Español
Questions About Cancer? 1-800-4-CANCER
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Endometrial Cancer Prevention (PDQ®)

Table of Contents

Who is at Risk?

Endometrial cancer is a disease that primarily affects postmenopausal women at an average age of 60 years at diagnosis. Risk factors include postmenopausal estrogen therapy, obesity, a high-fat diet, reproductive factors like nulliparity, early menarche and late menopause, polycystic ovarian syndrome, and tamoxifen use. Women with hereditary nonpolyposis colorectal cancer syndrome have a markedly increased risk of endometrial cancer compared with women in the general population.

Overview

Note: Separate PDQ summaries on Endometrial Cancer Screening; Endometrial Cancer Treatment; and Uterine Sarcoma Treatment are also available.

Intervention Associated With Decreased Risk

Oral contraceptives

Based on solid evidence, at least 1 year’s use of oral contraceptives containing estrogen and progesterone decreases endometrial cancer risk, proportionate to duration of use. This benefit lasts at least 15 years after cessation.[1,2]

Magnitude of Effect: Use of oral contraceptives for 4 years reduced risk by 56%, 8 years by 67%, and 12 years by 72%.

  • Study Design: Case-control studies and prospective studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.
Harms

Based on solid evidence, current use of oral contraceptives is associated with an increased risk of blood clots, stroke, and myocardial infarction, especially among women who smoke cigarettes and who are older than 35 years.

  • Study Design: Randomized controlled clinical trials.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Physical activity

Based on solid evidence, increased physical exercise is associated with a decreased risk of endometrial cancer.[3-5]

Magnitude of Effect: Regular exercise may be associated with a 38% to 46% decrease in risk, although a trend in risk reduction with increasing duration or intensity has not been shown.

  • Study Design: Multiple cohort and case-control studies.
  • Internal Validity: Good.
  • Consistency: Fair.
  • External Validity: Good.

Factors Associated With Decreased Risk

Increasing parity and lactation

Based on solid evidence, increased parity and duration of lactation are associated with a decreased risk of endometrial cancer.[6,7]

Magnitude of Effect: Parous women have a 35% decreased risk of endometrial cancer (hazard ratio = 0.65; 95% confidence interval [CI], 0.54–0.77) compared with nulliparous women. Duration of breastfeeding has also been associated with a decreased risk, with a 23% risk reduction noted with breastfeeding more than 18 months. The risk reduction was attenuated when adjusted for parity.[8,9]

  • Study Design: Prospective cohort study.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Factors Associated With Increased Risk

Hormone therapy (HT)

Based on solid evidence, unopposed estrogen is associated with an increased risk of endometrial cancer.[10] This excess risk of endometrial cancer associated with postmenopausal unopposed estrogen therapy can be eliminated by adding progestin, but this is associated with an increased risk of breast cancer.[11,12]

Magnitude of Effect: The risk of endometrial cancer associated with unopposed estrogen use for 5 or more years is more than tenfold higher than nonhormone use. Addition of progesterone to estrogen negates this risk, but combined HT increases the risk of breast cancer, which is not observed with unopposed estrogen.

  • Study Design: Randomized controlled trials, cohort, and case-control studies.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.
Harms

Based on solid evidence, the combined use of estrogen and progestin are associated with an increased risk of breast cancer, heart disease, stroke, and thrombosis.[11,13,14] Based on solid evidence, unopposed estrogen is associated with an excess risk of stroke and thrombosis.[15]

Magnitude of Effect: Combined estrogen and progestin after a mean of 5 years of treatment: Approximately a 26% relative increase in incidence of invasive breast cancer; a 29% relative increase in cardiovascular heart disease; a 41% relative increase in stroke, associated with combined estrogen and progestin; and a 113% relative increase in pulmonary embolus.

Estrogen only after a mean follow-up of 6.8 years: Approximately a 39% relative increase in stroke and a 34% relative increase in pulmonary embolus. Risk of cardiovascular heart disease and breast cancer were nonstatistically significantly lower in the estrogen-treated group.

  • Study Design: Randomized placebo-controlled trials.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Selective estrogen receptor modifiers

Based on solid evidence, more than 2 years of tamoxifen use is associated with an increased risk of endometrial cancer.[16,17] A different selective estrogen receptor modifier, raloxifene, does not have this association.[18,19]

Magnitude of Effect: Women taking tamoxifen for more than 2 years have a 2.3-fold to 7.5-fold relative risk (RR) of endometrial cancer.

