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The information on this page was reviewed and approved by
Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was updated on July 8, 2021.

Risk factors for uterine cancer

Each year, more than 60,000 women are diagnosed with endometrial cancer or uterine sarcoma, the two primary types of uterine cancer. No one knows if or when uterine cancer will develop, so it is important to understand the risk factors of the disease.

What causes uterine cancer?

Uterine cancer forms when the DNA in cells in the uterus mutate, disabling functions that control cell division and growth. In most cases, cancer cells in the uterus are found in the endometrium, the inner lining of the uterus. This is called endometrial cancer. While the exact cause of a woman’s uterine cancer may not be known, certain risk factors are strongly linked to the disease, including obesity and high blood sugar.

Uterine sarcoma and endometrial cancer have different risk factors. Having one risk factor for cancers of the uterus, or even several, doesn’t mean you will get the disease. Likewise, having no common risk factors doesn’t mean you will not develop cancer.

Known risk factors for uterine cancer include:

General

Age: Most women diagnosed with endometrial cancer are older than age 50 and have gone through menopause. Sixty years old is the average age at diagnosis, according to the American Society of Clinical Oncology (ASCO).

Increased number of menstrual cycles: Women who have had more menstrual cycles in their lifetime have an increased endometrial cancer risk. This includes those who started their periods before age 12 and who went through menopause after age 50.

No pregnancies: Researchers are investigating why pregnancy seems to reduce the risk of endometrial cancer. During pregnancy, a woman’s hormonal balance shifts, with her body producing more progesterone and less estrogen.

Infertility: Irregular menstrual cycles and infertility also may cause imbalances in estrogen and progesterone levels, which may increase the risk of endometrial cancer.

Body

Obesity: Fat tissues tend to produce higher levels of estrogen, particularly after menopause, which increases the endometrial cancer risk for older, overweight women. Women who have a higher body mass index (BMI) have an elevated risk of endometrial cancer. As many as 70 percent of uterine cancer cases are thought to be due, in part, to obesity, according to the ASCO.

Metabolic syndrome: This syndrome occurs when a specific set of conditions develop at the same time, such as extra fat around the abdomen, high blood sugar, high blood pressure, high levels of triglycerides and low levels of high-density lipoproteins in the blood.

Endometrial hyperplasia: This condition occurs when a buildup of cells and glandular structures causes a thickening in the endometrium (the lining of the uterus). There are several types of endometrial hyperplasia, including:

  • Simple hyperplasia
  • Complex hyperplasia
  • Simple atypical hyperplasia
  • Complex atypical hyperplasia

Hyperplasia is not cancer, but the condition may increase the risk of developing cancer, depending on the type of hyperplasia, whether the cells in the endometrium have become abnormal, and other factors. Endometrial hyperplasia most often occurs in women after menopause and may be caused by an imbalance of excess estrogen without progesterone. Obesity, other medical conditions and a family history may increase the risk of developing hyperplasia.

The most common type of endometrial hyperplasia—simple hyperplasia—rarely becomes cancer. Women with “atypical” hyperplasia are more at risk. About 8 percent of untreated simple atypical hyperplasia cases and 29 percent of untreated complex atypical hyperplasia cases become cancer, according to the American Cancer Society (ACS). Hormone therapy may be used to treat this condition and prevent it from turning into cancer. Simple hyperplasia may resolve without treatment.

Polycystic ovary syndrome (PCOS): This condition causes women to have imbalanced hormone levels, including too much estrogen and androgen and too little progesterone. High estrogen levels coupled with low progesterone levels make women with PCOS more vulnerable to developing endometrial cancer. PCOS often causes infertility, which is also a risk factor for endometrial cancer.

Prior pelvic radiation therapy: Patients who have undergone radiation therapy in the pelvic area for cancer in the past may face an increased risk of developing endometrial cancer. Radiation may damage the DNA within cells, which may increase the odds that these cells turn into cancer.

Breast or ovarian cancer: Breast, ovarian and endometrial cancer share many of the same risk factors, especially those related to diet, hormones and reproduction. As a result, breast or ovarian cancer survivors may have an elevated risk of developing endometrial cancer.

Hypothyroidism: This causes a decrease in the production of important hormones and has been linked to endometrial cancer. Studies have found that endometrial cancer patients have higher rates of hypothyroidism and that endometrial cancer sometimes seems to be linked to a past diagnosis with thyroid disease. However, more research is needed to confirm the association.

