Table 1.

Summary of included placebo-controlled trials of soy isoflavones

Source	Number of participants	Sample	Therapy	Study duration	Study design	Baseline of hot flashes/results
Albertazzi et al. [7]	104	Post-menopausal women; ≥7 hot flashes per day; average age, 52–53 years; Italy.	Isolated soy protein, 76 mg of isoflavones (aglycone units)	12 weeks	Parallel	The baseline frequency: 11.4(10.7–12.7) per day for the soy group, 10.9(10.2–11.8) per day for the placebo group; Reduced frequency (45% vs. 30%, P < 0.01) with soy vs. placebo.
Quella et al. [8]	177	Women had breast cancer; ≥14 hot flashes per week; over 18 years of age; United States	Soy tablet, 150 mg daily (with 40–45% genistein, 40–45% daidzein, and 10–20% glycitein)	4 weeks	Crossover	The baseline frequency: 7 ± 4.5 per day; No differences in frequency or severity score between groups, 36% of placebo vs. 24% of soy tablet.
Scambia et al. [9]	39	Post-menopausal women; average age, 53–54 years; Italy	Soy tablet, 50 mg daily of genistein and daidzein	6 weeks	Parallel	The baseline frequency: 33 ± 5.1 per week for the soy group, 27 ± 5.1 per week for the placebo group; Reduced frequency (40% vs. 25%, P < 0.05) with soy tablet vs. placebo.
Upmalis et al. [10]	177	Healthy post-menopausal women; ≥5 hot flashes per day; aged 50 years or older; American	Soy tablet, 50 mg daily of genistein and daidzein	12 weeks	Parallel	The baseline frequency: 8.8 ± 6.2 per day for the soy group, 9.4 ± 6.0 per day for the placebo group; No difference in frequency between groups.
Knight et al. [11]	24	Post-menopausal women; ≥3 hot flashes per day; aged 40–45 years; Australia.	Soy powder, 134.4 mg daily of genistein, daidzein and glycitein compounds.	12 weeks	Parallel	The baseline frequency: 50.2 ± 13.6 per week for the soy group, 56.2 ± 26.5 per week for the placebo group; Reduced frequency (43% vs. 20%, P = 0.32) with soy vs. placebo
Faure et al. [12]	75	Post-menopausal women; ≥7 hot flashes per day; average age, 53–54 years; France	Soy capsule, 70 mg daily of genistein and daidzein	16 weeks	Parallel	The baseline frequency: 10.1 ± 6.4 per day for the soy group, 9.4 ± 3.4 per day for the placebo group; Reduced frequency with soy vs. placebo (61%vs. 21%, P = 0.01).
Van Patten et al. [13]	157	Women had breast cancer; ≥10 hot flashes per week; average age, 55–56 years; England.	Soy beverage, 90 mg of isoflavones	12 weeks	Parallel	The baseline frequency: 7.1 ± 4.3 per day for the soy group, 7.4 ± 6.4 per day for the placebo group; No differences in frequency between groups. Reduced frequency (25.4% vs. 33.8%) with soy vs. placebo.
Penotti et al. [14]	62	Post-menopausal women; ≥7 hot flashes per day; aged 45–60 years; Italy	Soy tablet, 72 mg daily isoflavone	6 mo	Parallel	The baseline frequency: 9.5 ± 3.4 per day for the soy group, 8.8 ± 1.4 per day for the placebo group; 40% reduction in frequency in both groups; No between-group differences.
Crisafulli et al. [15]	90	Post-menopausal women; aged 47–57 years; Italy.	Genistein, 54 mg daily;	1y	Parallel	The baseline frequency: 4.6 ± 3.2 per day for the genistein group, 4.7 ± 3.2 per day for the placebo group; Reduced frequency for genistein vs. placebo (24% mean difference, P < 0.01).
Campagnoli et al. [16]	36	Healthy post-menopausal women; ≥5 hot flashes per day; aged 45–58 years; Italy	200 mg standardized soy extract, (with15% daidzein, 15% genistein, 20% saponin)	12 weeks	Crossover	The baseline frequency: 38 per week; No differences in frequency between groups. Reduced frequency (26.5% vs. 24.3%) with Soy vs. placebo.
Levis et al. [17]	99	Post-menopausal women; aged 45–60 years; Canada	Muffins with 42 mg of isoflavones	16 weeks	Parallel	The baseline frequency: 4.1 ± 2.4 per day for the isoflavones group, 4.7 ± 3.0 per day for the placebo group; Reduced frequency (17.4% vs. 19.7%) with soy vs. placebo.
Nahas et al. [18]	80	Healthy post-menopausal women; ≥5 hot flashes per day; aged 45 years or older; Brazil	Soy capsule, 100 mg daily of isoflavone	10 mo	Parallel	The baseline frequency: 9.6 ± 3.9 per day for the soy group, 10.1 ± 4.9 per day for the placebo group; Reduced frequency (3.1 ± 2.3 and 5.9 ± 4.3 per day, P < 0.001) with soy tablet vs. placebo.
D'Anna et al. [19]	236	Post-menopausal women; average age, 54–55 years; Italy	Genistein tablet, 54 mg daily of total isoflavone	24 mo	Parallel	The baseline frequency: 4.4 ± 3.4 per day for the genistein group, 4.2 ± 3.7 per day for the placebo group; In the genistein group, there was a significant decrease in the mean number (−56.4%) of the hot flushes.
Ferrari [20]	180	Post-menopausal women or 6 weeks after bilateral oophorectomy; ≥5 hot flashes per day; aged 40–65 years; Italy	Soybean extract, 80 mg daily isoflavones (with 60 mg genistein and genistin, 16 mg daidzein and daizin, 3 mg glycitein and glycitin).	12 weeks	Parallel	The baseline frequency: 8.0 ± 3.3 per day for the isoflavones group, 7.5 ± 2.8 per day for the placebo group; Reduced frequency (41.2% vs. 29.3%, P = 0.023) with soy vs. placebo at 12 weeks.
Evans et al. [21]	84	Healthy post-menopausal women; ≥40 hot flashes per week; aged 40–65 years; Canada	Capsules, 30 mg genistein	12 weeks	Parallel	The baseline frequency: 9.4 ± 3.8 per day for the genistein group, 9.9 ± 3.9 per day for the placebo group; Reduced frequency (51.2% vs. 29.8%, P = 0.046) with genistein vs. placebo at 12 weeks.
Ye et al. [22]	90	Post-menopausal women; aged 45–60 years; China	Soy germ isoflavone extract powder, low dose group, 84 mg daily isoflavones; high dose group, 126 mg daily isoflavones (with 52% daidzin, 15% genistin, and 33% glycitin aglcone equivalents)	24 weeks	Parallel	The baseline frequency: 20 ± 11.0 per week for the genistein group, 21 ± 12.5 per week for the placebo group; Reduced frequency (44.3% vs. 48.5% vs. 27.8, P < 0.01) with isoflavone low dose group vs. isoflavone high dose group vs. placebo.