  • Study Design: Multiple randomized controlled trials.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Obesity

Based on solid evidence, being overweight or obese is associated with an increased risk of endometrial cancer.[20-22]

The risk of endometrial cancer increases 1.59-fold per 5 kg/m2 change in body mass.[23]

  • Study Design: Multiple randomized controlled trials.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Interventions of Unproven or Disproven Effect

Weight loss

The evidence is insufficient to conclude whether weight loss is associated with a decreased incidence of endometrial cancer. Based on one study, self-reported intentional weight loss during 3 age periods was not associated with a decrease in endometrial cancer incidence.[24]

Magnitude of Effects: RR of endometrial cancer for women who intentionally lost at least 20 lbs was 0.93 (95% CI, 0.6–1.44).

  • Study Design: Cohort study with retrospectively self-reported data.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

References

  1. Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. JAMA 257 (6): 796-800, 1987. [PUBMED Abstract]
  2. Weiderpass E, Adami HO, Baron JA, et al.: Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes Control 10 (4): 277-84, 1999. [PUBMED Abstract]
  3. Moradi T, Weiderpass E, Signorello LB, et al.: Physical activity and postmenopausal endometrial cancer risk (Sweden). Cancer Causes Control 11 (9): 829-37, 2000. [PUBMED Abstract]
  4. Schouten LJ, Goldbohm RA, van den Brandt PA: Anthropometry, physical activity, and endometrial cancer risk: results from the Netherlands Cohort Study. J Natl Cancer Inst 96 (21): 1635-8, 2004. [PUBMED Abstract]
  5. Terry P, Baron JA, Weiderpass E, et al.: Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 82 (1): 38-42, 1999. [PUBMED Abstract]
  6. Newcomb PA, Trentham-Dietz A: Breast feeding practices in relation to endometrial cancer risk, USA. Cancer Causes Control 11 (7): 663-7, 2000. [PUBMED Abstract]
  7. Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, et al.: Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res 59 (15): 3658-62, 1999. [PUBMED Abstract]
  8. Dossus L, Allen N, Kaaks R, et al.: Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 127 (2): 442-51, 2010. [PUBMED Abstract]
  9. Karageorgi S, Hankinson SE, Kraft P, et al.: Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976-2004. Int J Cancer 126 (1): 208-16, 2010. [PUBMED Abstract]
  10. Shapiro S, Kelly JP, Rosenberg L, et al.: Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 313 (16): 969-72, 1985. [PUBMED Abstract]
  11. Anderson GL, Judd HL, Kaunitz AM, et al.: Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 290 (13): 1739-48, 2003. [PUBMED Abstract]
  12. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 275 (5): 370-5, 1996. [PUBMED Abstract]
  13. Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 288 (3): 321-33, 2002. [PUBMED Abstract]
  14. Persson I, Weiderpass E, Bergkvist L, et al.: Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Cancer Causes Control 10 (4): 253-60, 1999. [PUBMED Abstract]
  15. Anderson GL, Limacher M, Assaf AR, et al.: Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 291 (14): 1701-12, 2004. [PUBMED Abstract]
  16. Fisher B, Costantino JP, Redmond CK, et al.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86 (7): 527-37, 1994. [PUBMED Abstract]
  17. Fornander T, Rutqvist LE, Cedermark B, et al.: Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1 (8630): 117-20, 1989. [PUBMED Abstract]
  18. DeMichele A, Troxel AB, Berlin JA, et al.: Impact of raloxifene or tamoxifen use on endometrial cancer risk: a population-based case-control study. J Clin Oncol 26 (25): 4151-9, 2008. [PUBMED Abstract]
  19. Cummings SR, Eckert S, Krueger KA, et al.: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281 (23): 2189-97, 1999. [PUBMED Abstract]
  20. Bergström A, Pisani P, Tenet V, et al.: Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91 (3): 421-30, 2001. [PUBMED Abstract]
  21. Weiderpass E, Persson I, Adami HO, et al.: Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden). Cancer Causes Control 11 (2): 185-92, 2000. [PUBMED Abstract]
  22. Olson SH, Trevisan M, Marshall JR, et al.: Body mass index, weight gain, and risk of endometrial cancer. Nutr Cancer 23 (2): 141-9, 1995. [PUBMED Abstract]
  23. Renehan AG, Tyson M, Egger M, et al.: Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371 (9612): 569-78, 2008. [PUBMED Abstract]
  24. Parker ED, Folsom AR: Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study. Int J Obes Relat Metab Disord 27 (12): 1447-52, 2003. [PUBMED Abstract]

Description of Evidence

Background

Incidence and mortality

Endometrial cancer is the most common invasive gynecologic cancer in U.S. women, with an estimated 52,630 new cases expected to occur in 2014.[1] This disease primarily affects postmenopausal women at an average age of 60 years at diagnosis.[2] In the United States, it is estimated that approximately 8,590 women will die of endometrial cancer in 2014. From 2006 to 2010, incidence rates of endometrial cancer increased by 1.5% per year in women younger than 50 years and increased by 2.6% per year in women aged 50 years and older. During that same time, death rates from endometrial cancer increased by 1.5% per year in women younger than 50 years and remained stable in women aged 50 years and older.[1]

In the mid-1970s, the diagnosis of approximately 15,000 cases of postmenopausal endometrial cancers in excess of those expected on the basis of the underlying secular trend, has been related to the use of postmenopausal estrogen therapy.[3] Additional risk factors may be related to estrogenic effects, including obesity, a high-fat diet, polycystic ovarian syndrome, tamoxifen use and reproductive factors such as nulliparity, early menarche, and late menopause.

