By Dr. Houssein El Hajj, gynecologic oncologist at Institut Gustave Roussy, France

 

[Editor’s Note: Because June is Uterine Cancer Awareness Month, our working group asked Dr. El Hajj to contribute this article for our blog. We are grateful to him for sharing his expertise!]

 

Understanding Endometrial Cancer Risk: The crucial role of maintaining a healthier body weight and beyond

 

Uterine cancer is the second most common gynecologic cancer worldwide when both high- and low-resource countries are considered. More than 90% of cases are endometrial cancers, which originate from the inner lining of the uterus. Endometrial cancer is most common in high-income countries, with Europe recording some of the highest rates of both new cases and deaths in 2020. In 2022, approximately 130,000 women across Europe were diagnosed with endometrial cancer, and nearly 30,000 deaths were attributed to the disease. Despite these figures, the outlook for women diagnosed with endometrial cancer in Europe remains encouraging: approximately 80% to 85% survive at least five years after diagnosis (1).

 

Endometrial cancer is hormone-dependent, meaning that any factor exposing the body to high or prolonged levels of estrogen can increase the risk. Among these, excess and metabolic health issues like diabetes are among the most important—and most preventable—risk factors.

 

[Editor’s note: As with many topics about our bodies, body weight is a sensitive topic in women’s health in many cultures. We recognize it often carries its own stigma and societal pressures. See below for Dr. El Hajj’s explanation of how ‘excess weight’ is medically defined.]

 

The main modifiable risk factor is body weight: an estimated 34% of endometrial cancer cases are attributable to being overweight or obese. Other recognized risks include certain genetic mutations and familial predispositions.

While metabolic health plays a significant role, other factors also contribute:

 

• Age: Risk increases after menopause, especially around 70 years old.
• Family history: Inherited genetic mutations, like Lynch syndrome, can raise the risk significantly.
• Hormonal factors: Early puberty, late menopause, having no children, and certain hormonal treatments (like estrogen-only menopause therapy) can increase exposure to estrogen and risk.
• Lifestyle factors: Lack of physical activity and poor diet are also associated with higher risk.
• Rare exposures: Use of tamoxifen (a breast cancer drug) or past exposure to diethylstilbestrol (DES) during pregnancy may slightly raise the risk.

 

The Impact of Weight-Related Factors on Endometrial Cancer Risk

 

Adipose tissue can affect the body’s hormonal and metabolic balance in ways that may increase the risk of endometrial cancer. Here's how.

 

Adipose tissue isn’t just a storage site—it actively produces estrogens, especially after menopause. In women with increased adipose mass, there's more conversion of certain hormones into estrone and estradiol (types of estrogen), which continuously stimulate the lining of the uterus. On top of that, these women tend to have lower levels of sex hormone-binding globulin (SHBG), which normally helps control hormone activity. Lower levels of this sex hormone-binding globulin mean more free estrogen circulating in the body—and more hormonal stimulation of the endometrium (2–4).

 

Being overweight could be associated with insulin resistance and changes in growth factors (like IGF-1), creating a biological environment that encourages cell growth—and potentially cancer.

 

Even women who are so-called “metabolically healthy” overweight (those who don’t have diabetes or high blood pressure) still appear to carry a higher risk of endometrial cancer compared to women with normal weight (5).

 

Weight Has a Heavy Impact

 

The relationship between body weight and cancer risk is well documented. A large analysis combining data from multiple studies in different countries and over 14,000 women with endometrial cancer showed that risk increases progressively with body mass index (BMI) (6):

 

• overweight (BMI 25–30) increases the risk by 1.5 times.
• Moderate obesity (BMI 30–35) doubles the risk.
• Severe obesity (BMI 35–40) quadruples the risk.
• Massive obesity (BMI over 40) increases the risk sevenfold.

 

This pattern holds true both for what was previously described as Type I endometrial cancer (the more common, hormone-driven type) and to a lesser extent for Type II (a more aggressive form).

 

Interestingly, obesity has also been linked to earlier onset of endometrial cancer, meaning cases that occur before age 45. (7).

A Complex Picture: Lower Grade, But Not Lower Risk

 

You might assume that higher BMI leads to more aggressive cancers—but the reality is more nuanced. Women with a BMI at or above 40 are more likely to be diagnosed at an earlier stage and with less aggressive (low-grade) tumors, particularly the endometrioid subtype. However, despite this, they often face higher mortality rates (8).

Why? Researchers believe it could be due to persistent hormonal stimulation or the combined impact of co-existing health conditions like diabetes and heart disease, which are more common in individuals with obesity.

