Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women

Abstract

Background: Soy isoflavones are naturally occurring phytochemicals with weak estrogenic cellular effects. Despite numerous clinical trials of short-term isoflavone supplementation, there is a paucity of data regarding longer-term outcomes and safety.

Objective: Our aim was to evaluate the clinical outcomes of soy hypocotyl isoflavone supplementation in healthy menopausal women as a secondary outcome of a trial on bone health.

Design: A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg aglycone equivalent soy hypocotyl isoflavones plus calcium and vitamin D on the health of 403 postmenopausal women. At baseline and after 1 and 2 y, clinical blood chemistry values were measured and a well-woman examination was conducted, which included a mammogram and a Papanicolaou test. A cohort also underwent transvaginal ultrasound measurements to assess endometrial thickness and fibroids.

Results: The baseline characteristics of the groups were similar. After 2 y of daily isoflavone exposure, all clinical chemistry values remained within the normal range. The only variable that changed significantly was blood urea nitrogen, which increased significantly after 2 y (P = 0.048) but not after 1 y (P = 0.343) in the supplementation groups. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. No significant differences in endometrial thickness or fibroids were observed between the groups. Two serious adverse events were detected (one case of breast cancer and one case of estrogen receptor-negative endometrial cancer), which was less than the expected population rate for these cancers.

Conclusion: Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

FIGURE 1.

Flow chart of the study design and subject participation throughout the study. GI, gastrointestinal; HRT, hormone replacement therapy. Reproduced with permission from reference .

FIGURE 2.

Mean (±SD) fasting blood concentrations of daidzein in participants at baseline and after 1 and 2 y of treatment. Blood concentrations of daidzein were compared between the 3 treatment groups over time by generalized estimating equation (GEE) techniques to assess the effect of group, time, and group × time interaction with repeated measures accounted for. A significant group × time interaction (P < 0.001) was detected; therefore, groups were compared at each time point by using contrasts and multiple comparison procedures provided by GEE analysis. The data were log transformed before analysis because of a highly skewed distribution. The blood concentrations of daidzein after 1 and 2 y of isoflavone treatment (80 or 120 mg/d) were significantly (P < 0.001) greater than their respective baseline values. The blood concentrations of daidzein in subjects receiving the 120-mg/d treatment were also significantly greater (P < 0.001) than the respective values in subjects who received the 80-mg/d treatment.