Before menopause, the ovaries normally produce two main types of hormones: estrogen and progesterone. Estrogen encourages the growth of endometrial cells in the uterus, whereas progesterone inhibits it. When a woman has high circulating levels of estrogen and low levels of progesterone over long periods of time, the risk for uterine cancer rises.
The cells in fatty tissue also make estrogen, which helps explain why obesity is the biggest risk factor for developing this cancer.
The risk for developing uterine cancer is greater if you are obese (50 pounds or more overweight) or if one of the following applies to you:
- Age 50 to 60
- Began menstruating before age 12
- Entered menopause relatively late, after age 52
- Have never given birth
- Have a history of infertility (an inability to become pregnant)
- Have an ovarian disease, such as polycystic ovarian syndrome, that could cause you to have higher than normal levels of the hormone estrogen and lower than normal levels of the hormone progesterone
- Elevated blood sugar (diabetes)
- High blood pressure (hypertension)
- Family history of endometrial carcinoma
Other risk factors include the following:
Genetics — A small number of cases of endometrial cancer are linked to the presence of a genetic factor that increases the risk for the disease. For example, hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is characterized by mutations in specific genes that increase a person’s chances of developing certain uterine, ovarian, and colorectal cancers. For women with Lynch syndrome, the lifetime risk of endometrial carcinoma is 27 to 71 percent compared with 2.6 percent in the general population, and most develop the cancer at a younger age than women with nonhereditary forms of endometrial cancer. Women who inherit mutations in the BRCA genes or the PTEN gene (Cowden’s syndrome) may also be at increased risk of developing endometrial cancer.
If several members of your family have had uterine or colorectal cancer, you might want to consider having genetic counseling and genetic testing.
Tamoxifen — The drug tamoxifen, traditionally thought to oppose the action of estrogen, is often used to treat and prevent breast cancer. But despite its anti-estrogen effect on the breasts, tamoxifen works like estrogen in some other respects, such as countering the thinning of the bones, a disease known as osteoporosis. Like estrogen, tamoxifen also promotes endometrial growth, which puts postmenopausal women who currently take the drug (or have taken it in the past) at increased risk of developing uterine cancer. For premenopausal woman, however, there is a lack of evidence that tamoxifen increases the risk of endometrial cancer. The increased risk depends in part on the dose taken and the length of time it’s used. The overall risk for developing uterine cancer after tamoxifen use is small, however, with less than one in 500 women who have taken or are taking the drug experiencing this problem. Women who take tamoxifen should discuss the risks and benefits of this drug with their doctors.
Endometrial hyperplasia — This condition, which involves an increase in the number of cells in the uterine lining, is another risk factor for developing uterine cancer. These cells are usually not cancerous, but certain kinds of hyperplasia can develop into cancer over time. Common symptoms of hyperplasia are similar to those of uterine cancer and include heavy vaginal bleeding during or between periods and bleeding after menopause.
Hormone replacement therapy — Hormone replacement therapy (HRT) uses female hormones to replace the ones your body no longer makes after menopause; it provides estrogen, usually in combination with progestin, to offset the effects of menopause such as loss of bone density. The risk of developing endometrial hyperplasia and endometrial carcinoma with HRT can be significantly reduced by taking progestin at the same time. Because unopposed estrogen (estrogen taken alone) increases a woman’s risk of uterine cancer, it is almost never prescribed as a single hormone for those who have an intact uterus. HRT that includes both estrogen and progestin does not increase the risk of uterine cancer. There are also numerous alternatives to HRT, which you can discuss with your physician.
Preventing Uterine Cancer
In addition to getting regular annual checkups with your gynecologist and reporting any unexpected or abnormal vaginal bleeding, lifestyle measures such as keeping your weight under control with physical activity and following a low-fat diet may help to prevent uterine cancer. Using oral contraceptives has also been associated with a reduced risk.
Gynecologist and geneticist Noah Kauff outlines risk factors and screening for ovarian and endometrial cancers in women with Lynch syndrome.
For women without a strong family history of endometrial or gynecologic cancers, Memorial Sloan Kettering follows the National Comprehensive Cancer Network (NCCN) guidelines for screening. However, if you have a strong family history of endometrial or gynecologic cancers, we provide individual recommendations for continued cancer screening in consultation with the experts in our Hereditary Cancer & Genetics Service that are based on a personal and family risk assessment.
For women with the inherited condition known as Lynch syndrome, we usually recommend gynecologic cancer follow-up care as recommended by your physician in consultation with our experts. We would recommend that other women in your family who have Lynch syndrome be screened for endometrial and ovarian cancer with transvaginal ultrasound one to two times annually beginning at age 30. Annual endometrial biopsies are also recommended starting at this age. Our Hereditary Cancer & Genetics Service experts are also available to discuss risk-reducing surgery.