title: EFFICACY OF ESTRADIOL IN PERIMENOPAUSAL DEPRESSION: SO MUCH PROMISE AND SO FEW ANSWERS.
abstract: BACKGROUND
  Controversy regarding the antidepressant efficacy of hormone replacement therapy (HRT) stems almost from its inception and reflects the same methodological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression. Methodologic differences of note (other than study design) include menopausal state (perimenopause vs. postmenopause), determination of state (earlier studies used age as a proxy measure), baseline symptomatology (asymptomatic vs. depressive symptoms vs. syndromic depression), route of hormone administration (transdermal vs. oral), and symptom or syndrome measure. Zweifel and O'Brien's 1997 meta-analysis included 26 studies of the effects of menopausal HRT on depressed mood and revealed an overall effect size of 0.68. This moderate to large effect size, showing lower ratings of depressed mood in treated patients compared with controls, implicated HRT as a potential treatment of or prophylactic for depression in menopausal women. Since this publication, multiple studies have aimed to discern the relationship between HRT and menopausal mood.
  
  
  METHODS
  The purpose of this systematic review is to examine the findings and quality of the evidence amassed since Zweifel and O'Brien's meta-analysis.
  
  
  RESULTS
  Of the 24 studies meeting criteria for review, only five RCTs examined depressed subjects, and only two of the study samples were solely perimenopausal.
  
  
  CONCLUSIONS
  One can generalize from the studies reviewed here only with great caution, but there is little evidence to support the use of estradiol to improve mood in nondepressed patients (not surprisingly) and some evidence to support the antidepressant efficacy of estradiol in perimenopausal but not postmenopausal women.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: David R
authors.initials: DR
authors.lastname: Rubinow
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Sarah Lanier
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: Behavioral Endocrinology Branch, NIMH, Department of Health and Human Services, Bethesda, Maryland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmidt
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Susan
authors.initials: S
authors.lastname: Girdler
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Bradley
authors.initials: B
authors.lastname: Gaynes
mesh_terms: D003863:Depression / Q000188:drug therapy*; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D047648:Perimenopause / Q000187:drug effects / Q000502:physiology*
chemical_list: D004967:Estrogens; D004958:Estradiol
keywords: HRT; depression; hormone; menopause; mood disorder