Women with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome have a markedly increased risk of endometrial cancer compared with women in the general population. Among women who are HNPCC mutation carriers, the estimated cumulative incidence of endometrial cancer ranges from 20% to 60%.[4,5]

Compared with white Americans, endometrial cancer incidence is lower in Japanese Americans (relative risk [RR] = 0.6; 95% confidence interval [CI], 0.46–0.83) and in Latinas (RR = 0.63; 95% CI, 0.46–0.87), but not in African Americans (RR = 0.76; 95% CI, 0.53–1.08) or in native Hawaiians (RR = 0.92; 95% CI, 0.58–1.46).[6] Higher mortality from endometrial cancer in African Americans is at least partly attributable to lower socioeconomic issues that impair access to care.[7]

Factors that have been associated with a decreased incidence of endometrial cancer include parity, lactation, use of combined oral contraceptives, a diet low in fat and high in plant foods, and physical activity.

Interventions Associated With Decreased Risk

Oral contraceptives

Use of combination oral contraceptives (COC) for at least 1 year reduces endometrial cancer risk by approximately 40%, as demonstrated by case-control studies and prospective cohort studies.[8-10] This decrease in risk persists for at least 15 years after discontinuation of COCs. A meta-analysis of ten case-control studies and one prospective study found an association between risk reduction and duration of use. Overall, 4 years of COC use was associated with a risk reduction of approximately 56%; 8 years, 67%; and 12 years, 72%. The single-prospective study did not show a duration response, but the risk was reduced by 80% after 9 years of follow-up.[11]

A Swedish population-based case-control study confirms these findings. Women who used any type of oral contraceptive had a 30% risk reduction (odds ratio [OR] = 0.7; 95% CI, 0.5–0.9) and women who used progestin-only pills had a 60% risk reduction (OR = 0.4; 95% CI, 0.2–1.4). Women who used COCs for at least 3 years had a 50% risk reduction (OR = 0.5; 95% CI, 0.3–0.7) and those who used COCs for at least 10 years had an 80% risk reduction (OR = 0.2; 95% CI, 0.1–0.4). Overall, risk decreased by 10% per year of COC use and was observed for atypical hyperplasias as well as all grades of invasive tumors.[12]

Physical activity

Several cohort [13,14] and case-control [15-23] studies of physical activity and endometrial cancer reveal a weak to moderate inverse relationship, despite varying methods of assessing physical activity levels. For postmenopausal women enrolled in The Netherlands Cohort Study on Diet and Cancer, a 46% reduction (RR = 0.54; 95% CI, 0.34–0.85; P = .002) in risk of endometrial cancer was reported in those women who were physically active 90 minutes or more per day compared with less than 30 minutes each day.[24] One case-control study of 822 endometrial cancer cases and 1,111 population controls showed that regular exercise was associated with a 38% decrease in risk (OR = 0.62; 95% CI, 0.51–0.76) without a trend for increasing duration or intensity of physical activity.[25] The Breast Cancer Detection Project Follow-up Study, using a prospective cohort, did not confirm an association between recent physical activity levels and risk.[26] It is unknown whether physical activity reduces endometrial cancer risk by reducing obesity, by reducing serum estrone levels, or by another mechanism.[27]

Factors Associated With Decreased Risk

Increasing parity and lactation

Decreased risk of endometrial cancer is associated with parity and lactation, perhaps by inhibiting ovulation. A case-control study conducted in Mexico City, among low-risk women, indicates a 58% to 72% reduction in risk of endometrial cancer associated with increasing duration of lactation. A significant trend was seen for duration of lactation and for the number of children breastfed.[28] A population-based case-control study, comparing Wisconsin women who breastfed for at least 2 weeks versus those who did not, was negative (OR = 0.90; 95% CI, 0.72–1.13). Increasing duration of lactation was not associated with a decrease in disease risk, but breastfeeding within the past three decades was associated with reduced risk (OR = 0.58; 95% CI, 0.36–0.96), as was the first breastfeeding after age 30 years (95% CI, 0.28–0.90).[29] The European Prospective Investigation into Cancer and Nutrition observed a decreased risk associated with parity compared with nulliparous women (hazard ratio = 0.65; 95% CI, 0.54–0.77) with a trend of decreasing risk with increasing number of full-term pregnancies (P < .0001). While breastfeeding for more than 18 months was associated with a decreased risk, the association attenuated and was no longer statistically significant after adjusting for the numbers of full-term pregnancies.[30]

Factors Associated With Increased Risk

Endogenous estrogen

Reproductive factors resulting in increased duration of exposure to endogenous estrogen, such as early menarche, nulliparity, and late menopause, are associated with an increased risk of endometrial cancer. Other factors associated with increased risk, such as obesity and polycystic ovary syndrome, may also be related to increased estrogen exposure.

