Endometrial Cancer Prevention (PDQ®)–Health Professional Version

  • Resize font
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Who Is at Risk?

Endometrial cancer occurs in postmenopausal women with an average age at diagnosis of 60 years. Estrogen, both endogenous and exogenous, is associated with endometrial proliferation, hyperplasia, and cancer. Thus, risk factors include endometrial hyperplasia, reproductive factors (nulliparity, early menarche and late menopause), polycystic ovarian syndrome, postmenopausal estrogen therapy, obesity with adult weight gain, and tamoxifen use. Women with hereditary nonpolyposis colorectal cancer syndrome have an increased risk of endometrial cancer, as do women with a first-degree relative with endometrial cancer.

Overview

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

Factors with Adequate Evidence for an Increased Risk of Endometrial Cancer

Endometrial hyperplasia

Based on solid evidence, endometrial hyperplasia is associated with concurrent [1] or subsequent development of cancer, an association first recognized in 1932.[2]

Magnitude of Effect: Women with hyperplasia and atypia have a 50% risk of concurrent cancer.[1]

  • Study Design: Observational case series.
  • Internal Validity: Good.
  • Consistency: Good.
  • External Validity: Good.

Hormone therapy (HT) with estrogen: Unopposed estrogen

Based on solid evidence, unopposed estrogen is associated with an increased risk of endometrial cancer. This excess risk can be eliminated by adding continuous progestin to estrogen therapy, but this combination is associated with an increased risk of breast cancer.[3-6] (Refer to the PDQ summary on Breast Cancer Prevention for more information.)

Magnitude of Effect: The associated risk of endometrial cancer in women using unopposed estrogen for 5 or more years is more than twofold higher than in women who do not use the hormone.

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

Based on solid evidence, in addition to the risk of endometrial cancer, unopposed estrogen is associated with an increased risk of endometrial hyperplasia, stroke, and thrombosis.[4,6]

Magnitude of Effect: Unopposed estrogen after a mean follow-up of 6.8 years: Approximately a 39% relative increase in stroke and a 34% relative increase in pulmonary embolus.

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

Selective estrogen receptor modifiers (SERMs)

Based on solid evidence, more than 2 years of tamoxifen use is associated with an increased risk of endometrial cancer.[7] A similar SERM, raloxifene, does not have this association. [8,9]

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 and diabetes

Based on solid evidence, being overweight or obese, adult weight gain, and diabetes are associated with an increased risk of endometrial cancer. [10,11]

Magnitude of Effect: The risk of endometrial cancer increases 1.59-fold per 5 kg/m2 change in body mass.[11]

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

Factors With Adequate Evidence for a Decreased Risk of Endometrial Cancer

Increasing parity and lactation

Based on solid evidence, increased parity and duration of lactation are associated with a decreased risk of endometrial cancer.[12]

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.[13,14]

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

Oral contraceptives

Benefits

Based on solid evidence, at least 1-year 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.[15]

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

Magnitude of Effect: Use of oral contraceptives for 5 years was associated with an RR reduction of 24% (risk ratio, 0.76; 95% CI, 0.73–0.78) and persisted for more than 30 years. Ten years of use was associated with an absolute reduction in risk before age 75 years from 2.3 per 100 women to 1.3 per 100 women.

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.[16,17]

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.

Smoking

Benefits

Based on solid evidence, cigarette smoking is associated with a decreased risk of endometrial cancer.[18]

Magnitude of Effect: Smokers have a reduced risk of endometrial cancer of approximately 20% among prospective studies (RR, 0.81; 95% CI, 0.74–0.88) and case-control studies (odds ratio, 0.72; 95% CI, 0.66–0.79).[18]

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

Based on solid evidence, cigarette smoking is associated with cardiovascular disease and cancers of the head and neck, lung, bladder, and pancreas. Cigarette smokers have a decreased life expectancy—they live at least 10 years fewer than nonsmokers.[19]

Intervention With Inadequate Evidence of an Association With Endometrial Cancer

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 three age periods was not associated with a decrease in endometrial cancer incidence.[20]

