Uterine cancer, also known as endometrial cancer, is the most common type of gynecologic cancer in women. It begins in the lining of the uterus (the endometrium) and often develops when hormonal, genetic, or lifestyle factors disrupt the normal balance of cell growth.

While the disease can affect women of any age, some people are at significantly higher risk due to specific biological and environmental factors. Recognizing these risk groups is essential for prevention, early detection, and timely treatment.

Let’s explore who faces the greatest risk for uterine cancer — and why.

Hormonal Imbalance

One of the leading risk factors for uterine cancer is hormonal imbalance, particularly excess exposure to estrogen without enough progesterone.

Estrogen helps the uterine lining grow, while progesterone keeps that growth in check. When estrogen acts unopposed — meaning there isn’t enough progesterone to balance it — the lining can overgrow and eventually turn cancerous.

Situations linked to unopposed estrogen include:

  • Early menstruation (before age 12)

  • Late menopause (after age 55)

  • Irregular ovulation or lack of ovulation

  • Polycystic ovary syndrome (PCOS)

  • Estrogen-only hormone replacement therapy after menopause

Women exposed to high levels of estrogen for long periods face a much higher lifetime risk of developing uterine cancer.

Obesity and Body Weight

Obesity is one of the strongest risk factors for uterine cancer. Fat tissue converts other hormones into estrogen, leading to chronically elevated estrogen levels — even after menopause when the ovaries stop producing it.

Women who are overweight (BMI 25–29) have about 2 times the risk, while those with obesity (BMI 30 or higher) may face up to 3–4 times the risk compared to women with a healthy body weight.

In addition, obesity contributes to insulin resistance and chronic inflammation, both of which encourage abnormal cell growth and cancer development.

Maintaining a balanced diet and regular exercise are proven strategies to reduce this risk.

Age and Menopause

Uterine cancer primarily affects older women, particularly those who have reached menopause.

Most diagnoses occur between the ages of 50 and 70. This age range reflects the cumulative effect of hormonal exposure over decades.

After menopause, the body continues to produce small amounts of estrogen through fat tissue, and without the balancing effect of progesterone from menstrual cycles, the uterine lining may become vulnerable to abnormal changes.

That’s why postmenopausal bleeding — even a small amount — should always be evaluated by a doctor.

Reproductive History

A woman’s reproductive history influences her risk for uterine cancer because pregnancy and menstruation affect hormone levels.

Higher risk:

  • Never having been pregnant (nulliparity)

  • Infertility or conditions that prevent ovulation

Lower risk:

  • Having one or more full-term pregnancies

  • Using oral contraceptives (birth control pills)

During pregnancy, progesterone levels rise and estrogen levels are suppressed, which helps protect the uterine lining. Women who experience multiple pregnancies therefore have lower long-term risk.

Polycystic Ovary Syndrome (PCOS)

PCOS is a hormonal disorder that disrupts ovulation and causes irregular or absent periods. This leads to long-term estrogen exposure without progesterone — the same imbalance that drives uterine cancer development.

Women with PCOS often have additional metabolic problems such as insulin resistance, obesity, and type 2 diabetes, which further elevate their risk.

Regular monitoring, maintaining a healthy weight, and managing menstrual cycles with medical guidance can help reduce this risk significantly.

Diabetes and Insulin Resistance

Women with type 2 diabetes or metabolic syndrome face an increased risk of uterine cancer, even independent of obesity.

High insulin and glucose levels stimulate cell growth and inhibit programmed cell death (apoptosis), which can allow abnormal cells to survive and multiply.

The link between diabetes and uterine cancer underscores the importance of controlling blood sugar through diet, medication, and exercise.

Genetic Factors and Family History

Genetics also play an important role in determining uterine cancer risk.

Women with close relatives (mother, sister, or daughter) who have had uterine or colon cancer may carry inherited mutations that increase their susceptibility.

The most notable genetic condition associated with uterine cancer is Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

This syndrome is caused by mutations in DNA repair genes — including MLH1, MSH2, MSH6, and PMS2. Women with Lynch syndrome have up to a 60% lifetime risk of developing uterine cancer.

Genetic testing is recommended for anyone with a strong family cancer history.

Tamoxifen Use

Tamoxifen, a medication used to prevent and treat breast cancer, has a paradoxical effect.

While it blocks estrogen in breast tissue, it can act like estrogen in the uterus, stimulating the lining and increasing uterine cancer risk.

The risk is generally low and depends on:

  • The length of treatment (risk increases after 5 years of use)

  • The individual’s age and menopausal status

Women taking tamoxifen should undergo regular pelvic exams and report any unusual bleeding immediately.

Hormone Therapy After Menopause

Hormone replacement therapy (HRT) helps manage menopausal symptoms like hot flashes, but the type of hormone therapy matters.

  • Estrogen-only therapy increases uterine cancer risk.

  • Combined estrogen-progesterone therapy protects the uterus and lowers risk.

