OBJECTIVE: To examine the efficacy and tolerability of escitalopram (ESCIT) compared to estrogen and progestogen therapy (EPT) for the treatment of symptomatic peri- and postmenopausal women. DESIGN: Forty women (aged 40-60 years) with depressive disorders and menopause-related symptoms were randomly assigned to an 8-week open trial with ESCIT (flexible dose, 10-20 mg/day; fixed dose, 10 mg/day for the first 4 weeks) or estrogen plus progestogen therapy (ethinyl estradiol 5 microg/day plus norethindrone acetate 1 mg/day). Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8. Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessments. RESULTS: Thirty-two women (16 on EPT, 16 on ESCIT) were included in the analyses. Full remission of depression (score of <10 on the Montgomery-Asberg Depression Rating Scale) was observed in 75% (12/16) of subjects treated with ESCIT, compared to 25% (4/16) treated with EPT (P = 0.01, Fisher's exact tests). Remission of menopause-related symptoms (>50% decrease in Greene Climacteric Scale scores) was noted in 56% (9/16) of women treated with ESCIT compared to 31.2% (5/16) on EPT (P = 0.03, Pearson's chi2 tests). Improvement in sleep, hot flashes, and quality of life was observed with both treatments. CONCLUSIONS: ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms. ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy.