Study population

The first Breast, Estrogens, And Nutrition study (BEAN1) was designed as a 2-year randomized clinical trial to examine the effects of consumption of 2 daily soy servings on sex hormones and mammographic density among premenopausal participants (6, 8). Women were excluded from the study due to pregnancy or breast-feeding, use of estrogen-containing oral contraceptives or dietary supplements containing isoflavones, history of cancer diagnosis, breast implants, or hysterectomy, lack of a regular menstrual period, or intake of >5 soy servings per week. A total of 220 eligible women were randomized to the intervention (high soy diet) or control (low soy diet) group and 189 participants completed 2 years of intervention. The number of dropouts did not differ by group (p=0.53).

The second trial (BEAN2) was a 13-month randomized, crossover study consisting of a 6-month intervention and a 6-month control phase, separated by a 1-month washout period (7). The exclusion criteria were the same as in BEAN1 except for the mammogram requirement. In addition, participants had to be able to produce at least 10 µL of NAF. Of the 96 randomized women, 82 completed the study and provided blood, urine, and NAF samples at baseline and months 6 and 13.

The protocols of the two studies were approved by the University of Hawaii Committee on Human Studies and by the Institutional Review Boards of the participating hospitals. All women signed an informed consent form before entry into the trial and gave written permission to use frozen samples for future analyses. A Data Safety Monitoring Committee reviewed the progress of the studies, reasons for dropouts, and any reported symptoms annually. In both studies, all subjects completed a baseline questionnaire asking for demographic, anthropometric, reproductive, and dietary information.

In the intervention group of BEAN1 or during the high soy diet of BEAN2, women consumed 2 daily servings of various soy foods (tofu, soy milk, roasted soy nuts, soy bars, and soy protein powder) containing approximately 25 mg aglycone equivalents of isoflavones per serving. Dietitians provided dietary counseling on how to replace common dishes with soy foods. In the control group in BEAN1 and during the low soy diet in BEAN2, women were instructed to maintain their regular diet and to consume <3 soy food servings per week. Adherence to the study protocol as assessed by unannounced 24-hour dietary recalls and urinary isoflavone excretion was high in both studies (6, 7).