Causes
The most important risk factors for endometrial cancer have to do with the hormone estrogen. Basically, high levels of estrogen increase the risk of endometrial cancer. Because cumulative lifetime exposure to estrogen is what counts, older women are at much higher 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.
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 tumor 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, the greater the protective effect.
Estrogen supplements (or hormone replacement therapy, HRT), used to relieve the symptoms of menopause and prevent osteoporosis, may slightly increase the risk of endometrial cancer. However, estrogen is usually given in combination with another type of hormone called progestins, which counteract the effects of estrogen on the endometrium and negate the endometrial cancer risk. Modern 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 cause endometrial cancer 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 very much higher than the added risk of uterine cancer.
Obesity is a strong risk factor. This is because fatty tissue in women produces large amounts of estrogen, and does so year-round, without a break. Overweight women are three to ten times more likely than average to develop endometrial cancer, depending on how much extra weight they carry and how long they have carried it. Diets high in fat can be a risk in itself, while physical activity can be protective even without the added benefits losing weight may have.
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.