Uterine cancer, also known as endometrial cancer, begins when the cells lining the uterus start growing uncontrollably. Understanding what causes this abnormal growth is crucial for early detection and prevention. While doctors can’t pinpoint a single cause, research has identified several risk factors and biological mechanisms that can lead to the development of uterine cancer.

Hormonal Imbalance

One of the leading causes of uterine cancer is an imbalance between the hormones estrogen and progesterone. Estrogen helps stimulate the growth of the uterine lining (endometrium), while progesterone counterbalances it by shedding the lining during menstruation. When estrogen levels remain high without enough progesterone — a condition known as “unopposed estrogen” — it can cause the cells in the uterus to grow excessively, increasing the risk of cancer.

This imbalance often occurs during:

  • Perimenopause or menopause

  • Hormone replacement therapy with estrogen alone

  • Polycystic ovary syndrome (PCOS)

  • Obesity, which raises estrogen levels through fat tissue production

Over time, continuous exposure to high estrogen levels can cause mutations in the endometrial cells, potentially turning them cancerous.

Genetic Mutations

Genetic factors play a significant role in the development of uterine cancer. Some individuals inherit mutations that increase their susceptibility to certain cancers. The most notable example is Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC). It’s caused by mutations in genes responsible for repairing DNA damage — such as MLH1, MSH2, MSH6, and PMS2.

When these genes fail to fix errors in the DNA, abnormal cells can accumulate and form tumors. Women with Lynch syndrome have a lifetime risk of developing uterine cancer of up to 60%, far higher than the general population.

Additionally, mutations in the PTEN gene (commonly seen in Cowden syndrome) and PIK3CA gene are also linked to endometrial cancer, highlighting the role of genetic predisposition in triggering abnormal cell growth.

Obesity and Metabolic Factors

Excess body fat doesn’t just change your appearance — it can alter your hormone levels and metabolism in ways that encourage cancer growth. Adipose tissue (body fat) converts androgens into estrogen, leading to elevated estrogen levels in postmenopausal women. This extra estrogen continuously stimulates the uterine lining, even when the ovaries no longer produce hormones.

Moreover, obesity is associated with insulin resistance and higher levels of insulin-like growth factors (IGFs). These compounds promote cell proliferation and inhibit apoptosis (cell death), creating an environment where abnormal cells can thrive. Studies show that women with a body mass index (BMI) over 30 are two to four times more likely to develop uterine cancer compared to women with a normal BMI.

Age and Menstrual History

The risk of uterine cancer increases with age, especially after menopause. Women over 50 are most commonly affected, but the seeds for risk are often planted much earlier in life.

Certain menstrual patterns also influence hormone exposure:

  • Early menstruation (before age 12)

  • Late menopause (after age 55)

  • Fewer or no pregnancies (nulliparity)

Each of these situations extends the total number of menstrual cycles a woman experiences, leading to prolonged estrogen exposure and, consequently, a higher risk of uterine cancer over time.

Diabetes and Insulin Resistance

Chronic high blood sugar doesn’t just affect the heart and kidneys — it also impacts cancer risk. Diabetes, particularly Type 2, is linked to uterine cancer through insulin resistance. Elevated insulin levels act like a growth factor, stimulating endometrial cells and preventing them from dying when they should.

Diabetic women are nearly twice as likely to develop uterine cancer as non-diabetic women. This risk remains significant even after accounting for obesity, suggesting that metabolic dysfunction plays an independent role in promoting cancerous changes in uterine tissue.

Use of Hormone Therapy and Birth Control

Hormone therapy can both increase and reduce the risk of uterine cancer, depending on the type and duration of use.

  • Estrogen-only therapy: When taken after menopause without progesterone, it significantly raises uterine cancer risk.

  • Combined estrogen-progesterone therapy: This combination helps protect the endometrium from excessive estrogen exposure.

  • Tamoxifen: A drug used to treat breast cancer can act like estrogen in the uterus, slightly increasing the risk when used for several years.

Interestingly, oral contraceptives (birth control pills containing both estrogen and progesterone) have the opposite effect — they reduce uterine cancer risk. The protective benefit can last for more than a decade after discontinuation.

Polycystic Ovary Syndrome (PCOS)

PCOS is a hormonal disorder that disrupts ovulation and leads to irregular or absent periods. Without regular shedding of the uterine lining, cells can accumulate and grow excessively under continuous estrogen stimulation. Over time, this may result in endometrial hyperplasia — a precancerous condition that can progress to uterine cancer if left untreated.