The first prospective investigation of endogenous estrogens and the risk of endometrial cancer was a case-control study nested within the New York University Women’s Health Study.[31] Results suggest an increased risk of endometrial cancer associated with postmenopausal levels of endogenous hormones including estradiol, percent-free estradiol, and estrone. Conversely, risk was decreased with higher levels of percent sex hormone-binding globulin (SHBG)-bound estradiol and SHBG. Analyses conducted prior to adjustment for hormone levels indicated a positive association with body mass index (BMI). After adjustment for estrone level, the positive association of BMI with risk of endometrial cancer was attenuated, suggesting that hormone levels may be an intermediate effect of body weight.[32]

Exogenous estrogen

Postmenopausal hormone therapy (HT)

An association between estrogen replacement therapy and endometrial cancer was reported in 1975 [33] and confirmed soon after.[34,35] In these three studies, the overall risk ratio ranged from 4.5 to 8.0. Further studies documented an association with duration of use (10-fold to 30-fold with 5 years or more of use),[36-39] and a persistent effect lasting more than 10 years after 1 year’s use.[40] When these findings were publicized, prescriptions for estrogen declined sharply, followed rapidly by a drop in endometrial cancer incidence.[41]

Combination estrogen-progestin replacement therapy

Postmenopausal estrogen was long recognized to be associated with the risk of adenomatous hyperplasia, often a precursor of endometrial cancer.[42] In addition, progestational agents were known to be effective in the treatment of uterine neoplasms.[43-45] Consequently, improved postmenopausal HT was proposed, combining estrogen and progestin, so as to avoid the endometrial cancer risk associated with unopposed estrogen.[46,47]

The Postmenopausal Estrogen Progestin Interventions Trial [48] enrolled nearly 600 participants in a 3-year multicenter, double-blind, placebo-controlled trial. Five arms consisted of placebo, daily conjugated equine estrogen (CEE), CEE with progestin (medroxyprogesterone acetate [MPA] for 12 days of a 28-day cycle), CEE with micronized progesterone (MP) for 12 days of a 28-day cycle, or CEE with daily MP. Endometrial biopsies were obtained at baseline, annually, and as clinically indicated. Women on CEE had more pathologic abnormalities than women on placebo (simple hyperplasia: 27.7% vs. 0.8%, adenomatous hyperplasia: 22.7% vs. 0.8%, and atypical hyperplasia: 11.8% vs. 0%, respectively), but women on CEE with progestin did not.

A prospective cohort study was conducted among Swedish women for whom HTs were prescribed. For women using medium-potency unopposed estrogens for 6 years or more, the RR of invasive endometrial cancer was 4.2 (95% CI, 2.5–8.4) while the risk for women using a progestin-combined treatment for the same length of time was unaffected (RR = 1.4; 95% CI, 0.6–3.3).[49]

Selective estrogen receptor modulators (SERM): Tamoxifen and raloxifene

Tamoxifen and raloxifene are SERMs, drugs that have divergent estrogen agonist and antagonist effects in different target organs. The association between endometrial cancer and tamoxifen was first recognized in 1985, when three cases of endometrial cancer were described in women who had been treated with tamoxifen for breast cancer.[50] Since then, confirmation of the association has been provided by randomized clinical trials using tamoxifen for breast cancer treatment and prevention [51-54] and by case-control, observational, and laboratory studies.

The National Surgical Adjuvant Breast and Bowel Project, Breast Cancer Prevention Trial P-1 Study in women at high risk of invasive breast cancer demonstrated that tamoxifen decreased breast cancer incidence by 49%, but confirmed an increased incidence of endometrial cancer. The annual rate was 2.3 per 1,000 for women receiving tamoxifen versus 0.91 for those on placebo. Women older than 50 years experienced the largest effect. Of the 51 invasive cancers diagnosed in this trial, 50 were stage I.[55]

Raloxifene is a second-generation SERM approved for prophylaxis against postmenopausal osteoporosis. Unlike tamoxifen, it does not have an estrogenic effect on the uterus. The Multiple Outcomes of Raloxifene randomized trial, after 40 months of follow-up, showed that raloxifene reduced the risk of estrogen receptor–positive breast cancer, without increasing endometrial cancer (RR = 0.8; 95% CI, 0.2–2.7).[56] A population-based study of 547 women with endometrial cancer and 1,410 controls was done in Philadelphia, Pennsylvania. Of the cases, 18 (3.3%) had taken raloxifene and 34 (6.2%) had taken tamoxifen (OR = 3.0; 95% CI, 1.3–6.9).[57]

