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Source: Duncan AM, et al. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab 1999;84:192-197.
Design and Setting: Randomized controlled crossover trial in Minnesota.
Subjects: Fourteen premenopausal women completed the study.
Treatment: High-isoflavone soy powder (2 mg/Kg/d or approximately 128 mg) compared with low-isoflavone (1 mg/Kg/d, or approximately 64 mg) and isoflavone-free (0.15 mg/Kg/d) soy powder.
Dose/Route/Duration: Subjects consumed three soy powders with varying isoflavone content during each of three periods lasting three menstrual cycles plus nine days. Washout period between each period was approximately three weeks. Otherwise, subjects consumed their regular diet with detailed dietary instructions on avoiding phytoestrogens, alcohol, and vitamin supplementation. Plasma estrogen, progesterone, LH, and FSH levels were collected every other day during the last six weeks of each diet cycle.
Outcome Measures: Plasma hormone concentrations, menstrual cycle length, and endometrial effects.
Results: The high-isoflavone diet decreased free T3 and dehydroepi-androsterone sulfate (DHEA-S) during the early follicular phase and decreased estrone levels during the mid-follicular phase. The low-isoflavone diet de-creased LH and FSH during the periovulatory phase. There were no other significant changes in SHBG or hormone levels (including progesterone, testoster-one, prolactin, androstenedione, throxine [T4], TSH, insulin, or cortisol) nor any change in the length of the menstrual cycle, follicular, or luteal phase. Three endometrial biopsies were performed on seven subjects during the study; another five women underwent two biopsies; none showed changes in histological dating.
Funding: NIH grant CA-66016 and general clinical research center grant MO1-RR-00400 from the National Center for Research Resources.
Comments: This is an excellent, well-thought out, carefully conducted trial that looked at multiple hormonal parameters. It is also the first crossover study to compare different isoflavone doses. It is very interesting that only small changes were seen in reproductive hormones (mainly mid-cycle surges of LH and FSH). Although several previous studies found different results on reproductive hormones and menstrual cycle length (see Alternative Therapies in Women’s Health, January 1999, pp. 12-14), this study was longer than previous studies and examined more parameters more carefully. It is the definitive study on this subject so far.
I have only two criticisms. The first is that baseline levels of hormones were either not drawn or not reported. In other words, all diets in this study contained soy, although subjects consumed iso-flavone-free soy during some cycles. The reason that this is important is that it is possible (although admittedly not probable) that other substances in soy besides isoflavones affect hormone levels. The second criticism is that washout periods could have been longer. One uncontrolled high-dose isoflavone (200 mg/d) study in six premenopausal women that did find an effect of soy on hormone levels found that the effect lasted for two to three cycles.1
There has been some concern that soy may have an adverse effect on thyroid function because in vitro studies show an inhibition of thyroid peroxidase. In this study, although free T3 levels were significantly lower in the high (but not the low) isoflavone group, there were no changes in free or total T4, total T3, or TSH levels. Some animal studies have found that soy intake increases T4,2 so it is possible that soy isoflavones inhibit conversion of T4 to T3. Although this has no immediately apparent clinical relevance, it is theoretically possible over time that metabolic rate could decrease. In this study, no changes were seen in body weight, body mass index, or percent body fat. A study of long-term effects of high-isoflavone supplementation on thyroid function tests and metabolic rate would be interesting.
1. Lu LJ, et al. Effects of soya consumption for one month on steroid hormones in premenopausal women: Implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev 1996;5:63-70.
2. Forsythe WA III. Soy protein, thyroid regulation and cholesterol metabolism. J Nutr 1995;125(3suppl):619S-623S.