Twenty-five RCTs (n=2,348) were included, of which five were crossover RCTs.
All but 3 RCTs reported double-blinding. Seven RCTs described adequate allocation concealment. Eleven RCTs reported the use of intention-to-treat analysis, but only one clearly included all randomised patients in the analysis of the results. The mean drop-out rate was 15.5%. Only 6 studies assessed the outcomes using a validated symptom score.
Soy foods, beverages and powders (11 RCTs, n=1,094).
The total daily dose in 8 RCTs ranged from 34 to 134 mg. Of 8 RCTs evaluating hot flushes, seven showed no statistically significant difference between soy products and placebo and one favoured soy products. None of the 8 RCTs assessing symptom scores found a difference between treatments in overall symptom scores.
Soy extract (9 RCTs, n=854).
The studies used different products with daily isoflavone doses ranging from 50 to 150 mg. Of 5 RCTs (including the two largest RCTs with 177 patients each) assessing hot flushes, three found no significant difference between treatments and two favoured soy extract over placebo. Of 5 RCTs assessing symptom scores, one found soy extract significantly improved total symptom scores (assessed using the Kupperman Index) compared with placebo, while another found no significant difference between treatments in total Kupperman Index score or a visual analogue scale. The other RCTs reported effects for specific items in scales or only reported changes from baseline.
Red clover extracts (5 RCTs, n=400).
All studies used the same proprietary formula, Promensil. One study also included a treatment arm with Rimostil. Only the two smallest RCTs (30 patients each) found significant improvements in hot flush frequency with red clover. There was no statistically significant difference between red clover extract and placebo in pooled hot flush frequency (WMD -0.60, 95% CI: -1.71, +0.51). Statistically significant heterogeneity was found (P=0.04).The results were similar after including a higher dose treatment arm, grouping studies by drug dose and analysing only studies with adequate allocation concealment. None of the 4 RCTs using the Greene Climateric Scale to assess symptoms found any difference between treatments.
Women treated for breast cancer (3 RCTs, n=396).
There was no significant difference between phytoestrogens and control in terms of either hot flushes (2 RCTs) or symptom scores (1 RCT).
Adverse effects (12 RCTs). Two of the 12 RCTs reported increased adverse effects with phytoestrogens compared with control; one found increased gastrointestinal effects (47% versus 22% with placebo), while the other found increased rates of gastrointestinal effects or supplement unpalatability (75% versus 17% with control; plus 25% dropped out due to dislike of taste of soy). The other studies reported similar rates of adverse effects between treatments.