Obesity

Elevated BMI and obesity are associated with an increased risk of endometrial cancer. One of the possible mechanisms for the observed association is an increased level of serum estrone in obese women as a result of aromatization of androstenedione in adipose tissue, which increases the production of estrogen.[58] Alternatively, obesity has been associated with a reduction in levels of SHBG, which may protect against endometrial cancer by decreasing bioavailable estrogen.[59] Obesity has been associated with several factors known to increase the risk of endometrial cancer, including upper-body or central adiposity, polycystic ovarian syndrome, physical inactivity, and a diet high in saturated fat.[60]

Presumably, body weight is a modifiable risk factor, which accounts for a substantial proportion of endometrial cases worldwide. A study conducted among European countries estimated that between 26% and 47% of endometrial cancer cases can be attributed to overweight and obesity. The same group conducted a meta-analysis of 12 studies (5 cohort and 7 case-control), which examined the relationship between obesity and endometrial cancer. Eleven of the 12 studies concluded that there is a positive association between endometrial cancer and excess weight.[61]

RRs associated with obesity range from 2 to 10. Some studies show that upper-body and central weight confer a higher risk than peripheral body weight, even after consideration of BMI.[62-64] However, other studies have failed to confirm such an association. Several studies have observed a stronger association between endometrial cancer and obesity near the time of diagnosis compared with obesity earlier in life.[65-68]

Increasing age

Endometrial cancer primarily affects postmenopausal women, with a median age at diagnosis of 60 years.[2]

Genetic predisposition

Women with inherited conditions such as Lynch syndrome, Cowden syndrome, and polycystic ovary syndrome have an increased risk of endometrial cancer. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers and Genetics of Colorectal Cancer for more information.)

Interventions of Unproven or Disproven Effect on Risk

Weight loss

While it is known that obesity is associated with increased endometrial cancer risk, only one study examines the potential benefit of intentional weight loss. In the Iowa Women’s Health Study of 21,707 postmenopausal women,[69] participants completed a self-report questionnaire, about intentional weight loss between ages 18 and 39 years, between ages 40 and 54 years, and after age 55 years. Multivariate models adjusting for age, BMI, and BMI2 found no association between endometrial cancer incidence and intentional weight loss of at least 20 lbs (RR = 0.93; 95% CI, 0.60–1.44). The obvious limitation of this study is the reliance on retrospective self-reported data.[69]

Fruits, vegetables, and vitamins

The association between dietary factors, particularly fruit and vegetable intake, and endometrial cancer has been evaluated primarily in case-control studies. A systematic review of the evidence was undertaken as part of the World Cancer Research Fund’s Food, Nutrition, Physical Activity and Cancer: A Global Perspective (2006) report. A pooled OR from ten case-control studies for high versus low vegetable intake was 0.71 (95% CI, 0.55–0.91).[70] This association was similar to that reported previously in a report for the International Agency for Research on Cancer,[71] which was based on results from five case-control studies. Neither report observed evidence of an association between fruit intake and endometrial cancer.

There is case-control evidence suggesting that regular consumption of soy products reduces the risk of endometrial cancer.[72,73]

A consortium of seven prospective cohort studies examined the association between serum vitamin D levels and the development of endometrial cancer. After controlling for BMI, there was no evidence of an association between circulating vitamin D and risk of endometrial cancer.[74]

Multivitamin use has little or no influence on the risk of common cancers, including endometrial cancer, or on total mortality in postmenopausal women.[75]

