Isoflavones Deserve More Attention for Their Effects on Hot Flashes
By Mark Messina, PhD, Executive Director, Soy Nutrition Institute
There is good reason to encourage clinicians to recommend isoflavones for women who experience hot flashes and wish to avoid hormone therapy, despite the limitations of research, as noted below.
Isoflavones may be more potent than selective serotonin reuptake inhibitors (SSRIs) at alleviating menopausal hot flashes. That was the conclusion of a group of Chinese researchers following their extensive evaluation of the clinical research.1 After deducting placebo effects, isoflavones reduced hot flash frequency by 25% compared to slightly less than 14% for SSRIs. In fact, isoflavones were even more beneficial than two drugs used to treat hot flashes, gabapentin and clonidine, which reduced frequency by 14.8% and 18.5%, respectively.
Although SSRIs are generally prescribed for treating depression, the US Food and Drug Administration (FDA) recently approved Brisdelle™ (Noven), which contains 7.5 mg of paroxetine, a SSRI, for the treatment of moderate-to-severe vasomotor symptoms associated with menopause.2
Brisdelle™ was approved by the FDA on the basis of two trials which enrolled 1,184 women3 and found that hot flashes were reduced by an average of 1 to 2 per day in women who had at least 10 hot flashes per day at enrollment.2 In 2012, a meta-analysis by Taku et al.,4 which found isoflavones significantly alleviated hot flashes, involved 1,196 women. Hot flash frequency and severity were reduced by about 21% and about 26% beyond the placebo effect, respectively. The benefits were seen in women regardless of their initial hot flash frequency. Therefore, the sample sizes of isoflavones and paroxetine are similar, and isoflavones reduce symptoms to a similar or greater extent.
But isoflavones have not been widely embraced by clinicians for this purpose and there may be several reasons for this. One is that many of the initial literature reviews, and even some later ones, failed to conclude that isoflavones are efficacious. Unfortunately, these findings were misleading since these reviews didn’t sub-analyze the data according to the genistein content of the isoflavone supplement.
Trials intervening with isoflavone supplements rich in genistein were about twice as potent as supplements low in genistein. Trials have typically intervened with supplements of genistein only, or supplements derived from whole soybeans or derived from the hypcotyledon portion of the bean. In whole-soybean-derived supplements, genistein represents about 50% (similar to soyfoods) of the total isoflavone content whereas in the hypcotyledon-derived supplements genistein represents only about 10%. Thus, it’s to be expected that these studies would yield different results.
In addition, many health professionals and clinicians formed an opinion about the safety of isoflavones on the basis of rodent studies beginning in the late 1990s that showed isoflavones stimulate the growth of existing estrogen-sensitive tumors in ovariectomized athymic mice.5 Fortunately, perspectives are changing with publication of extensive clinical data showing isoflavones don’t adversely affect markers of breast cancer risk6-13 and prospective epidemiologic data showing post-diagnosis soy intake reduces recurrence.14 The recent conclusion of the European Food Safety Authority that isoflavones don’t adversely affect the breast tissue of postmenopausal women should help in this regard.15
Finally, unlike the research of Brisdelle™, which involved two large trials using the same preparation, trials using isoflavones were relatively small and used a variety of soy extracts. Consequently, while collectively the data are impressive, no individual soy extract has been extensively studied. On the other hand, this could actually enhance the case for efficacy because the results come from so many different laboratories and from so many different isoflavone-containing products.