Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial

Arch Gen Psychiatry. 2001 Jun;58(6):529-34. doi: 10.1001/archpsyc.58.6.529.


Background: Results of previous studies suggest that estrogen improves somatic and mild depressive symptoms experienced by perimenopausal women. This study investigated the efficacy of 17beta-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 17beta-estradiol (100 microgram) 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-Asberg 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 17beta-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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Depression / diagnosis
  • Depression / drug therapy
  • Depression / psychology
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Dysthymic Disorder / diagnosis
  • Dysthymic Disorder / drug therapy
  • Dysthymic Disorder / psychology
  • Estradiol / administration & dosage
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy / methods
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Menopause / psychology*
  • Middle Aged
  • Placebos
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Severity of Illness Index
  • Treatment Outcome


  • Placebos
  • Estradiol
  • Follicle Stimulating Hormone