Dataset Information

Effects of Exercise and Cardiorespiratory Fitness on Estrogen Metabolism in Postmenopausal Women.

ABSTRACT:

Background

Lowering endogenous estrogen levels is one mechanism whereby physical activity may lower postmenopausal breast cancer risk. Several prospective studies have suggested that increased 2-hydroxylation of estrogens may also reduce postmenopausal breast cancer risk, but whether or not exercise alters estrogen metabolism through this mechanism is unclear.

Methods

We measured total circulating concentrations of parent estrogens (estrone and estradiol) and 13 estrogen metabolites, including glucuronidated, sulfated, and unconjugated forms, by stable isotope dilution LC/MS-MS in 153 postmenopausal women randomized to 12 months of moderate-to-vigorous exercise and 153 controls. We also explored associations with cardiorespiratory fitness measured by treadmill.

Results

Although women randomized to exercise averaged 178 minutes/week of exercise over 12 months, their cardiorespiratory fitness was 13% greater than controls at 12 months (P = 0.0001), and total estradiol was reduced by 10% (P = 0.04); there were no statistically significant effects of exercise on circulating concentrations of estrogen metabolites in the 2-, 4-, or 16-pathways, or on the 2-pathway/parent estrogens ratio. However, we observed a statistically significant association between increased fitness and reduced concentration of 2-pathway metabolites (P < 0.05).

Conclusions

We found no evidence that 12 months of moderate-to-vigorous exercise or increased fitness changed estrogen metabolism in a way that might reduce breast cancer risk.

Impact

The protective effect of exercise on postmenopausal breast cancer is unlikely to be mediated by changes in estrogen metabolism.

SUBMITTER: Matthews CE

PROVIDER: S-EPMC7899052 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Effects of Exercise and Cardiorespiratory Fitness on Estrogen Metabolism in Postmenopausal Women.

Matthews Charles E CE Sampson Joshua N JN Brenner Darren R DR Moore Steven C SC Courneya Kerry S KS Ziegler Regina G RG Friedenreich Christine M CM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20180814 12

<h4>Background</h4>Lowering endogenous estrogen levels is one mechanism whereby physical activity may lower postmenopausal breast cancer risk. Several prospective studies have suggested that increased 2-hydroxylation of estrogens may also reduce postmenopausal breast cancer risk, but whether or not exercise alters estrogen metabolism through this mechanism is unclear.<h4>Methods</h4>We measured total circulating concentrations of parent estrogens (estrone and estradiol) and 13 estrogen metabolit ...[more]

PMID: 30108098

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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:Aerobic exercise has been associated with reduced burden of brain and cognitive changes related to Alzheimer's disease (AD). However, it is unknown whether exercise training in asymptomatic individuals harboring risk for AD improves outcomes associated with AD. We investigated the effect of 26 weeks of supervised aerobic treadmill exercise training on brain glucose metabolism and cognition among 23 late-middle-aged adults from a cohort enriched with familial and genetic risk of AD. They were randomized to Usual Physical Activity (PA) or Enhanced PA conditions. Usual PA received instruction about maintaining an active lifestyle. Enhanced PA completed a progressive exercise training program consisting of 3 sessions of treadmill walking per week for 26 weeks. By week seven, participants exercised at 70- 80% heart rate reserve for 50 minutes per session to achieve 150 minutes of moderate intensity activity per week in accordance with public health guidelines. Before and after the intervention, participants completed a graded treadmill test to assess VO2peak as a measure of cardiorespiratory fitness (CRF), wore an accelerometer to measure free-living PA, underwent 18F-fluorodeoxyglucose positron emission tomography imaging to assess brain glucose metabolism, and a neuropsychological battery to assess episodic memory and executive function. VO2peak increased, sedentary behavior decreased, and moderate-to-vigorous PA increased significantly in the Enhanced PA group as compared to Usual PA. Glucose metabolism in the posterior cingulate cortex (PCC) did not change significantly in Enhanced PA relative to Usual PA. However, change in PCC glucose metabolism correlated positively with change in VO2peak. Executive function, but not episodic memory, was significantly improved after Enhanced PA relative to Usual PA. Improvement in executive function correlated with increased VO2peak. Favorable CRF adaptation after 26 weeks of aerobic exercise training was associated with improvements in PCC glucose metabolism and executive function, important markers of AD.

Dataset Information

Effects of Exercise and Cardiorespiratory Fitness on Estrogen Metabolism in Postmenopausal Women.

Background

Methods

Results

Conclusions

Impact

Publications

Effects of Exercise and Cardiorespiratory Fitness on Estrogen Metabolism in Postmenopausal Women.

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