7 Endometrial Cancer Risk Factors: Breast or Ovarian Cancer History and More

Medically reviewed by Danielle Leonardo, M.D.
Written by Emily Wagner, M.S.
Posted on September 6, 2023

If you or a loved one received a diagnosis of endometrial cancer, you may be concerned about whether other relatives are at high risk of this disease. Many factors, including family history, do appear to play a role in the development of endometrial cancer. You can influence some of these risk factors, but others are outside your control.

In this article, we’ll discuss factors that raise the risk of developing endometrial cancer. Knowing your individual risk can help you make healthier decisions and encourage other family members to understand their risk as well.

Estrogen and Its Role in Endometrial Cancer

Estrogen is a sex hormone that’s mainly made by the ovaries. Your body starts making more estrogen when you have your menarche (first period or menstrual cycle). Estrogen levels tend to fall as you go into menopause, typically between ages 45 and 55.

Doctors and researchers have found that changes in estrogen levels throughout life affect the risk of endometrial cancer. A healthy balance of estrogen and another hormone, progesterone, keeps the endometrium (uterus lining) healthy. Too much estrogen throws off your hormonal balance and can trigger endometrial cells to grow out of control and possibly become cancerous.

Below are seven risk factors and how they may lead to endometrial cancer. Many of these factors relate to estrogen levels. Some people have one or more of these factors, while others diagnosed with endometrial cancer may not have any. Your doctor or gynecologist can help you better understand your individual risk.

1. Personal History of Breast Cancer or Ovarian Cancer

Endometrial cancer is the most common type of gynecologic cancer in the United States. Estrogen levels also affect breast and ovarian cancer, and these three cancers share many known risk factors.

If you’ve had breast cancer, you may be at risk of developing endometrial cancer. Doctors and researchers have found that tamoxifen, a drug used as breast cancer treatment, specifically increases the risk of endometrial cancer.

Tamoxifen blocks breast cancer cells from using estrogen. The drug can also trigger cells in the uterus to grow and divide too quickly, leading to abnormal growths and, in some cases, endometrial cancer. The longer you take tamoxifen, the higher your risk of uterine cancer.

Ovarian tumors can also affect estrogen levels. A type called granulosa cell tumors may overproduce large amounts of estrogen, causing the cells in the uterine lining to grow and divide uncontrollably. If you’re postmenopausal and start having vaginal bleeding, it’s best to make an appointment with your doctor or gynecologist. This symptom could indicate endometrial or ovarian cancer.

Read about new treatments for endometrial cancer.

2. Some Types of Hormone Replacement Therapy

Hormone replacement therapy is used to relieve menopause symptoms. Estrogen therapy may be prescribed to help treat hot flashes and night sweats and prevent the loss of bone density that can lead to osteoporosis. Studies show that taking estrogen alone can increase the risk of endometrial cancer.

If you’re interested in trying hormone replacement therapy for menopause symptoms, your doctor will likely prescribe a combination of estrogen and progestin, a synthetic form of progesterone. Unlike estrogen-only therapies, this combination doesn’t increase the risk of endometrial cancer. You may notice increased vaginal bleeding — if you’re concerned about this side effect, talk to your doctor.

You may have heard that oral contraceptives (birth control pills) also influence your risk of cancer. Birth control pills have actually been found to lower the risk of endometrial cancer.

3. Early Puberty or Late Menopause

Studies show that having more menstrual cycles during your lifetime can raise your risk of endometrial cancer. This is because the more cycles you have, the longer the tissues in your uterus are exposed to estrogen.

If you started puberty early and entered menopause late, you’re more likely to develop this cancer. However, if you began getting your period early but also have early menopause, your risk isn’t affected very much.

4. Infertility or Never Having Children

When you’re pregnant, your body starts making more progesterone than estrogen. This change in your hormonal balance helps lower your risk of endometrial cancer. One study from Denmark found that pregnancy lowered the chances of developing this cancer by nearly half.

Researchers have also found that not becoming pregnant or being infertile (unable to have children) raises the risk of developing endometrial cancer. Researchers who pooled the results of 14 studies reported that women who never gave birth were 1.76 times more likely to develop this cancer compared with those who had given birth.

Infertility is associated with a slight increase in risk of developing endometrial cancer. A handful of studies have linked some types of fertility treatment with an even higher risk. However, more research from larger studies is needed to confirm these findings.

5. Higher Body Mass Index

Having obesity or an increased body mass index (BMI) plays a major role in the risk of developing endometrial cancer. Excess body fat can affect hormone levels, and research shows that fat changes hormones known as androgens into estrogens.

