Equol production in relation to hormones and mammographic breast density among premenopausal women in the United States

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Background: Mammographic breast density and circulating sex hormone concentrations are associated with breast cancer risk. Studies suggest a reduced risk of breast cancer among women who harbor intestinal bacteria that produce equol from the soy isoflavone daidzein (equol-producers; EP) compared with equol non-producers (ENP). In relation to breast cancer risk factors, in one study, postmenopausal EP had lower breast density than ENP; however, no studies have assessed this in premenopausal women. Small studies have compared circulating hormone concentrations among premenopausal EP and ENP, but the findings are unclear.

Objective: To evaluate relationships between equol production and breast density, follicular-phase sex hormone concentrations, and sex hormone binding globulin (SHBG) in a large, well-defined population of premenopausal women in the United States.

Methods: Two hundred women provided a first-void urine sample after 3-days of soy consumption, and 191 provided a fasting blood sample during days 5-9 of their menstrual cycle. Urine samples were analyzed for isoflavones by GC-MS to determine equol-producer phenotype, and serum samples were measured for estrone, estrone-sulfate, estradiol, dehydroepiandrosterone (DHEA), DHEA-sulfate, androstenedione, testosterone, and SHBG by radio-immunoassay and immunometric assays. Percent density on recent (<14 months prior to their clinic visit) mammograms was assessed using a computer-assisted method. T-tests and multiple regression analyses were conducted to assess relationships between equol production and breast density, hormones, and SHBG.

Results: Fifty five (27.5%) women were classed as EP and 145 (72.5%) as ENP. There were no significant differences between EP and ENP in mean breast density (40 vs. 35%, respectively, p>0.05). The difference between EP (n=55) and ENP (n=136) in geometric mean concentration of free testosterone was of borderline statistical significance (4.0 vs. 4.5 pg/ml, respectively, p=0.046); no other differences between EP and ENP in hormones or SHBG were statistically significant (p>0.05). In stepwise multiple regression analyses including age, BMI, and other potential confounders based on a priori hypotheses (p value for entry=0.15), equol-producer status was not significantly associated with breast density, hormone concentrations, or SHBG (p>0.05).

Conclusions: In unadjusted, but not adjusted, analyses, EP had slightly lower concentrations of free testosterone than ENP. No other differences in hormone concentrations, SHBG, or breast density were observed between EP and ENP. This study was conducted in a Western population with low soy consumption patterns; further studies are needed to assess potential interactions between equol-producer status and soy consumption in relation to these breast cancer risk factors. This work was supported by NIH grant R01 CA97366.