Urinary estrogen metabolites in two soy trials with premenopausal women

BACKGROUND: Soy consumption may protect against breast cancer through modification of estrogen metabolism. OBJECTIVES: We examined the effect of soy foods on urinary estrogens and the 2-hydroxy (OH)/16 alpha-OH estrone (E-1) ratio in two dietary interventions with premenopausal women. SUBJECTS/METHODS: The Breast, Estrogens, And Nutrition (BEAN1) study was a 2-year randomized trial and BEAN2 a 13-month randomized crossover study. In both interventions, study participants consumed a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/week. Urine samples were collected at baseline and at the end of the diet periods, analyzed for nine estrogen metabolites by liquid chromatography mass spectrometry, and adjusted for creatinine levels. For BEAN1, two samples for 188 participants and for BEAN2, three samples for 79 women were analyzed. We applied mixed-effects regression models with log-transformed values of estrogen metabolites and soy intake as the exposure variable. RESULTS: In BEAN1, no effect of the high-soy diet on individual estrogen metabolites or hydroxylation pathways was observed. The median 2-OH/16 alpha-OHE1 ratio decreased non-significantly in the intervention group from 6.2 to 5.2 as compared with 6.8 and 7.2 in the control group (P = 0.63). In BEAN2, only 4-OHE1 was significantly lower after the high-soy diet. Interaction terms of the high-soy diet with equol producer status, ethnicity and weight status revealed no significant effect modification. CONCLUSIONS: Contrary to our hypothesis and some previous reports, the results from two well-controlled dietary interventions do not support an effect of a high-soy diet on a panel of urinary estrogen metabolites and the 2-OH/16 alpha-OHE1 ratio.