Soy intake is associated with increased 2-hydroxylation and decreased 16alpha-hydroxylation of estrogens in Asian-American women

Abstract

Introduction: In Asian and Asian-American women, soy consumption is associated with reduced breast cancer risk, perhaps due to its effects on estrogen production or metabolism. In a sample of Asian-American women, we investigated the associations of usual adult soy intake with the urinary concentrations of 15 estrogens and estrogen metabolites (EM) measured using liquid chromatography-tandem mass spectrometry.

Methods: Participants included 430 Chinese-American, Japanese-American, and Filipino-American women, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California), or Oahu (Hawaii). They were postmenopausal (n = 167) or premenopausal in luteal phase (n = 263) when 12-hour urine samples were collected. Robust linear regression was used to assess soy tertiles as predictors of log-transformed EM measures. Individual and grouped EM were considered as concentrations (pmol/mg creatinine) and as percentages of total EM (%EM).

Results: Factor analysis confirmed that EM groups defined by metabolic pathways appropriately captured covariation in EM profiles. Total EM concentrations were not significantly associated with soy in premenopausal or postmenopausal women. Among all women, %2-hydroxylated EM and %4-hydroxylation pathway EM were 16% higher (P(trend) = 0.02) and 19% higher (P(trend) = 0.03) in the highest versus lowest soy tertiles, respectively. In contrast, 16% hydroxylated EM were 11% lower (P(trend) < 0.01). Results were consistent across ethnic and menopausal groups and after adjustment for westernization measured by birthplace (Asia or United States).

Discussion: Findings suggest that regular soy intake is associated with increased ratios of 2:16-pathway EM and with higher relative levels of 4-hydroxylated EM. The observed variations in estrogen metabolism might modify breast cancer risk.

Figure 1. Covariation among urinary estrogens and estrogen metabolites (EM) in Asian American women by menopausal status

Factor analysis with rotation resulted in extraction of four independent factors with eigenvalues ≥ 1 in premenopausal-luteal and postmenopausal Asian American women. Factors were named according to predominant contributing EM. Each EM is graphed by loadings for the three factors accounting for the most variance in urinary EM concentrations. EM represented by solid shapes are statistically significant contributors to factors that correspond with axes shown in the graph, while EM contributing to the fourth extracted factor for each menopausal group (no axis shown) are represented by open shapes.

Figure 2. Percent difference between highest and lowest tertiles of soy intake in relative levels of urinary estrogens and estrogen metabolites (% of total) by menopausal status, ethnicity, and BMI

Percent difference was calculated based upon regression coefficients associated with the highest tertile of soy intake in robust regression models fitted to predict log-transformed EM measures, using the formula 100 {exp (β̂)−1}. For menopause-specific strata, regression models were adjusted for continuous age and ethnicity (Chinese, Japanese, and Filipino); for ethnic-specific strata, regression models were adjusted for continuous age and menopausal status; for birthplace and BMI, models were adjusted for continuous age, ethnicity, and menopausal status. There was no statistically significant effect modification of the associations between soy and grouped %EM by menopausal status, by ethnicity or by birthplace. * p for interaction < 0.05.