Effects of exercise and cardiorespiratory fitness on estrogen metabolism in postmenopausal women

Charles E. Matthews, Joshua N. Sampson, Darren R. Brenner, Steven C. Moore, Kerry S. Courneya, Regina G. Ziegler and Christine M. Friedenreich

DOI: 10.1158/1055-9965.EPI-17-0900



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, estradiol) and 13 estrogen metabolites, including glucuronidated, sulfated, and unconjugated forms, by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 153 postmenopausal women randomized to 12-months of moderate-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-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.


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