Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study.

OBJECTIVE: To evaluate the effect of soy isoflavones and melatonin in relieving menopausal symptoms. METHODS: Double-blind, multicenter, randomized trial performed according to a 2 x 2 factorial design. Treatment groups: (1) soy isoflavones+melatonin; (2) soy isoflavones alone; (3) melatonin alone; (4) placebo. 80 mg of soy isoflavones, 3 mg of pure melatonin or placebo were supplemented to participants for 3 months. Severity of menopausal symptoms was recorded at baseline and after 3 months using the Greene Climacteric Scale. RESULTS: 388 consecutive women were screened: not eligible 98, refused informed consent 28. Randomized 262 and analyzed 232; twelve women withdrew because of adverse events. Median percent differences between basal and final scores were 39% in the isoflavones + melatonin group, 38% in the isoflavones alone group, 26% in the melatonin alone group and 38% in the placebo group. Placebo response was much higher than planned, making it meaningless to perform any statistical test. With regard to somatic and vasomotor symptoms, outcome was similar among the four groups, whereas improvement of psychological symptoms was higher in the isoflavones+melatonin group than in the other three. CONCLUSIONS: Present data do not show any advantage of isoflavones or melatonin over placebo for the relief of menopausal symptoms. However, the effect in psychological symptoms in the isoflavones + melatonin group should be further investigated.