The more cholesterol is converted to estrogen, the greater the risk of endometrial cancer. According to the American Cancer Society, women with a BMI of 25 to 29.9 are twice as likely to have endometrial cancer compared with those within a range of 18.5 to 24.9. For those who have a BMI of 30 or higher, the chances triple.

Having diabetes also brings an increased risk of endometrial cancer. It’s important to note that people with diabetes are less likely to eat a healthy diet or get enough exercise — two other risk factors for endometrial cancer. Researchers haven’t uncovered the exact link between diabetes and endometrial cancer, but there’s evidence that these conditions overlap.

6. Family History of Endometrial Cancer

If a close family member like your mother, sister, or grandmother has had endometrial cancer, you’re more likely to develop it too. One meta-analysis of 16 studies found that women with a family history of endometrial cancer are nearly twice as likely to develop the condition as those without a family history.

Certain changes or mutations in DNA may be passed down in families. Many of these changes affect genes that help repair damaged DNA or control how quickly cells grow and divide.

It’s also common for families with a history of endometrial cancer to have a type of colon cancer known as hereditary nonpolyposis colorectal cancer, or Lynch syndrome. Overall, the risk of a woman developing endometrial cancer during her lifetime is around 3 percent, according to the American Cancer Society. For those with Lynch syndrome, this risk may rise to around 70 percent.

It’s important to note that having a family history of endometrial cancer or Lynch syndrome doesn’t guarantee that you’ll have these conditions as well.

If you have a loved one living with endometrial cancer, read about ways you can support them.

7. Endometrial Hyperplasia

Sometimes abnormal growths known as endometrial hyperplasia form in the uterine lining. These growths are mostly harmless and tend to go away on their own or with hormonal treatment. Atypical hyperplasia can develop when your body has more estrogen than progesterone. This type of abnormal growth increases the likelihood of developing endometrial cancer.

There are two types of atypical hyperplasia — simple and complex. According to the American Cancer Society, there’s an 8 percent to 29 percent chance that these growths will develop into endometrial cancer. If you have atypical endometrial hyperplasia, your doctor or gynecologist will treat it to lower your risk of cancer. The most common symptom of atypical endometrial hyperplasia is abnormal vaginal bleeding.

Read about potential symptoms of endometrial cancer.

Talk With Others Who Understand

On MyEndometrialCancerCenter, the site for people with endometrial cancer and their loved ones, people come together to gain a new understanding of endometrial cancer and connect with others who understand life with endometrial cancer.

Are you living with endometrial cancer or caring for a loved one who’s been diagnosed with it? Do you still have questions about risk factors for endometrial cancer? Share in the comments below.

  1. Endometrial Cancer Risk Factors — American Cancer Society
  2. Estrogen — Cleveland Clinic
  3. What Is Menopause? — National Institute on Aging
  4. Estrogen as an Essential Resource and the Coexistence of ER+ and ER- Cancer Cells — Frontiers in Ecology and Evolution
  5. Key Statistics for Endometrial Cancer — American Cancer Society
  6. Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation From Population-Based Cohort Studies — PLOS Medicine
  7. Endometrial Pathology in Breast Cancer Patients: Effect of Different Treatments on Ultrasonographic, Hysteroscopic and Histological Findings — Oncology Letters
  8. Hormone Therapy for Menopause Symptoms — Cleveland Clinic
  9. Menopausal Hormone Therapy and Cancer Risk — American Cancer Society
  10. Oral Contraceptives and Cancer Risk — National Cancer Institute
  11. Pregnancy Duration and Endometrial Cancer Risk: Nationwide Cohort Study — BMJ
  12. Infertility and Incident Endometrial Cancer Risk: A Pooled Analysis From the Epidemiology of Endometrial Cancer Consortium (E2C2) — British Journal of Cancer
  13. Use of Fertility Medications and Cancer Risk: A Review and Update — Current Opinion in Obstetrics & Gynecology
  14. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment — Journal of Clinical Oncology
  15. Body Mass Index — MedlinePlus
  16. The Effect of Diabetes on the Risk of Endometrial Cancer: An Updated a Systematic Review and Meta-Analysis — BMC Cancer
  17. Family History and Risk of Endometrial Cancer: A Systematic Review and Meta-Analysis — Obstetrics and Gynecology
  18. Endometrial Cancer and Lynch Syndrome: Clinical and Pathologic Considerations — Cancer Control
  19. Precancerous Conditions of the Uterus — Canadian Cancer Society

Posted on September 6, 2023
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Danielle Leonardo, M.D. is a board-certified specialist in internal medicine and medical oncology from the Philippines and has been practicing medicine since 2014. Learn more about her here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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