Women with a uterus should never use estrogen-only therapy without progesterone unless advised by a specialist. Regular monitoring ensures that hormone therapy remains safe and balanced.

Previous Radiation Therapy

Women who have received pelvic radiation therapy to treat another cancer (such as cervical or rectal cancer) have a slightly increased risk of developing uterine cancer later in life.

Radiation can damage DNA in nearby tissues, potentially causing mutations that lead to cancer years later.

The risk remains small, but these women should be closely monitored for any signs of abnormal uterine bleeding or changes.

Diet and Lifestyle Habits

Lifestyle choices have a profound impact on cancer risk. Certain habits can either protect or predispose you to uterine cancer.

Higher risk:

  • Diets high in saturated fats and red meats

  • Sedentary lifestyle

  • Heavy alcohol consumption

Lower risk:

  • Diets rich in fruits, vegetables, whole grains, and fiber

  • Regular physical activity

  • Avoiding smoking and excessive alcohol

Exercise reduces obesity, improves hormone balance, and lowers inflammation — all factors that help protect the uterus from cancer.

Ethnicity and Race

Research shows that Black women are more likely to develop aggressive forms of uterine cancer, such as non-endometrioid or serous carcinoma, compared to White women.

While the overall incidence of uterine cancer is higher in White women, mortality rates are nearly twice as high in Black women, often due to later-stage diagnosis and limited access to early screening.

These disparities highlight the urgent need for equitable healthcare access and awareness campaigns across all communities.

Medical Conditions That Increase Risk

Several medical conditions increase uterine cancer risk by altering hormone levels or causing chronic inflammation:

  • Hypertension (high blood pressure)

  • Thyroid disorders

  • Endometrial hyperplasia (thickening of the uterine lining, often precancerous)

Treating these conditions early and maintaining regular gynecologic checkups can significantly reduce long-term risk.

Endometrial Hyperplasia

Endometrial hyperplasia occurs when the uterine lining grows too thick due to excess estrogen stimulation.

There are four main types, but those with atypical cells — particularly atypical complex hyperplasia — are considered precancerous and can progress to uterine cancer if untreated.

Risk increases with age, obesity, and hormone imbalance. Treatment often involves progesterone therapy or, in high-risk cases, surgery to prevent malignancy.

Long-Term Health Conditions

Chronic inflammation, immune disorders, or exposure to environmental toxins may also increase uterine cancer risk.

For example:

  • Autoimmune diseases that affect hormonal balance

  • Exposure to endocrine disruptors such as BPA and pesticides

  • Chronic stress that disrupts immune regulation

While these factors are harder to quantify, maintaining an anti-inflammatory lifestyle — through diet, sleep, and stress reduction — supports long-term uterine health.

Protective Factors

While some risk factors can’t be changed, there are proven protective measures that reduce uterine cancer risk:

  • Using combined oral contraceptives for at least 5 years (protection can last up to 10 years after stopping)

  • Maintaining a healthy BMI

  • Managing blood sugar and insulin levels

  • Eating a plant-rich diet with antioxidants

  • Regular exercise to improve hormonal and metabolic balance

These proactive steps empower women to take control of their reproductive health.

When to See a Doctor

Early detection makes a tremendous difference. Seek medical advice if you experience:

  • Postmenopausal bleeding

  • Bleeding between periods

  • Pelvic or lower abdominal pain

  • Unusual vaginal discharge

Even if symptoms seem minor, prompt evaluation can catch problems early — often before cancer develops or spreads.

High-Risk Groups Summary

To summarize, you’re at higher risk for uterine cancer if you:

  • Are postmenopausal

  • Are overweight or obese

  • Have hormonal imbalances (especially high estrogen)

  • Have diabetes or PCOS

  • Have a family history of uterine or colon cancer

  • Have Lynch syndrome

  • Have taken estrogen-only hormone therapy or tamoxifen

  • Have undergone pelvic radiation

Understanding where you stand allows you to take preventive action and work closely with your doctor for screening and monitoring.

Prevention and Regular Screening

While there’s no universal screening test for uterine cancer, regular gynecologic exams remain essential.

Doctors may recommend:

  • Transvaginal ultrasound to monitor uterine thickness.

  • Endometrial biopsy if abnormal bleeding occurs.

  • Genetic counseling if hereditary cancer risk is suspected.

Early detection dramatically improves survival — particularly since Stage I uterine cancer has a cure rate of over 90%.

Conclusion

Uterine cancer risk is influenced by many factors — hormonal, genetic, metabolic, and lifestyle-related. Women who are postmenopausal, obese, diabetic, or have a family history of cancer face the highest risks.

However, risk is not destiny. By understanding personal risk factors and adopting a proactive approach — through healthy living, medical monitoring, and timely evaluation — many cases can be prevented or detected early, when treatment is most effective.

Empowering yourself with knowledge is the first step toward lifelong reproductive health.