References

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed November 24, 2014.
  2. American Cancer Society: Detailed Guide: Endometrial Cancer: What are the Risk Factors for Endometrial Cancer? Atlanta, Ga: American Cancer Society, 2005. Available online. Last accessed December 3, 2014.
  3. Jick H, Walker AM, Rothman KJ: The epidemic of endometrial cancer: a commentary. Am J Public Health 70 (3): 264-7, 1980. [PUBMED Abstract]
  4. Watson P, Vasen HF, Mecklin JP, et al.: The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer. Am J Med 96 (6): 516-20, 1994. [PUBMED Abstract]
  5. Aarnio M, Mecklin JP, Aaltonen LA, et al.: Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64 (6): 430-3, 1995. [PUBMED Abstract]
  6. Setiawan VW, Pike MC, Kolonel LN, et al.: Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study. Am J Epidemiol 165 (3): 262-70, 2007. [PUBMED Abstract]
  7. Madison T, Schottenfeld D, James SA, et al.: Endometrial cancer: socioeconomic status and racial/ethnic differences in stage at diagnosis, treatment, and survival. Am J Public Health 94 (12): 2104-11, 2004. [PUBMED Abstract]
  8. Combination oral contraceptive use and the risk of endometrial cancer. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. JAMA 257 (6): 796-800, 1987. [PUBMED Abstract]
  9. Ramcharan S, Pellegrin FA, Ray R, et al.: The Walnut Creek Contraceptive Drug Study: A Prospective Study of the Side Effects of Oral Contraceptives. Vol 3. Bethesda, Md: US Government Printing Office, 1981, NIH Pub. No 81-564.
  10. Beral V, Hannaford P, Kay C: Oral contraceptive use and malignancies of the genital tract. Results from the Royal College of General Practitioners' Oral Contraception Study. Lancet 2 (8624): 1331-5, 1988. [PUBMED Abstract]
  11. Schlesselman JJ: Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner's guide to meta-analysis. Hum Reprod 12 (9): 1851-63, 1997. [PUBMED Abstract]
  12. Weiderpass E, Adami HO, Baron JA, et al.: Use of oral contraceptives and endometrial cancer risk (Sweden). Cancer Causes Control 10 (4): 277-84, 1999. [PUBMED Abstract]
  13. Moradi T, Nyrén O, Bergström R, et al.: Risk for endometrial cancer in relation to occupational physical activity: a nationwide cohort study in Sweden. Int J Cancer 76 (5): 665-70, 1998. [PUBMED Abstract]
  14. Terry P, Baron JA, Weiderpass E, et al.: Lifestyle and endometrial cancer risk: a cohort study from the Swedish Twin Registry. Int J Cancer 82 (1): 38-42, 1999. [PUBMED Abstract]
  15. Goodman MT, Hankin JH, Wilkens LR, et al.: Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res 57 (22): 5077-85, 1997. [PUBMED Abstract]
  16. Hirose K, Tajima K, Hamajima N, et al.: Subsite (cervix/endometrium)-specific risk and protective factors in uterus cancer. Jpn J Cancer Res 87 (9): 1001-9, 1996. [PUBMED Abstract]
  17. Kalandidi A, Tzonou A, Lipworth L, et al.: A case-control study of endometrial cancer in relation to reproductive, somatometric, and life-style variables. Oncology 53 (5): 354-9, 1996 Sep-Oct. [PUBMED Abstract]
  18. Levi F, La Vecchia C, Negri E, et al.: Selected physical activities and the risk of endometrial cancer. Br J Cancer 67 (4): 846-51, 1993. [PUBMED Abstract]
  19. Moradi T, Weiderpass E, Signorello LB, et al.: Physical activity and postmenopausal endometrial cancer risk (Sweden). Cancer Causes Control 11 (9): 829-37, 2000. [PUBMED Abstract]
  20. Olson SH, Vena JE, Dorn JP, et al.: Exercise, occupational activity, and risk of endometrial cancer. Ann Epidemiol 7 (1): 46-53, 1997. [PUBMED Abstract]
  21. Shu XO, Hatch MC, Zheng W, et al.: Physical activity and risk of endometrial cancer. Epidemiology 4 (4): 342-9, 1993. [PUBMED Abstract]
  22. Sturgeon SR, Brinton LA, Berman ML, et al.: Past and present physical activity and endometrial cancer risk. Br J Cancer 68 (3): 584-9, 1993. [PUBMED Abstract]
  23. Zheng W, Shu XO, McLaughlin JK, et al.: Occupational physical activity and the incidence of cancer of the breast, corpus uteri, and ovary in Shanghai. Cancer 71 (11): 3620-4, 1993. [PUBMED Abstract]
  24. Schouten LJ, Goldbohm RA, van den Brandt PA: Anthropometry, physical activity, and endometrial cancer risk: results from the Netherlands Cohort Study. J Natl Cancer Inst 96 (21): 1635-8, 2004. [PUBMED Abstract]
  25. Littman AJ, Voigt LF, Beresford SA, et al.: Recreational physical activity and endometrial cancer risk. Am J Epidemiol 154 (10): 924-33, 2001. [PUBMED Abstract]
  26. Colbert LH, Lacey JV Jr, Schairer C, et al.: Physical activity and risk of endometrial cancer in a prospective cohort study (United States). Cancer Causes Control 14 (6): 559-67, 2003. [PUBMED Abstract]