Magnitude of Effects: RR of endometrial cancer for women who intentionally lost at least 20 pounds 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. Widra EA, Dunton CJ, McHugh M, et al.: Endometrial hyperplasia and the risk of carcinoma. Int J Gynecol Cancer 5 (3): 233-235, 1995. [PUBMED Abstract]
  2. Taylor HC: Endometrial hyperplasia and carcinoma of the body of the uterus. Am J Obstet Gynecol 23 (3): 309-32, 1932.
  3. Beral V, Bull D, Reeves G, et al.: Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 365 (9470): 1543-51, 2005 Apr 30-May 6. [PUBMED Abstract]
  4. 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]
  5. Furness S, Roberts H, Marjoribanks J, et al.: Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev (2): CD000402, 2009. [PUBMED Abstract]
  6. Grady D, Gebretsadik T, Kerlikowske K, et al.: Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol 85 (2): 304-13, 1995. [PUBMED Abstract]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. Aune D, Navarro Rosenblatt DA, Chan DS, et al.: Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol 26 (8): 1635-48, 2015. [PUBMED Abstract]
  12. 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]
  13. 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]
  14. 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]
  15. Collaborative Group on Epidemiological Studies on Endometrial Cancer: Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 16 (9): 1061-70, 2015. [PUBMED Abstract]
  16. 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]
  17. 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]
  18. Zhou B, Yang L, Sun Q, et al.: Cigarette smoking and the risk of endometrial cancer: a meta-analysis. Am J Med 121 (6): 501-508.e3, 2008. [PUBMED Abstract]
  19. Centers for Disease Control and Prevention: Smoking and Tobacco Use. Atlanta, Ga: Centers for Disease Control and Prevention, Office on Smoking and Health, 2015. Available Online. Last accessed June 30, 2016.
  20. 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 60,050 new cases expected to occur in 2016.[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 10,470 women will die of endometrial cancer in 2016. Incidence rates of endometrial cancer have increased by 1.3% per year since 1988 among women younger than 50 years and increased by 1.9% per year since 2005 among women 50 years and older. From 2003 to 2012, death rates from endometrial cancer increased by 1.1% per year.[1]

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).[3] Higher mortality from endometrial cancer in African Americans is at least partly attributable to lower socioeconomic issues that impair access to care.[4]

Endometrial cancer risk is associated with endogenous and exogenous factors associated with estrogen effects. [5-7] Thus, risk factors for endometrial cancer include reproductive factors such as nulliparity, early menarche, and late menopause, obesity, polycystic ovarian syndrome, postmenopausal estrogen use and tamoxifen use.

Women with hereditary nonpolyposis colorectal cancer syndrome have a lifetime risk of endometrial cancer of up to 60%.[8] (Refer to the PDQ summary on Genetics of Breast and Gynecologic Cancers for additional information on inherited risk.)

Factors With Adequate Evidence for an Increased Risk of Endometrial Cancer

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 ovarian syndrome, may also be related to increased estrogen exposure.[7]

Postmenopausal estrogen therapy

An association between postmenopausal estrogen replacement therapy and endometrial cancer was reported in 1975 [9] and confirmed soon after.[10,11] 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),[12-15] and a persistent effect lasting more than 10 years after 1 year of use.[16] When these findings were publicized, prescriptions for estrogen declined sharply, followed rapidly by a drop in endometrial cancer incidence.[17]

Combination estrogen-progestin replacement therapy

Postmenopausal estrogen was long recognized to be associated with the risk of endometrial hyperplasia, often a precursor of endometrial cancer.[18] In addition, progestational agents were known to be effective in the treatment of uterine neoplasms.[19-21] Consequently, combined estrogen-progesterone postmenopausal hormone therapy (HT) was proposed to avoid the endometrial cancer risk associated with unopposed estrogen.[22,23] Unfortunately, the combined therapy increases the risk of breast cancer, so it is not recommended to treat menopausal symptoms.

Selective estrogen receptor modulators (SERMs): 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.[24] Since then, confirmation of the association has been provided by randomized clinical trials using tamoxifen for breast cancer treatment and prevention [25-28] 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 cases per 1,000 women for those receiving tamoxifen versus 0.91 cases per 1,000 women 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.[29]

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).[30] 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 (odds ratio [OR], 3.0; 95% CI, 1.3–6.9).[31]

Obesity, weight gain, metabolic syndrome, and diabetes

Elevated body mass index (BMI), obesity, and weight gain 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.[32] Alternatively, obesity has been associated with a reduction in levels of sex hormone-binding globulin (SHBG), which may protect against endometrial cancer by decreasing bioavailable estrogen.[33] Obesity has been associated with several factors known to increase the risk of endometrial cancer, including upper-body or central adiposity, polycystic ovarian syndrome, and physical inactivity.[34,35]

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.[36]

