Background: Prolonged sitting and physical inactivity are associated with higher circulating levels of estrogens. It is unknown whether these risk factors are associated with circulating androgens/ androgen metabolites, another set of hormones implicated in the etiology of cancers in postmenopausal women. Methods: We conducted a cross-sectional analysis of 1,782 postmenopausal women in the Women's Health Initiative Observational Study. Serum concentrations of 12 androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting time were selfreported at baseline. We performed linear regression to estimate geometric means (GM) of androgen/androgen metabolite concentrations (pmol/L) according to physical activity and sitting time, adjusting for potential confounders and stratified by menopausal hormone therapy (MHT) use. Results: Physical activity (≥15 vs. 0 MET-h/wk) was inversely associated with estrogen-to-androgen ratios among never/former MHT users (adj-GM = 37.5 vs. 49.6 unconjugated estrone:androstenedione; 20.2 vs. 30.3 unconjugated estradiol:testosterone; all Ptrend ≤ 0.03) but was not associated among current MHT users. Prolonged sitting (≥10 vs. ≤5 h/d) was positively associated with these ratios among both never/former (adj-GM = 44.2 vs. 38.3, Ptrend=0.10; adj-GM=23.4 vs. 20.2, Ptrend=0.17; respectively) and current MHT users (adj-GM = 197 vs. 147; 105 vs. 75.5; respectively; all Ptrend ≤0.02), but the associations were statistically significant among current MHT users only. The associations persisted after adjustment for BMI. After adjustment for adrenal androgens, physical activity and sitting were not associated with androgen metabolites. Conclusions: Physical activity and sitting were associated with serum estrogen-to-androgen ratios but not androgen metabolites.
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