Endometrial cancer begins in the inner lining of the uterus and ranks as the most common type of cancer affecting the female reproductive system in the United States. Each year, over 66,000 women receive this diagnosis, making it crucial for women to understand the warning signs, risk factors, and what steps they can take to protect their health. Early detection often leads to successful treatment outcomes, as this cancer frequently causes noticeable symptoms in its early stages.

Epidemiology

Endometrial cancer represents the most widespread cancer affecting the reproductive organs of women in the United States. In 2023 alone, more than 66,000 new cases were anticipated, with over 13,000 deaths attributed to uterine cancers, most of which were endometrial in origin. This cancer makes up approximately 83 percent of all uterine corpus cancers reported, with the remaining cases consisting of rarer forms such as uterine sarcomas.^[4]

Globally, endometrial cancer stands as the sixth most common cancer affecting women, with 417,000 new cases and 97,000 deaths recorded in 2020. The burden of this disease has been growing rather than shrinking. Unlike many other cancers that have seen improvements in survival rates, endometrial cancer is among the few cancers showing increased mortality rates over the past decade, with a rise of 1.7 percent in overall deaths.^[13]

The typical patient diagnosed with endometrial cancer is in her mid-60s, as most cases occur after menopause (the permanent end of menstrual periods). Approximately 3 percent of women will face a diagnosis of uterine cancer at some point during their lives. While the cancer can develop at any age, it remains relatively uncommon in younger women and becomes more frequent as women grow older.^[5][8]

Causes

Medical researchers have not pinpointed one single cause of endometrial cancer. Instead, the disease appears to develop when something triggers changes in the cells that line the uterus. These mutated cells (cells with abnormal changes in their genetic material) begin to grow and multiply without normal controls. As they accumulate, they can form a mass called a tumor.^[5]

The disease starts in the endometrium, which is the inner lining of the uterus. This lining naturally changes throughout a woman’s menstrual cycle. Hormones called estrogen and progesterone cause the endometrium to thicken each month in preparation for a possible pregnancy. When pregnancy does not occur, the body produces less progesterone, causing the endometrial lining to shed during menstruation. Problems arise when estrogen acts on the endometrium without enough progesterone to balance it, leading to excessive thickening and, in some cases, cancer development.^[5]

Unlike some cancers, endometrial cancer is not an infectious disease and cannot be transmitted from one person to another. It develops through a complex interaction between genetic factors, hormones, and lifestyle influences.^[1]

Risk Factors

Several factors can increase a woman’s chances of developing endometrial cancer. Many of these risk factors relate to the balance between estrogen and progesterone in the body. When estrogen levels remain high without sufficient progesterone to counteract them, the endometrium may grow too thick, creating conditions that favor cancer development.^[2]

Age stands as one of the most significant risk factors. Older age increases the likelihood of developing most cancers, and endometrial cancer follows this pattern. Most diagnoses occur in women who are going through or have completed menopause, typically in their mid-60s.^[6]

Obesity represents a major risk factor for endometrial cancer in many countries. Women who are overweight or have a body mass index of 25 or greater face substantially higher risk. As body mass index increases, so does the risk of developing this cancer. Excess body fat can produce additional estrogen, contributing to the hormonal imbalance that promotes endometrial cancer.^[2][6]

Reproductive history plays an important role in risk. Women who have never given birth face higher risk than those who have had children. Starting menstrual periods at an early age or entering menopause later in life also increases exposure to estrogen over a lifetime, raising cancer risk. Each of these situations means more years of estrogen stimulating the endometrium.^[2]

Certain medical conditions elevate risk as well. Women with polycystic ovary syndrome (PCOS), a hormonal disorder that affects the ovaries, face increased risk due to irregular periods and hormonal imbalances. Having metabolic syndrome or type 2 diabetes also increases the likelihood of developing endometrial cancer.^[2]

Family history matters, particularly for women with a first-degree relative such as a mother, sister, or daughter who had endometrial cancer. Certain inherited genetic conditions, especially Lynch syndrome, significantly increase the risk of developing endometrial cancer along with other cancers such as colon and ovarian cancer. Women with a personal history of breast, ovarian, or colon cancer also face higher risk.^[2]

A condition called endometrial hyperplasia, where the endometrium becomes abnormally thick, can lead to cancer if not monitored and treated. This precancerous condition often causes abnormal bleeding and requires prompt medical attention.^[2]

Symptoms

Endometrial cancer often announces itself through noticeable symptoms, which is one reason why many cases are detected early. The most common and important warning sign is abnormal bleeding from the vagina. For women who have already gone through menopause, any vaginal bleeding or spotting, even just a small amount, is considered abnormal and should be evaluated by a healthcare provider.^[1][2]

For women who have not yet reached menopause, warning signs include bleeding between periods, unusually heavy or prolonged menstrual bleeding, or any irregular bleeding pattern. Women over age 40 who experience extremely heavy, frequent, or prolonged vaginal bleeding should seek medical evaluation, as these symptoms may indicate endometrial cancer or other serious conditions.^[5]