 

How Can The Risk be Reduced?

 

The good news is that small, positive changes can make a big difference.

 

Studies have shown that women who intentionally lost weight had a 29–56% lower risk of endometrial cancer compared to those with stable weight (9,10). weight loss interventions effectively reduce inflammatory markers and hormones linked to endometrial cancer risk (11). Regular physical activity is associated with a decreased risk of developing endometrial cancer (12). When indicated, bariatric surgery is also associated with a 59% lower risk of endometrial cancer (13).

 

In addition to weight management, physical activity appears to play an important role in endometrial cancer survivorship. Higher levels of recreational physical activity, especially post-diagnosis, are associated with improved disease-free and overall survival in endometrial cancer survivors (14). Furthermore, physical activity correlates with better quality of life, improving both physical and psychological aspects.

 

Here are some steps that could help:

 

Move More, Feel Better—No Gym Required!

 

You don’t need fancy equipment or extra time — just a little creativity! Try these:

 

• Take the stairs. Skip the elevator to strengthen your legs!
• Walk at lunch. A 10-minute stroll is an instant refresh!
• Ditch the car. Metro or bus = more steps for you!
• Stretch it out. Your body will thank you!
• Talk & walk. Meetings or catch-ups? Walk and chat!
• Play with energy. Kids playing? Join in! It's cardio in disguise!
• Make it social. Move with friends, laugh more, stay motivated!
• Dance it up. Try the Irish Network for Gynaecological Oncology’s Dance for World GO Day by choreographer Jane Shortall, set to Boyzone’s Working My Way Back To You!  https://youtu.be/xXE6_whRTBQ?si=K-EW4JlgLJl37O6G
• Jump for June. June is Uterine Cancer Awareness Month. Join #Jump4June on social media and challenge two friends to do it too! https://igcs.org/jump4june/

REMEMBER: It's About Empowerment, Not Blame

 

It’s important to know that having risk factors doesn’t mean you will definitely develop cancer. And weight is only one piece of the puzzle. Rather than focusing on why, we encourage women to feel empowered to talk to their doctor about endometrial cancer risk and take steps to lower that risk. Every small step towards a healthier lifestyle is a step towards lower risk.

 

Awareness is the first step to action. By understanding the link between obesity and endometrial cancer, women can make informed choices to protect their health. Share information about endometrial cancer with your family, your friends, and your community—together, we can make a difference.

 

 

 

REFERENCES

 

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209–49.
2. Siiteri PK. Adipose tissue as a source of hormones. Am J Clin Nutr. 1987 Jan;45(1 Suppl):277–82.
3. Potischman N, Swanson CA, Siiteri P, Hoover RN. Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst. 1996 Jun 5;88(11):756–8.
4. Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I. Endometrial cancer. Lancet Lond Engl. 2005 Aug 6;366(9484):491–505.
5. Cao Z, Zheng X, Yang H, Li S, Xu F, Yang X, et al. Association of obesity status and metabolic syndrome with site-specific cancers: a population-based cohort study. Br J Cancer. 2020 Oct;123(8):1336–44.
6. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol Off J Am Soc Clin Oncol. 2013 Jul 10;31(20):2607–18.
7. Pellerin GP, Finan MA. Endometrial cancer in women 45 years of age or younger: a clinicopathological analysis. Am J Obstet Gynecol. 2005 Nov;193(5):1640–4.
8. Everett E, Tamimi H, Greer B, Swisher E, Paley P, Mandel L, et al. The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. Gynecol Oncol. 2003 Jul;90(1):150–7.
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11. Clontz AD, Gan E, Hursting SD, Bae-Jump VL. Effects of Weight Loss on Key Obesity-Related Biomarkers Linked to the Risk of Endometrial Cancer: A Systematic Review and Meta-Analysis. Cancers. 2024 Jun 11;16(12):2197.
12. Voskuil DW, Monninkhof EM, Elias SG, Vlems FA, van Leeuwen FE, Task Force Physical Activity and Cancer. Physical Activity and Endometrial Cancer Risk, a Systematic Review of Current Evidence. Cancer Epidemiol Biomarkers Prev. 2007 Apr 6;16(4):639–48.
13. Zhang X, Rhoades J, Caan BJ, Cohn DE, Salani R, Noria S, et al. Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis. Int J Gynecol Cancer. 2019 Nov 1;29(9):1361–71.
14. Friedenreich CM, Stone CR, Cheung WY, Hayes SC. Physical Activity and Mortality in Cancer Survivors: A Systematic Review and Meta-Analysis. JNCI Cancer Spectr. 2020 Feb 1;4(1):pkz080.