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Birth After 30 Lowers Endometrial Cancer Risk

November 1, 2012
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By Rebecca Bowers. Consulting Editor, Contraceptive Technology Update. Ms. Bowers reports no financial relationships relevant to this field of study.

This article originally appeared in the November 2012 issue of Contraceptive Technology Update.

Women who last give birth at age 40 or older have a 44% decreased risk of endometrial cancer when compared to women who have their last birth under the age of 25, according to results of a new international study.1 Study findings indicate the risk begins to decrease after age 30 by about 13 percentage points for each five-year delay in last births.

Cancer of the endometrium is the most common gynecologic malignancy in the U.S. and accounts for 6% of all cancers in women.2 In 2012, the American Cancer Society estimates there will be 47,130 new cases of uterus cancer (endometrial cancer and uterine sarcomas), with 8010 deaths attributed to the two cancers.2 Symptoms can include abnormal vaginal bleeding, spotting or other discharge (particularly after menopause), pelvic pain or mass, and weight loss (usually seen in later stages of the disease.)3 Risk of disease increases with age. More than half of all endometrial cancers are diagnosed in women ages 50-69.3

What are possible causes for endometrial cancer? Exposure of the endometrium to estrogen that is "unopposed" by progesterone is a common cause. Since pregnancy results in large changes in exogenous estrogen and progesterone levels, data indicates that pregnancy influences the incidence of endometrial cancer.1

What prompted the international research team to look at the impact of later childbirth on the incidence of endometrial cancer? Researchers analyzed impact of age at last birth, because data indicates parity and number of children are important factors influencing woman's risk of developing endometrial cancer, says V. Wendy Setiawan, PhD, lead investigator and assistant professor in the Department of Preventive Medicine at the University of Southern California Keck School of Medicine in Los Angeles.

However, whether timing of birth and age of giving birth are also associated with risk is unclear, says Setiawan. This question led the researchers to look at age at birth in relation to endometrial cancer risk. The current analysis focused on age at last birth because previous studies indicate that women who gave birth to their last child after 30 or 35 have lower risk of endometrial cancer compared to women who had their last birth at a younger age.4-5

To perform the analysis, the research team pooled individual-level data from four cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium, a National Cancer Institute-supported consortium dedicated to studying the etiology of endometrial cancer through collaboration. A total of 8671 cases of endometrial cancer and 16,562 controls were included in the analysis.

After adjusting for known risk factors, data indicate that endometrial cancer risk declined with increasing age at last birth (P [trend] < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval [CI], 0.85-0.90). Women who last gave birth at age 40 or older had a 44% decreased risk compared with women who had their last birth under age 25 (95% CI, 47-66).

The protective association was similar across the different age-at-diagnosis groups and for the two major tumor histologic subtypes (type I and type II), the researchers report. No effect modification was observed by body mass index, parity, or exogenous hormone use, they state.1

The current study, which is the largest to date to examine the issue, confirms the finding that late age at last birth is independently associated with a reduced risk of endometrial cancer, says Setiawan. Data also demonstrate that the protective association persisted for decades, she notes.

Talk with Patients

Researchers point to several potential biologic mechanisms that might explain why age at last birth might protect against endometrial cancer. They include:

  • women who are capable of becoming pregnant at an older age might possess a "healthy" endometrium or experience fewer anovulatory cycles;
  • prolonged exposure to progesterone during pregnancy might be more protective at older ages, when endometrial cancer development normally occurs;
  • shedding of premalignant and malignant cells from the mucosal lining of the uterine cavity, which are more likely to exist with advancing age, might occur during childbirth.1

Woman who choose to space their births might obtain additional protection against endometrial cancer with the use of combined oral contraceptives (COCs). According to Contraceptive Technology, women who use COCs for at least a decade reduce their risk of developing endometrial cancer by 80% compared to nonusers.6,7 This protection against cancer endures for up to 20 years following pill discontinuation.8

For women who have endometrial hyperplasia, a precursor to endometrial carcinoma, Contraceptive Technology authors advise use of COCs as a treatment to reverse the condition.7

References

1. Setiawan VW, et al. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Am J Epidemiol 2012;176:269-278.

2. American Cancer Society. Cancer Facts and Figures 2012. Atlanta: American Cancer Society, 2012.

3. American Cancer Society. Endometrial Cancer. Fact sheet. Accessed at http://bit.ly/OnHjUg.

4. Pfeiffer RM, et al. Timing of births and endometrial cancer risk in Swedish women. Cancer Causes Control 2009;20:1441-1449.

5. Bevier M, et al. Does the time interval between first and last birth influence the risk of endometrial and ovarian cancer? Eur J Cancer 2011;47:586-591.

6. 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 1987;257:796-800.

7. Nelson AL, Cwiak C. Combined oral contraceptives (COCs). In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.

8. Schlesselman JJ. Risk of endometrial cancer in relation to use of combined oral contraceptives. A practitioner's guide to meta-analysis. Hum Reprod 1997;12:1851-1863.