SynthesisDepression and anxiety2015
EFFICACY OF ESTRADIOL IN PERIMENOPAUSAL DEPRESSION: SO MUCH PROMISE AND SO FEW ANSWERS.
Synthesis in Depression and anxiety, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- Pooled it
- Menopause and suicide: A systematic review.Women's health (London, England)Pooled it
- The efficacy and safety of Femoston combined with Baoqing granules for kidney Yin deficiency in perimenopausal women: a randomized, double-blind, placebo-controlled trial.Frontiers in endocrinology · 2026Trial
- Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial.Psychoneuroendocrinology · 2023Trial
- The Role and Mechanism of Estrogen in Perimenopausal Depression.Current neuropharmacology · 2026Review
- The 2025 Menopausal Hormone Therapy Guidelines - Korean Society of Menopause.Journal of menopausal medicine · 2025Review
- Considering the role of estradiol in the psychoneuroimmunology of perimenopausal depression.Brain, behavior, & immunity - health · 2024Article
- Melatonin Ameliorates Depressive-Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Role of Estrogen across Multiple Disease Mechanisms.Current issues in molecular biology · 2024Review
- The intersection between menopause and depression: overview of research using animal models.Frontiers in psychiatry · 2024Review
- Article
- [Cognitive and psychoemotional changes in menopausal transition: The possibility of medical correction].Problemy endokrinologii · 2023Article
- Neuroendocrine pathogenesis of perimenopausal depression.Frontiers in psychiatry · 2023Review
- Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women.JAMA network open · 2022Article
- Disinhibition of right inferior frontal gyrus underlies alpha asymmetry in women with low testosterone.Biological psychology · 2021Article
- Pulsed administration for physiological estrogen replacement in mice.F1000Research · 2021Article
- Hormonal Treatments for Major Depressive Disorder: State of the Art.The American journal of psychiatry · 2020Review
- The 2020 Menopausal Hormone Therapy Guidelines.Journal of menopausal medicine · 2020Review
- Is Postpartum Depression Different From Depression Occurring Outside of the Perinatal Period? A Review of the Evidence.Focus (American Psychiatric Publishing) · 2020Review
- PI3K-AKT Signaling Activation and Icariin: The Potential Effects on the Perimenopausal Depression-Like Rat Model.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundControversy 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.
methodsThe purpose of this systematic review is to examine the findings and quality of the evidence amassed since Zweifel and O'Brien's meta-analysis.
resultsOf the 24 studies meeting criteria for review, only five RCTs examined depressed subjects, and only two of the study samples were solely perimenopausal.
conclusionsOne 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.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.