The Effect of Soy Consumption on the Urinary 2:16-Hydroxyestrone Ratio in Postmenopausal Women Depends on Equol Production Status but Is Not Influenced by Probiotic Consumption

Abstract

Some epidemiologic studies reported an association between a low ratio of urinary 2-hydroxyestrogens (2-hydroxyestradiol + 2-hydroxyestrone) to 16alpha-hydroxyestrone (2:16OHE(1)) and increased breast cancer risk. Some studies show that soy consumption increases this ratio, and it is suggested that this effect may reduce breast cancer risk. We hypothesized that consumption of probiotic bacteria would alter fecal bacteria and enzymes involved in soy isoflavone metabolism, thereby increasing isoflavone bioavailability and enhancing the beneficial effects of soy on estrogen metabolism. Breast cancer survivors (n = 20) and controls (n = 20) were given 4 treatments for 6 wk each, separated by 2-wk washout periods, in a randomized, crossover design: soy protein (26.6 +/- 4.5 g protein/d containing 44.4 +/- 7.5 mg isoflavones/d); soy protein + probiotics (10(9) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (26.6 +/- 4.5 g protein/d); and milk protein + probiotics. Survivors tended to have a lower baseline urine 2:16OHE(1) ratio than controls (P = 0.10). In the group as a whole, soy consumption tended to increase urinary 2-hydroxyestrogens (P = 0.07) and 16alpha-hydroxyestrone (P = 0.11) but had no effect on the urinary 2:16OHE(1) ratio. When subjects were divided into groups by plasma concentrations and urinary levels of the daidzein metabolite equol, soy increased urinary 2-hydroxyestrogens (P = 0.01) and the 2:16OHE(1) ratio (P = 0.04) only in subjects with high plasma equol concentrations. None of these results were influenced by probiotic consumption. These results are consistent with studies that found lower urine 2:16OHE(1) ratios in women with breast cancer and suggest that soy consumption increases this ratio only in women who are equol producers.

Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women

“…The effect of EPA and DHA on estrogen metabolism might be different and needs further investigation. The 6-week duration of intervention was short in this study; however, the metabolic pathway of estrogens was found to be altered in 7 days by indole-3-carbinol (Michnovicz et al, 1997), 12 days by broccoli diet (Kall et al, 1996), 4 weeks or 6 weeks by soy (Lu et al, 2000a;Nettleton et al, 2005). Therefore, 6-week intervention in this study might be adequate.…”

Equol Status Modifies the Association of Soy Intake and Mammographic Density in a Sample of Postmenopausal Women

“…The first, a small controlled intervention trial (n = 34 postmenopausal women) by Nettleton et al (41), showed that soy protein supplementation resulted in increased urinary 2-hydroxy estrogens and an increased ratio of excreted 2:16 hydroxy-estrogens in the subgroup of participants who excreted high levels of equol. Whereas prospective studies have not consistently supported an association of circulating levels of these particular estrogen metabolites or their ratio with breast cancer risk (42)(43)(44), a growing body of research supports a role in breast carcinogenesis for the quinones of catechol estrogens, which are unstable and therefore difficult to measure directly in an epidemiologic setting (45)(46)(47).…”

Does equol production determine soy endocrine effects?

“…The other hypothesis for breast cancer protection by isoflavones and equol is that both may alter oestrogen metabolism away from the genotoxic oestrogen metabolites (increased risk) toward the protective metabolites (that decrease the risk of breast cancer) [101][102][103][104][105]. Xu et al showed that a diet rich with isoflavones reduced the synthesis of genotoxic metabolites 16a-OH E1 and 4-hydroxyestrogens, increased the synthesis of the protective metabolite 2-OH E1, and lowered the ratio of 2-OH E1 to 16a-OH E1 (also known to be protective for breast cancer) in both pre-and postmenopausal women [101,102].…”