What Causes Endometrial Cancer?

In general, cancer begins when a genetic mutation (change in certain genes) turns normal healthy cells into abnormal cells. Healthy cells grow and multiply at a set rate and eventually die at a set time. Abnormal cells grow and multiply out of control, and they do not die. The abnormal cells clump together to create a mass (tumor). Cancer cells invade nearby tissues and can separate from an initial tumor to spread to other parts of the body (metastasize). Doctors do not know what causes the genetic mutation that triggers the development of endometrial cancer.

Scientists believe that levels of estrogen, a hormone, or chemical messenger, play a role in the development of endometrial cancer because women who are exposed to higher levels, either naturally or from outside sources, are more likely to develop endometrial cancer. Estrogen is the female sex hormone produced by the ovaries. It is responsible for the development of female sex characteristics, such as a uterus and breasts. Estrogen helps control a woman’s monthly periods and prepare her body for fertilization and reproduction.

Risk Factors for Endometrial Cancer

Doctors and researchers believe that certain factors, known as risk factors, increase a woman’s chances of getting endometrial cancer. However, not everyone with a risk factor will develop endometrial cancer and women without any risk factors can develop the disease.

Hormones are chemical substances formed in one part of the body that affect physiologic activity in another part of the body. Estrogen is the female sex hormone made by the ovaries. It is responsible for the development of female sex characteristics, such as a uterus and breasts. Estrogen helps control a woman’s monthly periods and prepare her body for fertilization and reproduction. When a balance of hormones in a woman’s body shifts toward increased levels of estrogen, this stimulates the growth of the endometrium and a woman’s risk of endometrial cancer increases.

Factors that are associated with an increase in the level of estrogen, and therefore with an increase in a woman’s risk of endometrial cancer, included:

Risk factors for endometrial cancer include:

• Age - Endometrial cancer is most common in women over age 50.
• Breast or ovarian cancer - Women who have had breast or ovarian cancer may have an increased risk of getting endometrial cancer.
• Diabetes - Endometrial cancer is up to four times more common in women with diabetes than women without this disease.
• Diet - High-fat diets can lead to obesity, which increases a woman’s risk of endometrial cancer. 
• Endometrial hyperplasia - Women who have endometrial hyperplasia, a noncancerous increase in the number of cells lining the uterus, have a higher risk of endometrial cancer.
• Hormone replacement therapy - Women who take estrogen without progesterone (a female hormone that is involved in women’s monthly cycles and pregnancies) to control the symptoms of menopause have a higher risk of endometrial cancer. Women who use a combination of estrogen and progesterone  have a lower risk of uterine cancer than women who take estrogen alone because the progesterone protects the uterus.
• Family history - Endometrial cancer runs in some families. For example, families with a disease known as Lynch syndrome have an increased risk of colon and endometrial cancer. Up to half of all women with this inherited disorder develop endometrial cancer.
• Infertility - Pregnancy appears to protect women from endometrial cancer. As a result, women who are unable to become pregnant or who have never given birth have a higher risk of endometrial cancer.
• Irregular ovulation - Estrogen regulates ovulation, the monthly release of an egg from an ovary. Irregular ovulation or failure to ovulate can increase a woman’s exposure to estrogen, which can increase her risk of endometrial cancer.
• Number of menstrual cycles - A higher number of menstrual cycles (monthly periods) during a woman’s lifetime increases her risk of endometrial cancer. Women who started their monthly periods before age 12 and/or went through menopause later in life also have a higher risk.
• Obesity - Women with more fat tissue sometimes have higher levels of estrogen, and this increases their risk of endometrial cancer. Endometrial cancer is twice as common in overweight women as normal-weight women.
• Ovarian diseases - Women with certain ovarian conditions, such as granulosa-theca cell tumors (tumors of the ovary that are not usually cancerous) and polycystic ovarian syndrome (a disease that causes enlarged ovaries and many small cysts, or pouches of air or fluid), have abnormally high levels of estrogen, which can increase their chance of endometrial cancer.
• Race - White women have a higher risk of endometrial cancer than African-American women.
• Radiation therapy - Radiation treatment to the pelvis (lower part of the abdomen between the hip bones) given for other cancers sometimes increases the risk of a second type of cancer, such as endometrial cancer.
• Tamoxifen therapy - Women who have taken tamoxifen, an antiestrogen drug used to treat breast cancer or reduce the risk of breast cancer in high-risk women, have an increased risk of endometrial cancer. The risk of developing endometrial cancer in women who take tamoxifen is relatively small, about 1 in 500.