Endometrial Cancer: Overview and Risk Factors

Cancer of the endometrium, the mucous membrane lining the uterus, makes up about 90% of uterine cancers. With approximately 40,000 cases annually, it is the most common gynecologic cancer in the United States. Epithelial and muscle cells of the uterus have potential for malignant transformation and constitute the 2 main histologic types of uterine cancer: adenocarcinoma and sarcoma. Adenocarcinoma, the most common uterine malignancy, will be the focus of this chapter.

Abnormal vaginal bleeding is the most common symptom of endometrial cancer, but a woman may also experience abdominal pain, dysuria, and/or dyspareunia. Vaginal bleeding in any postmenopausal woman should be considered uterine cancer until proven otherwise.

Type 1 endometrial carcinomas demonstrate a response to estrogen, whereas type 2 carcinomas do not. Because type 2 tumors lack well–identified risk factors, the following risk factors relate to type 1 endometrial carcinoma.

Risk Factors

Although endometrial cancer is more common in Caucasians, African Americans often have worse outcomes with the disease.¹

The following factors are also associated with risk:

• Obesity. A majority of patients diagnosed with endometrial cancer at a young age are obese.² Some studies have found that a high body mass index (BMI) and low physical activity were strong and independent risk factors for endometrial cancer.³ The relationship between obesity and cancer may be explained by obesity–related elevations in hormones and growth factors.⁴ Peripheral conversion of androgens to estrogen in adipose tissue leads to greater endogenous estrogen concentrations in obese persons.
• Age. Endometrial cancer risk increases with age, and the disease generally affects women over 50 years.
• Menopausal Estrogen Therapy. Unopposed estrogen increases risk for endometrial cancer. The combined use of estrogen and progestin is not associated with increased risk.
• Diabetes.
• Hypertension.
• Polycystic ovary syndrome (PCOS). Anovulation from PCOS or another cause results in persistent unopposed endogenous estrogen.
• Prolonged exposure to estrogen. Early menarche, late menopause, and nulliparity (especially when due to anovulation) possibly increase the risk for uterine malignancy.
• Genetics. A family history of hereditary nonpolyposis colorectal cancer greatly increases the risk of uterine carcinoma.
• Estrogen–secreting tumors or history of estrogen–responsive cancer.
• Decreased sex–hormone binding globulin levels.

Oral contraception, multiparity, and exercise are considered protective.