Before menopause, the ovaries normally produce two main types of hormones: estrogen and progesterone. Estrogen promotes endometrial cell growth; progesterone inhibits it. Endometrial cancer is more common in women who have consistently high circulating levels of estrogen and low levels of progesterone. Any factor that leads to increased relative exposure to estrogen over time also leads to an increased risk of endometrial cancer.
The key risk factors for endometrial cancer are:
- obesity — particularly being more than 50 pounds overweight (fat tissue can convert other hormones in the body into estrogens)
- early menstruation (periods starting before age 12)
- late menopause (after age 52)
- never having given birth or a history of infertility (an inability to become pregnant)
- ovarian diseases, such as polycystic ovaries, that may cause a woman to have higher-than-normal estrogen levels and lower-than-normal progesterone levels
- tamoxifen use (see below)
White women are 70 percent more likely than African-American women to develop endometrial cancer. There is some evidence that the occurrence of endometrial cancer tends to run in families. A small number of these cancers may be attributable to a genetic factor that increases the risk of 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 endometrial, ovarian, and colorectal cancers.
If several members of your family have had endometrial or colon cancer, you might want to consider having genetic counseling and genetic testing. To learn more, visit the Hereditary Cancer & Genetics section of this Web site.
Gynecologist and geneticist Noah Kauff outlines risk factors and screening for ovarian and endometrial cancers in women with Lynch syndrome.
The drug tamoxifen, traditionally thought to oppose the action of estrogen, is often used to treat and prevent breast cancer. Despite its antiestrogen effect on the breast, tamoxifen works like estrogen in some respects, countering osteoporosis, for example. Like estrogen, tamoxifen also promotes endometrial growth — putting women who use the drug at increased risk of developing uterine cancer. The risk of developing endometrial cancer from tamoxifen therapy is small, however (less than one in 500), and can be more than balanced by the benefits of breast cancer treatment and prevention.
Based on Memorial Sloan Kettering's eight-year study of women receiving tamoxifen therapy for breast cancer, our doctors recommend that women who take tamoxifen receive yearly gynecologic examinations and immediately report any signs of nonmenstrual vaginal bleeding (including spotting and abnormal vaginal discharge) to their doctor. Clinical tests such as biopsies and sonograms may be conducted on the rare occasion that a patient notices these early signs of abnormal vaginal bleeding. Most important, bleeding typically occurs early enough to detect endometrial cancer when it is most curable. Women who have breast cancer, or who are at risk for it, will want to discuss this issue with their cancer care team.
Hormone Replacement Therapy
Hormone replacement therapy (HRT) uses estrogen, usually in combination with progestins, to offset the effects of menopause, such as those related to bone density. Because unopposed estrogen increases a woman's risk of endometrial cancer, it is almost never prescribed alone in women who still have a uterus.
Alternatives to HRT under investigation include a new class of drugs called selective estrogen response modifiers (SERMs). Research on these “designer estrogens” began after the discovery of tamoxifen, which mimics some of the effects of estrogen. The first SERM to become available, raloxifene, appears to act like estrogen in that it combats osteoporosis, but it also appears to oppose estrogen's effects in the breast and uterus. Memorial Sloan Kettering researchers are now taking part in the multicenter Study of Tamoxifen and Raloxifene (STAR) Trial to determine the comparative benefits and side effects of estrogen and raloxifene. (See April 17, 2006, announcement of initial results of the STAR trial.)
To treat some of the other symptoms of menopause, there are additional alternatives to HRT. For example, certain types of antidepressants and neurologic agents may be prescribed for hot flashes, and vaginal suppositories for vaginal dryness. To learn more about the range of follow-up care offered for women treated with gynecologic cancers, visit the Survivorship & Support section of this cancer information overview.
Hyperplasia refers to an increase in the number of cells in the uterine lining; these cells are usually not cancerous, but they can develop into cancer over time. Common symptoms of hyperplasia include heavy bleeding during or between periods, and bleeding after menopause. It is most common after age 40.
If you have endometrial hyperplasia, your doctor may recommend one of the following treatments: hormone therapy; dilation and curettage (D&C), a procedure that involves the surgical removal of the uterine lining; or hysterectomy, a surgical procedure to remove the uterus. Regular follow-up examinations may also be necessary. Memorial Sloan Kettering has conducted a clinical trial in women with endometrial hyperplasia to better understand this disorder and to develop effective therapies.
All women can help reduce their risk of endometrial cancer by following a low-fat diet, receiving an annual gynecologic examination, and reporting any vaginal bleeding other than menstrual bleeding to their healthcare providers. Using oral contraceptives can also reduce the risk of developing endometrial cancer.
Studies to assess the risk factors associated with endometrial cancer are currently underway in clinical trials at Memorial Sloan Kettering. By conducting surveys of both women who have uterine cancer and women who do not, researchers seek to better understand how diet, lifestyle, family medical history, and genetics influence a woman’s risk of uterine cancer.