The Effect of Daily Soy Isoflavone Supplementation for One Year on Endogenous Steroid Metabolism in Healthy Postmenopausal Women

Abstract

Isoflavones are soy phytoestrogens that have been shown to exert hormonal effects and suggested to be anticarcinogenic. Few studies have investigated long‐term soy isoflavone supplementation on endogenous estrogen metabolism in postmenopausal women. A random subset of samples was selected from the original randomized, double‐blinded, placebo‐controlled 2‐year trial of daily supplementation with 80 or 120 mg hypocotyl isoflavones in healthy postmenopausal women (OPUS trial). Thirty‐eight women (age 41–61y, 95% Caucasian, 0 mg/d placebo group: n=12; 80 mg/d group: n=13, 120 mg/d group: n=12). Each isoflavone tablet had an average content of 34.10 mg aglycone equivalent of total isoflavones (daizein: 22.01 mg, glycitein, 13.54 mg; genistein: 5.00 mg). Serum and urine samples from baseline and after 1year, were analyzed for serum isoflavone metabolites by high performance liquid chromatography (HPLC) – mass spectrometry (MS) and urine steroid metabolites by an ultra performance liquid chromatography (UPLC)‐tandem mass spectrometry (MS/MS) method. Serum concentrations of daidzein, dihydrodaidzein, and O‐desmethylangolensin (O‐DMA) were significantly increased from baseline after 1 year supplementation of both 80 mg and 120 mg isoflavones (p<0.04 for all). The increase of O‐DMA also had a significant dose‐response effect in the 120 mg/d group compared to 80 mg/d group (p<0.05), which validated the study compliance. 28% participants in the supplementation groups were equol producers. Urine concentrations of estrone (E1) and estradiol (E2) were significantly increased (p=0.05 and p=0.02) by 120mg isoflavone supplementation compared to baseline. The change of E2 in the 120mg group was significantly correlated with the change of serum dihydrodaidzein (r=0.69, p=0.01). The concentrations of other endogenous steroids, including estrogen metabolites and the ratio of 2‐OH E1/16α‐OH E1 were not changed in both 80 mg/d and 120 mg/d groups. In conclusion, 1‐year daily supplementation of 120 mg isoflavones increased urine E1 and E2 concentrations, but did not affect the appearance of potential carcinogenic or anticarcinogenic estrogen metabolites. Our findings suggest daily soy hypocotyl isoflavone supplementation for one year has minimal effect on endogenous steroid metabolism in healthy postmenopausal women.Support or Funding InformationFunding from UC Davis Department of Nutrition unrestricted research funds (Steinberg)