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.[37-39] 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.[40-43] An increased risk is observed across all measures of adiposity, such as BMI, waist circumference, waist-to-hip ratio, and weight gain.[44]

A meta-analysis of prospective studies observed an RR of 1.39 (95% CI, 1.29–1.49) among nonusers and 1.09 (95% CI, 1.02–1.16) among HT users for each 5 kg increase in adult weight gain.[45] Another meta-analysis also observed a stronger association between BMI and the risk of endometrial cancer in never-users of HT than in ever-users of HT.[46]

A meta-analysis examining the association between metabolic syndrome and endometrial cancer observed an increased risk associated with metabolic syndrome (RR, 1.89; 95% CI, 1.34–2.67) and with each component of the syndrome (BMI and/or waist circumference, blood pressure, and triglyceride levels), except low high-density lipoprotein cholesterol.[47] In an umbrella analysis of studies of the association between type 1 diabetes and cancer, endometrial cancer was one of only a few sites with robust evidence of an association.[48]

Genetic predisposition

Women with inherited conditions such as Lynch syndrome, Cowden syndrome, and polycystic ovarian 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.) However, in addition to inherited syndromes with highly penetrant genes, having a family history of endometrial cancer in a first-degree relative also is associated with an increased risk of cancer.[49] A meta-analysis, including case-control and cohort studies, observed an increased risk of 1.82 (95% CI, 1.65–1.98) associated with a history of endometrial cancer in a first-degree relative, with an estimated cumulative absolute risk of about 3% (95% CI, 2.8–3.4).[49]

This familial risk may result from inherited genetic predisposition and other common factors that exist is families, such as shared culture or learned behaviors.

Factors With Adequate Evidence for a Decreased Risk of Endometrial Cancer

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.[50] 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).[51] 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.[52]

Oral contraceptives

Oral contraceptive usage confers a long-term reduction in the risk of endometrial cancer. A meta-analysis combining data from 36 epidemiological studies including 27,276 women observed a risk reduction of 0.76 (95% CI, 0.73–0.78) for every 5 years of use. The lower risk persisted for more than 30 years after the last use of oral contraceptives.[53] Ten years of oral contraceptive use was associated with an absolute risk reduction of endometrial cancer before age 75 from 2.3 to 1.3 per 100 women, among women from highly developed countries.[53]

Physical activity

A meta-analysis combined data from prospective studies of recreational activity (nine studies) and occupational activity (five studies) to determine whether activity is association with endometrial cancer.[54] The highest versus the lowest category of recreational activity was associated with an RR for endometrial cancer of 0.73 (95% CI, 0.58–0.93); the RR of endometrial cancer for the highest versus lowest category of occupational physical activity, based on job classification, was 0.75 (95% CI, 0.68–0.83.) Further investigation using the metabolic equivalent of task (MET) and combining data from case-control and cohort studies, revealed a decrease in endometrial cancer risk with activities in the range up to 50 MET hours per week (up to 15 hours/week).[45]

Smoking

Ever-smokers of at least 20 cigarettes per day have a decreased risk of endometrial cancer, with greater risk reduction in postmenopausal women and in current smokers. This effect has been seen in prospective cohort and case-control studies and was summarized in a meta-analysis.[55] The many well-documented harms of smoking are most evident in the increased risk of cardiovascular diseases and other cancers, to the extent that smokers have at least a 10-year decrease in life expectancy, compared with nonsmokers.[56]

Interventions With Inadequate Evidence of an Association With Endometrial Cancer

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,[57] 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 pounds (RR, 0.93; 95% CI, 0.60–1.44). The obvious limitation of this study is the reliance on retrospective self-reported data.[57]

Fruits, vegetables, and vitamins

Studies of the association between endometrial cancer and diet, phytoestrogens, soy, and vitamin D have been negative.[58-62] Multivitamin use has little or no influence on the risk of common cancers, including endometrial cancer, or on total mortality in postmenopausal women.[63]

