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Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism.

ABSTRACT: PURPOSE:Physical activity may reduce endogenous estrogens, but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003). METHODS:Postmenopausal women (N = 542) were ages 40 to 72 yr and not currently using hormone therapy. Accelerometers, worn for 7 d, were used to derive measures of average activity (counts per day) and sedentary behavior (<100 counts per minute per day). Estrogen metabolites were measured in 12-h urine samples using liquid chromatography-tandem mass spectrometry. Estrogen metabolites were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent estrogens. Geometric means of estrogen metabolites by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models. RESULTS:High activity was associated with lower levels of estrone and estradiol (P trend = 0.01), whereas increased sedentary time was positively associated with these parent estrogens (P trend = 0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol, and 16-epiestriol (P trend = 0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (P trend ? 0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent estrogens (P trend ? 0.02), whereas increased sedentary time was associated with a lower 16-pathway/parent estrogen ratio (P trend = 0.01). CONCLUSIONS:Higher activity was associated with lower urinary estrogens, possibly through increased estrogen hydroxylation and subsequent metabolism, whereas sedentary behavior may reduce metabolism.

SUBMITTER: Dallal CM

PROVIDER: S-EPMC4861700 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism.

Dallal Cher M CM Brinton Louise A LA Matthews Charles E CE Pfeiffer Ruth M RM Hartman Terryl J TJ Lissowska Jolanta J Falk Roni T RT Garcia-Closas Montserrat M Xu Xia X Veenstra Timothy D TD Gierach Gretchen L GL

Medicine and science in sports and exercise 20160301 3

<h4>Purpose</h4>Physical activity may reduce endogenous estrogens, but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003).<h4>Methods</h4>Postm ...[more]

PMID: 26460631

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Project description:BackgroundEstrogens are recognized causal factors in breast cancer. Interindividual variation in estrogen metabolism may also influence the risk of breast cancer and could provide clues to mechanisms of breast carcinogenesis. Long-standing hypotheses about how estrogen metabolism might influence breast cancer have not been adequately evaluated in epidemiological studies because of the lack of accurate, reproducible, and high-throughput assays for estrogen metabolites.MethodsWe conducted a prospective case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants included 277 women who developed invasive breast cancer (case subjects) and 423 matched control subjects; at PLCO baseline, all subjects were aged 55-74 years, postmenopausal and not using hormone therapy, and provided a blood sample. Liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 15 estrogens and estrogen metabolites, in unconjugated and conjugated forms, including the parent estrogens, estrone and estradiol, and estrogen metabolites in pathways defined by irreversible hydroxylation at the C-2, C-4, or C-16 positions of the steroid ring. We calculated hazard ratios (HRs) approximating risk in highest vs lowest deciles of individual estrogens and estrogen metabolites, estrogens and estrogen metabolites grouped by metabolic pathways, and metabolic pathway ratios using multivariable Cox proportional hazards models. All statistical tests were two-sided.ResultsNearly all estrogens, estrogen metabolites, and metabolic pathway groups were associated with an increased risk of breast cancer; the serum concentration of unconjugated estradiol was strongly associated with the risk of breast cancer (HR = 2.07, 95% confidence interval [CI] = 1.19 to 3.62). No estrogen, estrogen metabolite, or metabolic pathway group remained statistically significantly associated with the risk of breast cancer after adjusting for unconjugated estradiol. The ratio of the 2-hydroxylation pathway to parent estrogens (HR = 0.66, 95% CI = 0.51 to 0.87) and the ratio of 4-hydroxylation pathway catechols to 4-hydroxylation pathway methylated catechols (HR = 1.34, 95% CI = 1.04 to 1.72) were statistically significantly associated with the risk of breast cancer and remained so after adjustment for unconjugated estradiol.ConclusionsMore extensive 2-hydroxylation of parent estrogens is associated with lower risk, and less extensive methylation of potentially genotoxic 4-hydroxylation pathway catechols is associated with higher risk of postmenopausal breast cancer.

Project description:Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4-pathway catechols associated with elevated endometrial cancer risk.

Dataset Information

Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism.

Publications

Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism.

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