Depression in menopausal women has been widely described for many years ago and is related to hormonal decrease, mainly estrogens. The use of soy has been proposed as a possible coadjutant alternative to treat menopausal depressive disorder. In the present pilot clinical trial the effect of soybean, antidepressants and the association of soybean with antidepressants was studied in 40 depressive menopausal women for three months. Patients were divided in four groups of 10 women: fluoxetine (10 mg), soybean (100 mg), sertraline (50 mg), and sertraline (50 mg) plus soybean (100 mg). The Hamilton and Zung Depression Scales were used to measure the treatment effects. Values at the beginning and at the end of the study were compared. In all cases a significant difference was observed when the treated groups were compared vs. their untreated situation in both scales (p < 0.001). When a comparison between pre- minus post-treatment Zung scale scores was done, the effect induced by the association of sertraline and soybean was significantly higher than the other groups (p < 0.05). These effects were also seen using the Hamilton scale scores, showing significant differences between the association vs. soybean (p < 0.05) and setraline (p < 0.05) groups, but not vs. fluoxetine group. We conclude that soybean has an antidepressant effect per se, and the association of soybean and antidepressants increases their effects.