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Endometrial Cancer Prevention (PDQ®)

  • Last Modified: 02/28/2014

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Overview

Intervention Associated With Decreased Risk
        Oral contraceptives
        Physical activity
Factors Associated With Decreased Risk
        Increasing parity and lactation
Factors Associated With Increased Risk
        Hormone therapy (HT)
        Selective estrogen receptor modifiers
        Obesity
Interventions of Unproven or Disproven Effect
        Weight loss

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]