Although doctors are not certain of the exact cause of most cases of endometrial cancer, or endo cancer, there are a number of risk factors that are strongly linked to this affliction. The most prevalent gynecological cancer in women, endometrial malignancy is diagnosed when the cells in the inner lining of a woman’s uterus, known as the endometrium, grow incessantly and uncontrollably. It may also be referred to as endometrial carcinoma and is the most common type of uterine cancer. Here’s a rundown of some of the most common risk factors that contribute to endometrial cancer causes.

1. Hormones: The Fundamental Factor

Scientists have established that endometrial cancer cells are covered with receptors for two specific hormones that are already present in a woman’s body: estrogen and progesterone. Typically, these two hormones work in concert, but in some cases, patients may end up with too much unopposed estrogen. This means there is not enough progesterone in the body to balance the extra estrogen. When an overabundance of these hormones is present, the cancer cells pick them up with these receptors, and become a cause of endometrial thickening. Too much abnormal growth results in cancer, making hormones likely the most common cause of endometrial cancer. 

There are a number of actions that can affect the body’s hormone levels, including certain birth control measures, taking supplemental estrogen, certain types of ovarian tumors, and a condition called Polycystic Ovarian Syndrome, or PCOS.

2. Endometrial Cancer and PCOS

PCOS is surprisingly common, affecting 4-12% of adult females. Endometrial thickness in PCOS is often considerable, due to the conditions of the disease itself that compromise normal shedding of the uterine lining, increasing a sufferer’s risk of developing endometrial cancer. In fact, patients with PCOS are five times as likely to develop endometrial cancer. 

3. Extended Menstruation

Women who start their period earlier in life, and those who experience late menopause are experiencing increased risks for endometrial cancer. This is due to the risk of increased exposure to estrogen secretion as the body experiences its natural cycles.

4. Cyclical Concerns

Disruptions in the normal menstrual cycle are sometimes associated with an increased risk for endometrial cancer. Complications such as anovulation, the failure of the ovary to release an egg as scheduled, increase the chance of a diagnosis. Amenorrhea, the temporary or extended absence of menstrual periods, and infertility, are also pre-existing disorders that are often seen in endometrial cancer patients. Again, these challenges are often associated with estrogen and progesterone overproduction. 

5. Endometriosis Can Cause Cancer

Not surprisingly, endometriosis can cause cancer in the endometrium, with its presence noted as an increased risk factor not only in endometrial cancer but breast cancer as well. Like the cancer itself, endometriosis is a disease that is heavily impacted by estrogen levels, suggesting that women who are already affected by this condition may also have extra unopposed estrogen that could contribute to cancer risk. 

6. Obesity

Obesity, often in conjunction with type II diabetes, is a risk factor for endometrial cancer. These conditions are correlated with hyperinsulinemia, or increased levels of insulin in the blood. This lowers the levels of SHBG, a blood protein that is responsible for binding estrogen and other sex hormones. Without enough SHBG to subdue it, there are higher levels of free estrogen circulating around the body. The risk of endometrial cancer is doubled in women who are overweight, and triples in women classified as obese. 

7. Family History

As is the case with several cancers, family history plays a role in a patient’s possibility for developing endometrial tumors. This is due to inherited mutations of certain genes. Even if one does not develop hereditary endometrial cancer as a result of the gene mutation, they may continue to be a carrier, passing the allele onto the next generation. If you believe you have a family history of any cancer, talk to your doctor about genetic testing. Studies have shown that most people feel less stress knowing their risk levels, no matter if they are high or low.

8. Can Tamoxifen Cause Endometrial Cancer?

Tamoxifen is an innovative drug that is used to treat and prevent breast cancer. It has been shown effective against certain types of breast tumors and may be used in conjunction with other treatments like radiation, immunotherapy, or chemotherapy and even preventative mastectomies. If a patient is determined to be at high risk of breast cancer, they may be prescribed Tamoxifen in hopes of decreasing the formation of cancerous tumors. Tamoxifen has also demonstrated effectiveness in certain off-label uses, such as preventing certain types of arteriosclerosis and utilization in fertility treatments.

However, when present in the uterus, Tamoxifen acts as an estrogen, and can contribute to the growth of the endometrium, especially in women who have gone through menopause. The risk of developing cancer from Tamoxifen has been established, but is considered relatively low, and its benefits in relation to breast cancer and other health concerns must be considered along with its risks. Those who take the drug should monitor themselves for endometrial thickening symptoms, such as unusual bleeding, and discuss them with their gynecologist. 

Women who are concerned about their risk factors for endometrial cancer should speak to their healthcare provider about managing and mitigating their risk. For New York City patients, SHAREing &CAREing can help with locating providers in NYC, furnishing support, and connecting patients to screening in the Queens area. 

Sources

• “The Association Between Endometriosis and Risk of Endometrial Cancer and Breast Cancer: A Meta-analysis”, BMC Women’s Health, 2022
• “Endometrial Cancer”, StatPearls, National Library of Medicine, 2022.
• “Endometrial Cancer Causes, Risk Factors, and Prevention”, American Cancer Society, 2024. 
• “Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium”, Frontiers in Physiology, 2021.
• Risk of Endometrial Cancer in Patients With Polycystic Ovarian Syndrome: A Meta‑analysis, Oncology Letters, 2023
• “Unopposed Estrogens :Current & Future Perspectives, European Review for Medical and Pharmacological Sciences, 2022.
• “What is Endometrial Cancer?”, American Cancer Society, 2024.