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We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich (80.4 mg/day) and isoflavone-poor (4.4 mg/day) soy protein isolate treatment in perimenopausal women.In this double-blind 24-week study, 69 women were randomized to treatment: isoflavone-rich soy protein (n = 24), isoflavone-poor soy protein (n = 24), or whey protein control (n = 21). A Menopausal Index was used to assess change in hot flushes and night sweats, as well as other symptoms, at baseline, week 12, and week 24.Repeated measures analysis of variance indicated no treatment effect on change in hot flush (p = 0.18) and night sweat (p = 0.92) frequency, whereas there was a significant decline in hot flush (p = 0.0003) and night sweat (p = 0.0007) frequency with time in all treatment groups. χ2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point, as well as no treatment effect on frequency or severity of other vasomotor symptoms. At the completion of the study, we found no treatment effect on retrospective perception of frequency, duration, or severity of hot flushes or night sweats. Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms, this indicated either a placebo effect or simply an improvement in symptoms during the study.In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.