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A Double-blind, Randomized, Placebo-Controlled Trial

Cláudio de Novaes Soares, MD, PhD; Osvaldo P. Almeida, MD, PhD; Hadine Joffe, MD; Lee S. Cohen, MD

Arch Gen Psychiatry. 2001;58:529-534.

Background  Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17ß-estradiol for the treatment of clinically significant depressive disorders in endocrinologically confirmed perimenopausal women.

Methods  Perimenopausal women (aged 40-55 years, with irregular menstrual periods and serum concentrations of follicle-stimulating hormone >25 IU/L), meeting criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder, according to DSM-IV, were randomized to receive transdermal patches of 17ß-estradiol (100 µg) or placebo in a 12-week, double-blind, placebo-controlled study. A 4-week washout period followed the 12-week treatment phase. Outcome measures were the Montgomery-Åsberg Depression Rating Scale and Blatt-Kupperman Menopausal Index scores.

Results  Fifty women were enrolled in the study; 26 met DSM-IV criteria for major depressive disorder, 11 for dysthymic disorder, and 13 for minor depressive disorder. Remission of depression was observed in 17 (68%) women treated with 17ß-estradiol compared with 5 (20%) in the placebo group (P = .001). Subjects responded similarly to estradiol treatment, regardless of DSM-IV diagnosis. Patients treated with estradiol sustained antidepressant benefit of treatment after the 4-week washout period, although somatic complaints increased in frequency and intensity. Treatment was well tolerated and adverse events were rare in both groups.

Conclusion  Transdermal estradiol replacement is an effective treatment of depression for perimenopausal women.

From the Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil (Dr Soares); the Department of Psychiatry and Behavioral Science, University of Western Australia, Perth (Dr Almeida); and Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Harvard Medical School, Boston (Drs Soares, Joffe, and Cohen).

Corresponding author: Cláudio de Novaes Soares, MD, PhD, Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Harvard Medical School, 15 Parkman St, WACC 812, Boston, MA 02114 (e-mail: csoares{at}partners.org).

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