|
|
|
Uterine Corpus (Endometrium)Louise A. Brinton, Ph.D.*
|
The uterus is a pear-shaped organ that lies in the abdomen between the bladder and the rectum. It consists of the cervix--the opening of the uterus into the vagina--and the corpus, sometimes called the body or womb. The corpus is composed of two layers of tissue. The spongy inside layer--the endometrium--proliferates between menses and is shed during menstruation if fertilization has not occurred. The outside layer, or myometrium, is a muscle capable of expanding during pregnancy to accommodate a growing fetus. Female sex hormones, including estrogen, prepare the uterus for pregnancy. Because most uterine cancers originate in the endometrium, cancers of this site can be assumed to be endometrial in origin unless specifically designated otherwise.
Cancer of the uterine corpus or endometrium is the third most common cancer among U.S. women and accounts for about 9 percent of their cancers. Fortunately, this disease causes a limited number of deaths, as reflected in the 83 percent five-year relative survival rate (Ries et al., 1994). Endometrial cancer is rare before the age of 45, but the risk rises sharply among women in their late 40s to mid 60s. Endometrial cancer rates are highest in North America and northern Europe; intermediate in Israel, southern Europe and Latin America; and low in Asia and Africa. In the United States, the age-adjusted incidence rates for whites are nearly twice as high as those for blacks; the reason for this discrepancy is unknown. Within the last several decades in the United States, there has been a dramatic change in the incidence pattern for endometrial cancer, characterized by a marked increase that peaked about 1975 and subsequently declined (Weiss et al., 1976). Considerable evidence has linked this rise and fall with the widespread use of estrogen replacement therapy in the late 1960s and early 1970s, followed by a dramatic reduction in such usage in the late 1970s. Endometrial cancer and breast cancer share some of the same risk factors (Elwood et al., 1977; Hulka et al., 1980). Factors predisposing to both diseases include high socioeconomic status, never having given birth or having few children, early age at menarche, and late age at menopause. In contrast to breast cancer, late age at first birth has not been found to be a risk factor for endometrial cancer. Multiple births have been linked to a decreased risk of endometrial cancer, with women who have had four or more children having only one-third the risk of women who have never had children. Women who have never had children, particularly those with a history of infertility, are at greatest risk. Studies of women with Stein-Leventhal syndrome, a rare condition characterized by multiple ovarian cysts, excessive estrogen production, and infertility, have been noted to be at particularly high risk for this cancer. Obesity, which is accompanied by increased levels of endogenous estrogens, has long been recognized as a risk factor for endometrial cancer, with very heavy women having disproportionately high risks (Swanson et al., 1993). Certain diseases that occur more commonly among overweight women, such as diabetes, high blood pressure, and gallbladder disease, have been linked with the occurrence of endometrial cancer, but it is unlikely that these conditions have independent effects on risk. Despite extensive evidence linking obesity to the occurrence of endometrial cancer, few studies have investigated the potential role of dietary factors. There is some evidence of increases in risk with higher intakes of dietary fat (Potischman et al., 1993). Most risk factors for endometrial cancer have been linked with hormonal imbalances, especially excess estrogen production. It is not surprising, therefore, that increased risk has been found among users of estrogen replacement therapy (Brinton et al., 1993; Hulka et al., 1980; Shapiro et al., 1985). Postmenopausal women who use estrogens have an estimated five- to ten-fold increased risk compared with nonusers, with risk increasing even further when use extends over many years or when high dose drugs are used. In most studies, risk appears to decrease rapidly with discontinuation of the estrogens (Hulka et al., 1980), although several studies suggest that elevated risk may continue for some time (Shapiro et al., 1985). To combat the adverse effects of estrogens on endometrial tissue, it has become commonplace for estrogens to be given in combination with a progestogen. Whether the combined therapy entirely eliminates the excess risk associated with estrogens alone has yet to be resolved (Brinton et al., 1993). In contrast to menopausal estrogens, oral contraceptives containing both an estrogen and a progestin have been linked with lowered risks of endometrial cancer (Cancer and Steroid Hormone Study, 1987; Henderson et al., 1983; Weiss and Sayvetz, 1980). However, an elevated risk was found in users of the sequential oral contraceptives, which included a regimen of a strong unopposed estrogen followed by limited exposure to a relatively weak progestin. These products are no longer marketed. Users of combination oral contraceptives have been found to have approximately half the risk of endometrial cancer compared to nonusers, and the longer the usage, the greater the apparent protection. In several studies, the protective effect of the pill appears most pronounced among high-risk childless women (Cancer and Steroid Hormone Study, 1987; Henderson et al., 1983). |
* From the Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, Bethesda, Maryland
