Weiser M, Levi L, Zamora D, et al. – In this study that included a cohort of 200 women with schizophrenia who were equally randomized to receive either a 200-μg estradiol patch or placebo added to antipsychotics, researchers independently replicated the outcomes of the impact of estradiol on schizophrenia in women of childbearing age. At baseline, the mean positive PANSS score was 19.6 for both groups combined. At week 8, the mean positive PANSS score was 14.4 in the placebo group and 13.4 in the estradiol group. Individuals who received add-on estradiol patches had statistically significant improvements in the primary outcome measure, PANSS positive subscale points, compared with those who received placebo. This impact occurred in nearly all 100 individuals older than 38 years of age. Younger participants received no benefit from estradiol. In the estradiol group (n = 15) vs the placebo group (n = 1), breast tenderness was more prevalent, as was weight gain. Overall, these study findings independently replicated the finding that transdermal estradiol may be an effective add-on treatment for women of childbearing age with schizophrenia and extend it, demonstrating improvements in negative symptoms and demonstrating that the effect could be specific to those older than 38 years of age. The investigators noted, however, that the study results should be viewed within the context of the differences in the natural course of schizophrenia between females and males.