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In the United States, endometrial cancer is the most common gynecologic malignancy. Worldwide each year, 287,100 women are diagnosed with this disease (Jemal, 2011). Risk factors include obesity and advancing age. Moreover, as both of these become more prevalent, the incidence of endometrial cancer will likely similarly increase. Fortunately, patients typically seek medical attention early due to vaginal bleeding, and endometrial biopsy leads quickly to diagnosis. The primary treatment is hysterectomy with bilateral salpingo-oophorectomy (BSO) and staging lymphadenectomy for most women. Three quarters will have stage I disease that is curable by surgery alone. Patients with more advanced disease typically require postoperative combination chemotherapy, radiotherapy, or both.

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During their lifetime, one in 38 American women (3 percent) will develop endometrial cancer. In the United States, 46,470 new cases are estimated to develop in 2011, but only 8120 deaths are expected. Most patients are diagnosed early and are subsequently cured. As a result, endometrial cancer is the fourth leading cause of cancer, but only the eighth leading cause of cancer deaths among women (Siegel, 2011). The average age at diagnosis is in the early 60s (Creasman, 1998; Farley, 2000; Madison, 2004).

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Numerous risk factors for developing endometrial cancer have been described (Table 33-1). In general, most risk factors are associated with direct or indirect creation of an excessive estrogen environment.

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Table Graphic Jump Location
Table 33-1. Risk Factors for Endometrial Cancer 
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Of these, obesity is the most common cause of endogenous overproduction of estrogen. Excessive adipose tissue increases peripheral aromatization of androstenedione to estrone. In premenopausal women, elevated estrone levels trigger abnormal feedback in the hypothalamic-pituitary-ovarian axis. The clinical result is oligo- or anovulation. In the absence of ovulation, the endometrium is exposed to virtually continuous estrogen stimulation without subsequent progestational effect and without menstrual withdrawal bleeding.

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Unopposed estrogen therapy is the next most important potential inciting factor. Fortunately, the malignant potential of continuous or sequentially administered estrogen was recognized more than three decades ago (Smith, 1975). Currently, it is rare to encounter a woman with a uterus who has taken unopposed estrogen for years. Instead, combined estrogen plus progestin hormonal therapy is ...

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