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Women’s Health Initiative Clinical Trial Suggests Endogenous Estrogens May Protect Against Colorectal Tumorigenesis in Postmenopausal Women

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Key Points

  • Estrone, free estradiol, and total estradiol levels were inversely associated with the risk of colorectal cancer in postmenopausal women, according to a nested case-control study in the Women’s Health Initiative Clinical Trial.
  • Levels of sex hormone–binding globulin were positively associated with the risk of colorectal cancer.

In a nested case-control study in the Women’s Health Initiative Clinical Trial, reported in Journal of the National Cancer Institute by Murphy et al, endogenous estrogen levels were inversely associated with and sex hormone–binding globulin (SHBG) levels were positively associated with the risk of colorectal cancer in postmenopausal women.

Study Details

The association of circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone, and SHBG with colorectal cancer risk was assessed in 401 postmenopausal case patients and 802 postmenopausal age and race/ethnicity-matched control patients in the Women’s Health Initiative Clinical Trial who were not assigned to receive estrogen-alone or combined estrogen plus progestin treatment.

Associations With Estrogen and SHBG Levels

On multivariate analysis (adjusting for waist circumference, alcohol consumption, family history of colorectal cancer, physical activity, smoking status, and nonsteroidal anti-inflammatory drug use) with additional adjustment for serum insulin, C-reactive protein (CRP), and free insulin-like growth factor 1 (IGF-1), for the 4th vs 1st quartiles, estrone (odds ratio [OR] = 0.44, P trend = .001, ≥ 57.28 vs < 32.50 pg/mL), free estradiol (OR = 0.43, P trend ≤ .0001, ≥ 0.38 vs < 0.18 pg/mL), and total estradiol levels (OR = 0.58, P trend = .08, ≥ 13.90 vs < 7.09 pg/mL) were inversely associated with colorectal cancer risk.

On multivariate analysis, SHBG levels were positively associated with colorectal cancer risk (HR = 2.30, P trend ≤ .0001, for the 4th vs 1st quartiles; ≥ 60.40 vs < 29.70 nmol/L). The positive association was strengthened with additional adjustment for estradiol and estrone and for insulin, CRP, and free IGF-1 (OR = 2.50, P trend < .0001). No association of progesterone with colorectal cancer risk was observed.

The investigators concluded: “Endogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.”

Neil Murphy, PhD, of Imperial College London, is the corresponding author of the Journal of the National Cancer Institute article.

The study was supported by the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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