References
  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  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 June 30, 2016.
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. Brown SB, Hankinson SE: Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Steroids 99 (Pt A): 8-10, 2015. [PUBMED Abstract]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. Gray LA Sr, Christopherson WM, Hoover RN: Estrogens and endometrial carcinoma. Obstet Gynecol 49 (4): 385-9, 1977. [PUBMED Abstract]
  14. 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]
  15. 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]
  16. 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]
  17. Austin DF, Roe KM: The decreasing incidence of endometrial cancer: public health implications. Am J Public Health 72 (1): 65-8, 1982. [PUBMED Abstract]
  18. Gusberg SB: Precursors of corpus carcinoma estrogens and adenomatous hyperplasia. Am J Obstet Gynecol 54(6): 905-927, 1947.
  19. Gusberg SB: Hormone-dependence of endometrial cancer. Obstet Gynecol 30 (2): 287-93, 1967. [PUBMED Abstract]
  20. 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]
  21. KISTNER RW: Histological effects of progestins on hyperplasia and carcinoma in situ of the endometrium. Cancer 12: 1106-22, 1959 Nov-Dec. [PUBMED Abstract]
  22. Whitehead MI: The effects of oestrogens and progestogens on the postmenopausal endometrium. Maturitas 1 (2): 87-98, 1978. [PUBMED Abstract]
  23. 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]
  24. Killackey MA, Hakes TB, Pierce VK: Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treat Rep 69 (2): 237-8, 1985. [PUBMED Abstract]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. 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]
  33. 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]
  34. Troisi R, Potischman N, Hoover RN, et al.: Insulin and endometrial cancer. Am J Epidemiol 146 (6): 476-82, 1997. [PUBMED Abstract]
  35. Barry JA, Azizia MM, Hardiman PJ: Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 20 (5): 748-58, 2014 Sep-Oct. [PUBMED Abstract]
  36. 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]
  37. 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]
  38. 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]
  39. Schapira DV, Kumar NB, Lyman GH, et al.: Upper-body fat distribution and endometrial cancer risk. JAMA 266 (13): 1808-11, 1991. [PUBMED Abstract]
  40. 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]
  41. 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]
  42. 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]
  43. 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]
  44. Aune D, Navarro Rosenblatt DA, Chan DS, et al.: Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol 26 (8): 1635-48, 2015. [PUBMED Abstract]
  45. Keum N, Ju W, Lee DH, et al.: Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer 135 (3): 682-94, 2014. [PUBMED Abstract]
  46. Crosbie EJ, Zwahlen M, Kitchener HC, et al.: Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 19 (12): 3119-30, 2010. [PUBMED Abstract]
  47. Esposito K, Chiodini P, Capuano A, et al.: Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine 45 (1): 28-36, 2014. [PUBMED Abstract]
  48. Tsilidis KK, Kasimis JC, Lopez DS, et al.: Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ 350: g7607, 2015. [PUBMED Abstract]
  49. Win AK, Reece JC, Ryan S: Family history and risk of endometrial cancer: a systematic review and meta-analysis. Obstet Gynecol 125 (1): 89-98, 2015. [PUBMED Abstract]
  50. 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]
  51. 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]
  52. 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]
  53. Collaborative Group on Epidemiological Studies on Endometrial Cancer: Endometrial cancer and oral contraceptives: an individual participant meta-analysis of 27 276 women with endometrial cancer from 36 epidemiological studies. Lancet Oncol 16 (9): 1061-70, 2015. [PUBMED Abstract]
  54. Moore SC, Gierach GL, Schatzkin A, et al.: Physical activity, sedentary behaviours, and the prevention of endometrial cancer. Br J Cancer 103 (7): 933-8, 2010. [PUBMED Abstract]
  55. Zhou B, Yang L, Sun Q, et al.: Cigarette smoking and the risk of endometrial cancer: a meta-analysis. Am J Med 121 (6): 501-508.e3, 2008. [PUBMED Abstract]
  56. Centers for Disease Control and Prevention: Smoking and Tobacco Use. Atlanta, Ga: Centers for Disease Control and Prevention, Office on Smoking and Health, 2015. Available Online. Last accessed June 30, 2016.
  57. 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]
  58. 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.
  59. 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.
  60. 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]
  61. 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]
  62. 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]
  63. 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 (06/30/2016)

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.

This summary was comprehensively reviewed and extensively revised.

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.

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 NCI website's Email Us. 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:

PDQ® Screening and Prevention Editorial Board. PDQ Endometrial Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/uterine/hp/endometrial-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389477]

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 Managing Cancer Care page.

Contact Us

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

  • Updated: June 30, 2016

Most text on the National Cancer Institute website may be reproduced or reused freely. The National Cancer Institute should be credited as the source. Please note that blog posts that are written by individuals from outside the government may be owned by the writer, and graphics may be owned by their creator. In such cases, it is necessary to contact the writer, artist, or publisher to obtain permission for reuse.

We welcome your comments on this post. All comments must follow our comment policy.