  27. Cauley JA, Gutai JP, Kuller LH, et al.: The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol 129 (6): 1120-31, 1989. [PUBMED Abstract]
  28. Salazar-Martinez E, Lazcano-Ponce EC, Gonzalez Lira-Lira G, et al.: Reproductive factors of ovarian and endometrial cancer risk in a high fertility population in Mexico. Cancer Res 59 (15): 3658-62, 1999. [PUBMED Abstract]
  29. Newcomb PA, Trentham-Dietz A: Breast feeding practices in relation to endometrial cancer risk, USA. Cancer Causes Control 11 (7): 663-7, 2000. [PUBMED Abstract]
  30. Dossus L, Allen N, Kaaks R, et al.: Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 127 (2): 442-51, 2010. [PUBMED Abstract]
  31. Zeleniuch-Jacquotte A, Akhmedkhanov A, Kato I, et al.: Postmenopausal endogenous oestrogens and risk of endometrial cancer: results of a prospective study. Br J Cancer 84 (7): 975-81, 2001. [PUBMED Abstract]
  32. Lukanova A, Lundin E, Micheli A, et al.: Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 108 (3): 425-32, 2004. [PUBMED Abstract]
  33. Smith DC, Prentice R, Thompson DJ, et al.: Association of exogenous estrogen and endometrial carcinoma. N Engl J Med 293 (23): 1164-7, 1975. [PUBMED Abstract]
  34. Mack TM, Pike MC, Henderson BE, et al.: Estrogens and endometrial cancer in a retirement community. N Engl J Med 294 (23): 1262-7, 1976. [PUBMED Abstract]
  35. Ziel HK, Finkle WD: Increased risk of endometrial carcinoma among users of conjugated estrogens. N Engl J Med 293 (23): 1167-70, 1975. [PUBMED Abstract]
  36. Walker AM, Jick H: Cancer of the corpus uteri: increasing incidence in the United States, 1970--1975. Am J Epidemiol 110 (1): 47-51, 1979. [PUBMED Abstract]
  37. Gray LA Sr, Christopherson WM, Hoover RN: Estrogens and endometrial carcinoma. Obstet Gynecol 49 (4): 385-9, 1977. [PUBMED Abstract]
  38. McDonald TW, Annegers JF, O'Fallon WM, et al.: Exogenous estrogen and endometrial carcinoma: case-control and incidence study. Am J Obstet Gynecol 127 (6): 572-80, 1977. [PUBMED Abstract]
  39. Antunes CM, Strolley PD, Rosenshein NB, et al.: Endometrial cancer and estrogen use. Report of a large case-control study. N Engl J Med 300 (1): 9-13, 1979. [PUBMED Abstract]
  40. Shapiro S, Kelly JP, Rosenberg L, et al.: Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med 313 (16): 969-72, 1985. [PUBMED Abstract]
  41. Austin DF, Roe KM: The decreasing incidence of endometrial cancer: public health implications. Am J Public Health 72 (1): 65-8, 1982. [PUBMED Abstract]
  42. Gusberg SB: Precursors of corpus carcinoma estrogens and adenomatous hyperplasia. Am J Obstet Gynecol 54(6): 905-927, 1947.
  43. Gusberg SB: Hormone-dependence of endometrial cancer. Obstet Gynecol 30 (2): 287-93, 1967. [PUBMED Abstract]
  44. Bonte J: Medroxyprogesterone in the management of primary and recurrent or metastatic uterine adenocarcinoma. Acta Obstet Gynecol Scand Suppl 19: 21-4, 1972. [PUBMED Abstract]
  45. KISTNER RW: Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium. Cancer 12: 1106-22, 1959 Nov-Dec. [PUBMED Abstract]
  46. Whitehead MI: The effects of oestrogens and progestogens on the postmenopausal endometrium. Maturitas 1 (2): 87-98, 1978. [PUBMED Abstract]
  47. Hammond CB, Jelovsek FR, Lee KL, et al.: Effects of long-term estrogen replacement therapy. II. Neoplasia. Am J Obstet Gynecol 133 (5): 537-47, 1979. [PUBMED Abstract]
  48. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 275 (5): 370-5, 1996. [PUBMED Abstract]
  49. Persson I, Weiderpass E, Bergkvist L, et al.: Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Cancer Causes Control 10 (4): 253-60, 1999. [PUBMED Abstract]
  50. Killackey MA, Hakes TB, Pierce VK: Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treat Rep 69 (2): 237-8, 1985. [PUBMED Abstract]
  51. Fornander T, Rutqvist LE, Cedermark B, et al.: Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1 (8630): 117-20, 1989. [PUBMED Abstract]
  52. Rutqvist LE, Mattsson A: Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockholm Breast Cancer Study Group. J Natl Cancer Inst 85 (17): 1398-406, 1993. [PUBMED Abstract]
  53. Andersson M, Storm HH, Mouridsen HT: Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer. J Natl Cancer Inst 83 (14): 1013-7, 1991. [PUBMED Abstract]
  54. Fisher B, Costantino JP, Redmond CK, et al.: Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst 86 (7): 527-37, 1994. [PUBMED Abstract]
  55. Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90 (18): 1371-88, 1998. [PUBMED Abstract]
