Estrogen augmentation of antidepressants in perimenopausal depression: a pilot study

J Clin Psychiatry. 2005 Jun;66(6):774-80. doi: 10.4088/jcp.v66n0617.


Objective: To investigate the effects of estrogen augmentation on mood and memory in women with perimenopausal depression who had experienced a partial response to antidepressant medications.

Method: In a double-blind, placebo-controlled trial, 17 subjects taking antidepressant medication were randomly assigned to either 0.625 mg/day of conjugated estrogen (N = 11) or matching placebo (N = 6) for 6 weeks. Women between the ages of 40 and 60 years with DSM-IV major depressive disorder (MDD) in partial remission who had been taking antidepressant medication for a minimum of 8 weeks and were experiencing 1 or more perimenopausal symptoms (hot flashes, night sweats, irregular periods, sleep disturbance, memory impairment) were recruited from the community. The primary outcome measures were the final scores for the Hamilton Rating Scale for Depression (HAM-D) and the Buschke Selective Reminding Test. Data were gathered from April 2002 to August 2003.

Results: Women receiving estrogen had a significantly larger decrease in HAM-D scores than women receiving placebo (t = 2.86, df = 15, p = .012). Group differences in tests of verbal memory were not significant, although improved scores in verbal memory were significantly correlated with a decrease in follicle-stimulating hormone (p = .021).

Conclusion: Short-term, low-dose estrogen augmentation of antidepressant medication was significantly associated with improved mood, but not memory, in perimenopausal women with MDD in partial remission.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Estrogens, Conjugated (USP) / pharmacology
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Perimenopause / drug effects
  • Perimenopause / psychology*
  • Pilot Projects
  • Placebos
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Antidepressive Agents
  • Estrogens, Conjugated (USP)
  • Placebos