Endometrial cancer is the most common gynecologic malignancy in the United States. It begins in the lining of the uterus, known as the endometrium. A key feature of endometrial cancer is that it frequently presents early symptoms, allowing for an earlier diagnosis before the disease has advanced.
The most common and important early symptom is abnormal vaginal bleeding, which may include the following: bleeding between menstrual periods, heavier or prolonged menstrual bleeding or any vaginal bleeding after menopause. Postmenopausal bleeding is never normal and should always prompt medical evaluation.
When abnormal bleeding occurs, evaluation typically includes a transvaginal ultrasound to assess endometrial thickness and endometrial sampling (biopsy) to detect cancer or precancerous changes. Prompt evaluation is recommended, particularly for patients over the age of 40 or for anyone with postmenopausal bleeding.
Understanding risk factors
Endometrial cancer is strongly influenced by estrogen exposure, particularly when estrogen is not balanced by progesterone ("unopposed estrogen"). Conditions that increase estrogen exposure raise the risk of abnormal endometrial growth and cancer.
Major risk factors include:
- Obesity: Fat tissue converts other hormones into estrogen; higher body fat leads to increased circulating estrogen levels.
- Chronic anovulation (irregular or absent ovulation), such as in polycystic ovary syndrome (PCOS). Without ovulation, the ovary does not develop the corpus luteum that produces progesterone. The corpus luteum’s primary function is to secrete progesterone. This creates a chronic unopposed estrogen state.
- Estrogen-only hormone therapy after menopause in patients who still have a uterus.
- Nulliparity (never having been pregnant). This exposes the uterus to more estrogen stimulation over time. Pregnancy gives the uterus a long “hormonal break”. Furthermore, during pregnancy, the body makes a large amount of progesterone, a hormone that protects and stabilizes the uterine lining (endometrium).
- Increasing age.
Prolonged estrogen stimulation can lead to endometrial hyperplasia, a precancerous condition that may progress to cancer if untreated.
Additional risk considerations
- Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an inherited genetic condition. Women with Lynch syndrome have a lifetime endometrial cancer risk of about 25%–60%, depending on the gene involved. In contrast, the general population's lifetime risk is about 2%–3%.
- Diabetes and metabolic syndrome.
- Family history of endometrial or colorectal cancer.
Diagnosis
Initial evaluation often includes:
- Transvaginal ultrasound to measure endometrial thickness
- Endometrial biopsy, which is the gold standard for diagnosis
Treatment
Surgery is the primary treatment for most patients and typically includes:
- Removal of the uterus (hysterectomy) with fallopian tubes and ovaries
- Sentinel lymph node mapping, which is now commonly used to assess lymph node involvement while reducing surgical morbidity compared to a more extensive lymph node dissection.
Depending on tumor stage, grade, and molecular features, additional treatments may include:
- Radiation therapy
- Chemotherapy
- Immunotherapy, particularly for tumors with mismatch repair deficiency or microsatellite instability
- Hormonal therapy (for select low-grade, hormone-sensitive tumors)
The importance of early evaluation
Endometrial cancer often sends an early signal through abnormal bleeding. Paying attention to this symptom and seeking prompt medical care can lead to early diagnosis, effective treatment and better long-term outcomes.
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