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 .
One can generalize from the studies review ed 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
BACKGROUND Controversy regarding the antidepressant efficacy of hormone replacement therapy ( HRT ) stems almost from its inception and reflects the same method ological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression .
Since this publication , multiple studies have aim ed 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 .
A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: Effect on mood, cognition and quality of life
The results of several observational studies suggest that the use of estrogen replacement is associated with better mood , cognitive function and quality of life . Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting , enhances cholinergic activity in the brain , decreases brain and plasma levels of beta-amyloid , increases serotonin postsynaptic responsivity and the turnover of noradrenaline , and inhibits monoamine oxidase activity . However , the findings from the Women 's Health Initiative controlled trial showed that hormone replacement ( estrogen plus progestin ) not only failed to improve mood , cognition and quality of life but also increased the risk of dementia . At present , there is limited information about the effect of unopposed estradiol replacement therapy ( ERT ) on the mental health outcomes of women at increased risk of cognitive decline ( aged 70 years and over ) . We design ed the present r and omized , double-blind , placebo-controlled trial to clarify this issue . One hundred and fifteen women were r and omized to treatment with estradiol ( n=58 ; 2 mg per day ) or placebo for a total period of 20 weeks . The outcomes of interest in this study included changes in the Beck Depression Inventory ( BDI ) scores between baseline and week 20 , as well as changes in quality of life scores ( as measured by the SF-36 ) and cognitive function ( CAMCOG , Block Design , Memory for Faces , California Verbal Learning Test ( CVLT ) and verbal fluency ( VF ) ) .  Nineteen women treated with estradiol  and 10 of those treated with  placebo discontinued the use of the medication during trial , most frequently due to adverse reactions ( OR=4.11 , 95 % CI=1.29 - 15.37 ) . Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures ( p>0.05 ) . A separate analysis restricted to women who completed the 20-week-trial produced similar negative results . The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function , mood and quality of life . Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women
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 .
One can generalize from the studies review ed 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
BACKGROUND Controversy regarding the antidepressant efficacy of hormone replacement therapy ( HRT ) stems almost from its inception and reflects the same method ological inconsistencies that have compromised efforts to determine whether the perimenopause is accompanied by an increase in mood symptoms or depression .
Since this publication , multiple studies have aim ed 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 .