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Endometrial Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Overview


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.


Based on solid evidence, being overweight or obese is associated with an increased risk of endometrial cancer.[20,21,22]

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.


  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.
  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.
  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.
  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.
  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.
  6. Newcomb PA, Trentham-Dietz A: Breast feeding practices in relation to endometrial cancer risk, USA. Cancer Causes Control 11 (7): 663-7, 2000.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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