  56. Cummings SR, Eckert S, Krueger KA, et al.: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281 (23): 2189-97, 1999. [PUBMED Abstract]
  57. DeMichele A, Troxel AB, Berlin JA, et al.: Impact of raloxifene or tamoxifen use on endometrial cancer risk: a population-based case-control study. J Clin Oncol 26 (25): 4151-9, 2008. [PUBMED Abstract]
  58. Enriori CL, Reforzo-Membrives J: Peripheral aromatization as a risk factor for breast and endometrial cancer in postmenopausal women: a review. Gynecol Oncol 17 (1): 1-21, 1984. [PUBMED Abstract]
  59. Davidson BJ, Gambone JC, Lagasse LD, et al.: Free estradiol in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 52 (3): 404-8, 1981. [PUBMED Abstract]
  60. Troisi R, Potischman N, Hoover RN, et al.: Insulin and endometrial cancer. Am J Epidemiol 146 (6): 476-82, 1997. [PUBMED Abstract]
  61. Bergström A, Pisani P, Tenet V, et al.: Overweight as an avoidable cause of cancer in Europe. Int J Cancer 91 (3): 421-30, 2001. [PUBMED Abstract]
  62. Swanson CA, Potischman N, Wilbanks GD, et al.: Relation of endometrial cancer risk to past and contemporary body size and body fat distribution. Cancer Epidemiol Biomarkers Prev 2 (4): 321-7, 1993 Jul-Aug. [PUBMED Abstract]
  63. Elliott EA, Matanoski GM, Rosenshein NB, et al.: Body fat patterning in women with endometrial cancer. Gynecol Oncol 39 (3): 253-8, 1990. [PUBMED Abstract]
  64. Schapira DV, Kumar NB, Lyman GH, et al.: Upper-body fat distribution and endometrial cancer risk. JAMA 266 (13): 1808-11, 1991. [PUBMED Abstract]
  65. Olson SH, Trevisan M, Marshall JR, et al.: Body mass index, weight gain, and risk of endometrial cancer. Nutr Cancer 23 (2): 141-9, 1995. [PUBMED Abstract]
  66. Weiderpass E, Persson I, Adami HO, et al.: Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden). Cancer Causes Control 11 (2): 185-92, 2000. [PUBMED Abstract]
  67. Le Marchand L, Wilkens LR, Mi MP: Early-age body size, adult weight gain and endometrial cancer risk. Int J Cancer 48 (6): 807-11, 1991. [PUBMED Abstract]
  68. Shu XO, Brinton LA, Zheng W, et al.: Relation of obesity and body fat distribution to endometrial cancer in Shanghai, China. Cancer Res 52 (14): 3865-70, 1992. [PUBMED Abstract]
  69. Parker ED, Folsom AR: Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study. Int J Obes Relat Metab Disord 27 (12): 1447-52, 2003. [PUBMED Abstract]
  70. International Agency for Research On Cancer: IARC Handbooks of Cancer Prevention. Volume 8: Fruit and Vegetables. Lyon, France: International Agency for Research On Cancer, 2003.
  71. Bandera EV, Kushi LH, Gifkins DM, et al.: WCRF Systematic Literature Review: The Association Between Food, Nutrition, and Physical Activity and the Risk of Endometrial Cancer and Underlying Mechanisms. Washington, DC: World Cancer Research Fund, American Institute for Cancer Research, 2006.
  72. Horn-Ross PL, John EM, Canchola AJ, et al.: Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 95 (15): 1158-64, 2003. [PUBMED Abstract]
  73. Xu WH, Zheng W, Xiang YB, et al.: Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study. BMJ 328 (7451): 1285, 2004. [PUBMED Abstract]
  74. Zeleniuch-Jacquotte A, Gallicchio L, Hartmuller V, et al.: Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol 172 (1): 36-46, 2010. [PUBMED Abstract]
  75. Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al.: Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts. Arch Intern Med 169 (3): 294-304, 2009. [PUBMED Abstract]

Changes to This Summary (12/05/2014)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

Questions or Comments About This Summary

If you have questions or comments about this summary, please send them to Cancer.gov through the Web site’s Contact Form. We can respond only to email messages written in English.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about endometrial cancer prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

The preferred citation for this PDQ summary is:

National Cancer Institute: PDQ® Endometrial Cancer Prevention. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/prevention/endometrial/HealthProfessional. Accessed <MM/DD/YYYY>.

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.

Get More Information From NCI

Call 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

  • NCI Public Inquiries Office
  • 9609 Medical Center Dr.
  • Room 2E532 MSC 9760
  • Bethesda, MD 20892-9760

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).

  • Updated: December 5, 2014