Schmidt PJ, Wei SM, Martinez PE, et al. - In this study, the short-term efficacies of three estrogen-like compounds under placebo-controlled conditions were investigated in women with perimenopause-related depression (PMD). Researchers randomized women with PMD in a double-blind parallel design to one of four treatments: transdermal 17-beta estradiol (TE) (100 mcg/d); oral raloxifene (60 mg/d); a proprietary phytoestrogen compound, Rimostil (1,000 mg twice/d); or placebo for 8 weeks. Sixty-six women were assigned randomly into the trial, four women dropped out, and 62 were evaluated in the final data analysis. They carried out cognitive tests at pretreatment baseline and at the end of the trial. In PMD, there were no significant therapeutic benefits of TE, Rimostil, or raloxifene vs placebo. However, they found improvements in depression ratings between TE vs Rimostil. Therefore, the data do not support the role of ERbeta compounds in the treatment of PMD (and may infer a more important role of ERalpha).