Dataset Information

A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.

ABSTRACT:

Background

Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.

Methods

The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided.

Results

Comparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend = .001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ? .0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend = .08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ? .0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend < .0001). Progesterone was not associated with colorectal cancer risk.

Conclusion

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.

SUBMITTER: Murphy N

PROVIDER: S-EPMC5964717 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Publications

A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.

Murphy Neil N Strickler Howard D HD Stanczyk Frank Z FZ Xue Xiaonan X Wassertheil-Smoller Sylvia S Rohan Thomas E TE Ho Gloria Y F GY Anderson Garnet L GL Potter John D JD Gunter Marc J MJ

Journal of the National Cancer Institute 20150801 10

<h4>Background</h4>Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.<h4>Methods</h4>The relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal ...[more]

PMID: 26232761

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Project description:BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.

Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Dataset Information

A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.

Background

Methods

Results

Conclusion

Publications

A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women.

Similar Datasets

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