The most important risk factor for endometrial cancer has to do with the hormone estrogen. Estrogen stimulates the lining of the uterus (the endometrium) to grow. Women with high levels of estrogen in their bodies are at increased risk of endometrial cancer. Because cumulative lifetime exposure to estrogen is what counts, and older women are at highest risk. Most endometrial cancers appear after menopause, and the risk continues to climb with each successive decade. About 95% of these cancers occur in women over the age of 40.
Obesity is a strong risk factor for endometrial cancer. This is because fatty tissue in women produces large amounts of estrogen, and does so continuously. Overweight women are 3 to 10 times more likely than average to develop endometrial cancer, depending on how much extra weight they carry and how long they have carried it. A diet high in fat can be a risk factor in itself. Physical activity can be protective even without the added benefits that losing weight may have.
Estrogen is produced in each menstrual cycle, and women who have had more menstrual cycles are at higher risk. This means that a 40-year-old woman whose first period came at age 11 is more likely to get an endometrial tumour than a 40-year-old who began menstruating at age 14. Since pregnancy interrupts these cycles, women who have had children are at lower risk than those who haven't. The more pregnancies a woman has had, the greater the protective effect. However, the number of menstrual cycles and pregnancies a woman has is a much smaller risk factor for developing endometrial cancer than the risk associated with obesity.
Estrogen supplements (or hormone replacement therapy, HRT), used to relieve the symptoms of menopause, may slightly increase the risk of endometrial cancer. However, estrogen is usually given in combination with another type of hormone called progesterone, which counteracts the effects of estrogen on the endometrium and negates the endometrial cancer risk. Oral contraceptive pills, in which the progesterone effect outweighs the small estrogen dose, even appear to offer some protection against endometrial cancer. Progesterone is the dominant hormone during a normal menstrual period. Therefore, younger women who don't menstruate normally (unless they're on the pill) are at higher risk of endometrial cancer.
Because of its estrogen-like effects, tamoxifen citrate*, a common medication for patients with breast cancer, has been thought to increase the risk of endometrial cancer 3 to 5 times in women who may be taking it to prevent the recurrence of breast cancer. However, the risk of recurrence of breast cancer without tamoxifen citrate in those women who are prescribed the medication is much higher than the added risk of uterine cancer. If you are taking this medication, your doctor may arrange for regular monitoring to help detect early cancerous changes in the uterine lining.
People with a family history of this disease, and people in families with some types of inherited colon cancer or breast cancer may be at increased risk.