Menopause Live (21 January, 2013) From IMS

Once again, yet another paper has been published to add to the many studies on phytoestrogens. There are so much data on this issue that one may get lost trying to understand whether there are any real benefits for women who use such products. That’s why I liked this new study, which summarizes its results in a very brief but clear way [1]. Its purpose was to assess the effect of soy isoflavone (80 or 120 mg daily aglycone hypocotyl) on quality of life in postmenopausal women. A multicenter, randomized, double-blind, placebo-controlled, 24-month trial included 403 postmenopausal women (mean age 55 years) using a validated Menopause-Specific Quality of Life questionnaire, containing 29 items grouped into four domains (vasomotor, psychological, physical and sexual). About one-third of women in each arm were equol producers. Domain scores at 1 year and 2 years were similar to those at baseline. There were no differences in domain scores among treatment groups. Thus the conclusion was that soy isoflavone supplementation offers no benefit to quality of life in postmenopausal women.

Comment

My next step was to look for other potential benefits of the same type of soy isoflavone. Another recent study from the same group of investigators looked at metabolic and vascular variables during a 6-week period of daily supplementation with 80 mg soy hypocotyl isoflavones. When compared with placebo and after control for pretreatment values, soy had no effect on arginine flux, citrulline flux, nitric oxide synthesis, blood pressure, forearm blood flow, or estimates of arterial stiffness [2]. Then I remembered that some previous soy studies presented positive bone data. Well, the above research team kindly provided us with relevant information, which actually pointed in the same direction [3]. They reported that, after a 2-year follow-up, daily supplementation with 120 mg soy hypocotyl isoflavones reduced whole-body bone loss but did not slow bone loss at common fracture sites in healthy postmenopausal women. The same team was also keen to look at the safety aspects of such treatment and managed to publish another article covering these data [4]. I was relieved to know that, after 2 years of daily exposure to 80–120 mg soy hypocotyl isoflavones, all clinical chemistry values, except for urea, remained within the normal range. Isoflavone supplementation did not affect blood lymphocyte or serum free thyroxine concentrations. Neither were significant differences in endometrial thickness or fibroids observed. I almost forgot to mention one additional article from the same ‘publishing house’, easing any concern in regard to breast safety [5]. A model with all three mammograms that were performed during the 2-year study period did not show a treatment effect on any mammographic measure, but the change over time was significant; breast density decreased by 1.6%/year across groups (p < 0.001). Stratification by age and body mass index did not reveal any effects in subgroups. These findings offered reassurance that isoflavones do not act like hormone replacement medication on breast density [5]. 

It took me quite some time to grasp the general idea of all these manuscripts which originated from a single, randomized, placebo-controlled, rather large-scale study called OPUS (Osteoporosis Prevention Using Soy). No benefits, no risks related to this particular phytoestrogen. Or, if you will, this type of food supplement has no effect menopause-wise. So why do women use it? Could any of you explain this enigma? The investigators refer to the inconsistency vis-a-vis previous study results and note that their cohort was 5–6 years postmenopause and that women did not have a high baseline level of hot flushes. Also, the specific study product was rich in daidzein, but not in genistein. All these factors may be relevant to the effect on hot flushes and could explain why other products have tested better. Are we still missing hidden benefits to be reported? Anyway, the group of Wong and colleagues managed to exploit their negative results in a most productive way, which actually may be considered as a benefit, may it not?

Amos Pines
Department of Medicine ‘T’, Ichilov Hospital, Tel-Aviv, Israel

References

1. Amato P, Young RL, Steinberg FM, et al. Effect of soy isoflavone supplementation on menopausal quality of life. Menopause 2012 Dec 3. Epub ahead of print.
http://www.ncbi.nlm.nih.gov/pubmed/23211877
2. Wong WW, Taylor AA, Smith EO, Barnes S, Hachey DL. Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women. Am J Clin Nutr 2012;95:1487-94.
http://www.ncbi.nlm.nih.gov/pubmed/22552034
3. Wong WW, Lewis RD, Steinberg FM, et al. Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr 2009;90:1433-9.
http://www.ncbi.nlm.nih.gov/pubmed/19759166
4. Steinberg FM, Murray MJ, Lewis RD, et al. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. Am J Clin Nutr 2011;93:356-67.
http://www.ncbi.nlm.nih.gov/pubmed/21177797
5. Maskarinec G, Verheus M, Steinberg FM, et al. Various doses of soy isoflavones do not modify mammographic density in postmenopausal women. J Nutr 2009;139:981-6.
http://www.ncbi.nlm.nih.gov/pubmed/19321587