Women with PCOS are also more likely to be overweight and insulin resistant, further compounding their risk.

Diet and Nutrition

What you eat plays a subtle but powerful role in uterine cancer development. Diets high in saturated fats, refined sugars, and processed foods can promote obesity and insulin resistance, while low intake of fruits, vegetables, and fiber deprives the body of protective antioxidants.

Conversely, consuming foods rich in beta-carotene, vitamins C and E, and phytoestrogens (found in soy products) may help regulate hormone levels and protect against oxidative DNA damage.

Regular exercise, maintaining a healthy weight, and reducing sugar intake are all proven strategies to lower uterine cancer risk.

Previous Radiation Therapy

Women who have received pelvic radiation therapy to treat another cancer (such as cervical or rectal cancer) have a higher risk of developing uterine cancer later in life. Radiation can cause DNA damage in nearby tissues, sometimes leading to mutations years after the initial treatment.

While this risk remains relatively small, it emphasizes the importance of regular gynecological check-ups for women with a history of radiation exposure.

Endometrial Hyperplasia

Endometrial hyperplasia refers to the thickening of the uterine lining caused by excessive estrogen stimulation. It’s considered a precancerous condition, meaning it’s not yet cancer but has the potential to turn malignant if not treated.

There are four main types of hyperplasia:

  • Simple hyperplasia

  • Complex hyperplasia

  • Atypical simple hyperplasia

  • Atypical complex hyperplasia

The last two involve abnormal cell shapes and structures, significantly increasing cancer risk. Treating hyperplasia early with progesterone therapy or surgical options can prevent progression to uterine cancer.

Family and Reproductive History

Family history plays a major role in uterine cancer susceptibility. Having close relatives (mother, sister, or daughter) with uterine or colorectal cancer increases your risk, especially when coupled with hereditary syndromes like Lynch syndrome.

Reproductive patterns also matter. Women who have never been pregnant or who experienced infertility are at higher risk because they’ve had fewer breaks from estrogen exposure. Pregnancy naturally increases progesterone levels, which protect the uterine lining.

Lifestyle and Environmental Factors

Lifestyle choices can either fuel or fight cancer risk. Smoking and alcohol consumption have complex effects on hormone metabolism and immune function. While smoking appears to slightly lower estrogen levels, it introduces carcinogens that can damage DNA and trigger abnormal cell changes. Alcohol, on the other hand, increases circulating estrogen, adding to the cumulative hormonal burden.

Environmental toxins such as pesticides, industrial chemicals, and endocrine disruptors can also mimic estrogen and interfere with hormonal balance, subtly increasing cancer risk over time.

Immune System and Inflammation

Chronic inflammation is a silent trigger for many cancers, including uterine cancer. Inflammatory processes release cytokines and free radicals that can damage DNA and encourage abnormal cell proliferation.

Conditions like obesity, diabetes, and chronic infections can all contribute to persistent low-grade inflammation. Moreover, a weakened immune system may fail to recognize and destroy early cancer cells before they multiply.

How These Factors Interact

It’s rare for one single cause to trigger uterine cancer. Instead, multiple risk factors — hormonal, genetic, metabolic, and environmental — interact in complex ways. For example, an obese woman with diabetes and a family history of cancer faces compounded risks due to overlapping biological mechanisms.

Researchers emphasize that while you can’t change your genes or age, modifiable lifestyle factors such as weight control, diet, and regular exercise can dramatically lower your risk.

Preventive Measures

Preventing uterine cancer starts with awareness and proactive care:

  • Maintain a healthy weight through balanced nutrition and physical activity.

  • Manage conditions like diabetes and PCOS effectively.

  • Discuss hormone therapy options carefully with your doctor.

  • Use combined oral contraceptives for long-term hormonal balance if suitable.

  • Schedule regular pelvic exams and report any abnormal bleeding immediately.

Early detection through transvaginal ultrasound and endometrial biopsy can identify precancerous changes before they progress.

When to See a Doctor

Unusual vaginal bleeding, pelvic pain, or discharge after menopause should never be ignored. These are among the earliest warning signs of uterine cancer. Early diagnosis often leads to successful treatment and a favorable prognosis.

Conclusion

Uterine cancer arises from a complex mix of hormonal imbalance, genetic susceptibility, and lifestyle factors. While some risks are unavoidable, many can be controlled through mindful choices — maintaining a healthy weight, managing metabolic health, and staying alert to early symptoms. Understanding what triggers abnormal cell growth empowers women to take charge of their health and seek timely medical advice.