Pain in the pelvis represents another potential symptom. This discomfort may feel like lower abdominal pain or cramping in the area just below the belly. Some women experience this pain during sexual intercourse as well.^[1][2]

Changes in urination or bowel habits can signal advanced endometrial cancer. Difficulty urinating, pain during urination, or changes in bowel movements may occur if the cancer has grown large enough to affect nearby organs. Some women notice thin, white, or clear vaginal discharge if they are postmenopausal.^[5]

In more advanced cases, women may experience abdominal bloating, feeling full quickly when eating, or unexplained weight loss. These symptoms typically appear when the cancer has progressed beyond its early stages.^[6]

It’s important to remember that these symptoms can be caused by many conditions other than cancer, including fibroids, polyps, or hormonal changes. However, any unusual or persistent symptoms warrant a visit to a healthcare provider for proper evaluation and diagnosis.^[1]

Prevention

While no method can completely prevent endometrial cancer, women can take several steps to reduce their risk. Managing weight through healthy eating and regular physical activity stands as one of the most effective preventive measures. Maintaining a healthy body weight helps regulate hormone levels and reduces excess estrogen production associated with obesity.^[5]

Eating a nutritious diet rich in fruits and vegetables may help lower risk. Research suggests that following a Mediterranean-style diet, which emphasizes plant-based foods, healthy fats, and limits red meat and dairy products, may reduce the risk of developing endometrial cancer. The goal is to fill at least half of each plate with colorful fruits and vegetables, which contain protective compounds called antioxidants that help defend cells from damage.^[22]

Regular physical activity provides protective benefits beyond weight management. Exercise helps regulate hormones, reduces inflammation, and supports overall health. Healthcare providers can help women determine what types and amounts of physical activity are appropriate for their individual circumstances.^[5]

For women taking hormone therapy during menopause, the type of hormones matters. Women with a uterus who use estrogen therapy should take it combined with progesterone rather than estrogen alone. This combination prevents the endometrium from becoming too thick and substantially decreases cancer risk. Women should discuss the benefits and risks of any hormone therapy with their healthcare provider.^[6]

Managing chronic health conditions, particularly diabetes, can help reduce risk. Working closely with a healthcare team to control blood sugar levels and maintain metabolic health provides multiple benefits, including potentially lowering endometrial cancer risk.^[5]

Women with endometrial hyperplasia need careful monitoring and treatment to prevent progression to cancer. Regular follow-up appointments and appropriate treatment of this precancerous condition can stop cancer before it starts.^[5]

For women with Lynch syndrome or other genetic conditions that increase risk, more aggressive prevention strategies may be appropriate. Genetic counseling can help these women understand their risks and make informed decisions about prevention options, which in some cases may include preventive surgery after childbearing is complete.^[2]

Pathophysiology

Understanding how endometrial cancer develops requires knowing how the normal endometrium functions. Throughout a woman’s reproductive years, the endometrium undergoes monthly cycles of growth and shedding controlled by hormones. Estrogen causes the endometrial lining to thicken and grow during the first half of the menstrual cycle. After ovulation, progesterone keeps this growth in check and prepares the lining for a possible pregnancy. Without pregnancy, hormone levels drop, and the thickened lining sheds during menstruation.^[5]

Endometrial cancer develops when this carefully regulated process goes wrong. Prolonged exposure to estrogen without adequate progesterone causes the endometrium to grow excessively. Over time, this continuous stimulation can cause cells in the endometrium to undergo genetic changes or mutations. These altered cells may begin to grow and divide more rapidly than normal cells, and they may fail to die when they should.^[1]

As abnormal cells accumulate, they can form a tumor within the endometrial lining. If left unchecked, cancer cells can invade deeper into the muscular wall of the uterus called the myometrium. From there, they may spread to other nearby organs such as the cervix, fallopian tubes, ovaries, or vagina. Eventually, cancer cells can enter the lymphatic system or bloodstream and travel to distant parts of the body, a process called metastasis.^[1]

Medical science has identified different types of endometrial cancer based on how the cells appear under a microscope and their genetic characteristics. Type 1 endometrial cancers, which represent about 80 percent of cases, typically grow slowly and are often detected early. These cancers usually develop in the presence of excess estrogen. Type 2 endometrial cancers are less common but tend to be more aggressive, growing and spreading more rapidly. They include rarer forms such as serous and clear cell carcinomas.^[4]

Recent research has revealed that endometrial cancers can be further classified based on their molecular characteristics, which means looking at specific genetic changes within the cancer cells. This molecular classification helps doctors understand how aggressive a particular cancer might be and which treatments are most likely to work. Some endometrial cancers have specific genetic changes that make them respond to certain targeted therapies or immunotherapies.^[13]

The staging system describes how far cancer has spread from its original location. Stage I cancer remains confined to the uterus. Stage II has extended to the cervix. Stage III has spread to the vagina, ovaries, or lymph nodes in the pelvis or abdomen. Stage IV, the most advanced, has reached the bladder, bowel, or distant organs. The stage at diagnosis strongly influences treatment decisions and outlook for recovery.^[6]