Race: Uterine cancer is more common among white women compared with other races and ethnicities. While Black women develop uterine cancer less often than white women overall, Black women are more likely to have advanced uterine cancer at the time of diagnosis. Aggressive uterine tumors are also more likely to develop among Black and Hispanic women.

Diabetes: Endometrial cancer is more common among women with type 2 diabetes—about two times more common than the average population, according to the ACS. However, it’s unclear whether diabetes itself is linked to endometrial cancer or whether the association between diabetes and obesity is responsible for the increased risk.

Ovarian tumors: A type of ovarian cancer tumor called a granulosa cell tumor may produce estrogen that stimulates the growth of the uterine lining, which may lead to endometrial cancer. Sometimes, women may experience abnormal bleeding related to endometrial cancer that leads them to discover an ovarian tumor.

Previous treatment

Estrogen replacement therapy: Replacing estrogen without increasing progesterone levels after menopause may increase a woman’s risk of developing endometrial cancer.

Tamoxifen: A drug indicated for the prevention and treatment of breast cancer, called tamoxifen, may spur increased growth of the uterine lining in some post-menopausal women, raising the risk of endometrial cancer. However, tamoxifen is very rarely linked to endometrial cancer. Women with breast cancer who are taking or considering taking tamoxifen should balance the potential benefits of the drug with the low risk of endometrial cancer. Your doctor should be able to address these concerns. If you’re taking tamoxifen, you’ll be advised to pay attention to any unusual bleeding that may potentially indicate endometrial cancer.

Genetic risk factors

Heredity plays a key role in the development of certain gynecologic cancers, because damage to genes involving cell growth and DNA repair accumulate over time.

A family history of cancer does not necessarily mean you are at high risk for developing the disease. About 5 percent of uterine cancers are linked to hereditary factors.

If several members of your family have had endometrial cancer or Lynch syndrome (also known as hereditary non-polyposis colorectal cancer) you may be a candidate for genetic testing.

Lynch syndrome may be caused by a mutation in any of several mismatch repair genes. These genes are normally responsible for repairing damaged DNA. When one of these genes isn’t working, cells may develop mistakes in their DNA, potentially leading to other gene mutations and, eventually, cancer. Lynch syndrome patients face higher risks of both colorectal and endometrial cancers. The lifetime risk of developing endometrial cancer among women with Lynch syndrome is as high as 70 percent, according to the ACS. Between 2 percent and 5 percent of endometrial cancer cases are linked to Lynch syndrome, according to ASCO.

Women who inherit mutations in the BRCA genes or the PTEN gene may also be at an increased risk for developing endometrial cancer.

Uterine sarcoma risk factors

It is not yet known what causes most uterine sarcomas, but certain risk factors have been known to play a role. Risk factors for uterine sarcoma include:

Radiation therapy to the pelvic area: Such treatments, typically to target a different cancer type, increases a woman’s risk of uterine cancer later. Radiation damages even healthy cells, which may lead to cancer. Uterine sarcomas that develop because of radiation exposure typically occur five to 25 years after the treatment.

Race: Uterine sarcomas are about twice as common in African-American women as they are in white or Asian women.

History of retinoblastoma: This type of eye cancer is caused by an abnormal gene and is linked to a higher risk of uterine sarcoma.

Prevention and screening

The exact cause of a woman’s endometrial cancer or uterine sarcoma may never be known. But there are steps women can take to prevent or reduce the risk of developing uterine cancer, including:

Consider birth control: Speak with your doctor about taking birth control pills that combine estrogen and progesterone. Using a progestin-secreting intrauterine device (IUD) may also reduce risk. Discuss the risks and benefits of hormone replacement therapy.

Know your family history: Women who have a hereditary cancer syndrome, such as Lynch syndrome, or a family history of uterine cancer or other cancers may be at higher risk. Knowing your genetics and family history may help you make decisions on screening regimens and prophylactic measures that may help prevent the disease or catch it early.

Lose weight: Obesity is a risk factor for developing uterine sarcoma and endometrial cancer. Regular exercise and maintaining a healthy weight may reduce your risk of developing these and other cancers.

Manage your diabetes: Maintaining blood sugar levels may help reduce your risk of developing uterine cancer.

See your doctor: Get regular checkups with a gynecologist and address issues such as abnormal bleeding or pain.

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