The authors used a randomized, double-blind, placebo-controlled clinical trial study design to investigate the efficacy and safety of short-term estrogen therapy in decreasing aggressive behaviors in elderly patients with moderate-to-severe dementia. Estrogen therapy was associated with lower total aggression scores (P<0.030) and with decreased frequency of physical aggression (P<0.019) over the 4-week trial. Verbally aggressive behaviors were decreased relative to control subjects, although this effect was not statistically significant. No drug-vs.-placebo differences were found for resistive, sexual, or self-directed aggressive behaviors. No adverse effects from the estrogen were observed during the course of the study.