproductive risk factors for breast and ovarian cancer also increase endometrial cancer risk.
Prior pelvic radiation therapy: Radiation used to treat some other cancers can damage the DNA of cells, sometimes increasing the risk of a second type of cancer such as endometrial cancer.
Although these factors increase a woman’s risk for developing endometrial cancer, they do not always cause the disease. Many women with one or more of these risk factors never develop endometrial cancer. Some women with endometrial cancer do not have any of these risk factors. Even if a woman with endometrial cancer has one or more risk factors, there is no way to know which, if any, of these factors was responsible for her cancer.

This National Cancer Institute (NCI) booklet (NIH Publication No. 01-1562) has important information about cancer* of the uterus. In the United States, cancer of the uterus is the most common cancer of the female reproductive system. It accounts for six percent of all cancers in women in this country.
This booklet has information about the possible causes, symptoms, diagnosis, and treatment of cancer of the uterus. It will help patients and their families and friends better understand and cope with this disease.
Research is increasing what we know about cancer of the uterus. Scientists are learning more about its causes. They are exploring new ways to prevent, detect, diagnose, and treat this disease. Research has helped to improve patients’ quality of life and lower the chance of dying from this disease.
Information specialists at the Cancer Information Service can answer callers’ questions about cancer and can send other National Cancer Institute publications. The number to call is 1-800-4-CANCER. Also, anyone may view or order NCI publications on the Internet at http://www.cancer.gov/publications.