ReviewThe American journal of psychiatry2015
Ovarian hormone fluctuation, neurosteroids, and HPA axis dysregulation in perimenopausal depression: a novel heuristic model.
Review in The American journal of psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
125 citing papers in PubMed, 4 syntheses or guidelines pooled it, 260 citations in OpenAlex.
- Pharmacotherapy, acupoint stimulation, and psychotherapy for perimenopausal women with anxiety, depression, and panic disorder: a systematic review and network meta-analysis of randomized controlled trials.Frontiers in psychiatry · 2026Pooled it
- The effect of Tibolone treatment on depression, anxiety and mood in women: a meta-analysis and systematic review of randomized controlled trials.Archives of women's mental health · 2025Pooled it
- Effects ofFrontiers in reproductive health · 2025Pooled it
- Depression in Turner Syndrome: A Systematic Review.Archives of sexual behavior · 2020Pooled it
- Characterizing the spectrum of distress symptoms in midlife women with perimenopausal depression.Journal of affective disorders · 2026Trial
- Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial.Psychoneuroendocrinology · 2023Trial
- Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women - A randomized clinical trial.Psychoneuroendocrinology · 2022Trial
- The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression.Menopause (New York, N.Y.) · 2021Trial
- Effects of perimenopausal transdermal estradiol on self-reported sleep, independent of its effect on vasomotor symptom bother and depressive symptoms.Menopause (New York, N.Y.) · 2019Trial
- Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial.JAMA psychiatry · 2018Trial
- Estradiol variability, stressful life events, and the emergence of depressive symptomatology during the menopausal transition.Menopause (New York, N.Y.) · 2016Trial
- Using the National Curriculum in Reproductive Psychiatry to Enhance and Standardize Fellowship Training.Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry · 2026Article
- Exploring the Physiological Effects and Mechanisms of Gamma-Aminobutyric Acid in Food Systems.Foods (Basel, Switzerland) · 2026Review
- Embodied pathways of recovery: interoceptive change and the reduction of depressive symptoms following Tai Chi in women aged 40-55 years.Archives of women's mental health · 2026Article
- Synaptic Actions of Estradiol in the Brain's Reward System: Linking Mechanisms to Behavior and Disease.Biological psychiatry global open science · 2026Review
- Nutritional Interventions for Perimenopausal Anxiety and Depression Targeting Tryptophan and GABA Pathways: A Narrative Review.Nutrients · 2026Review
- Advances in Perinatal Depression: A Focus on Screening and Treatment.Journal of clinical medicine · 2026Review
- Understanding Depression in Women Across the Lifespan: Hormonal Insights From Brain Imaging.Brain and behavior · 2026Review
- HPA/HPG axes dysfunction: assessing the interrelations between diminished ovarian reserve and mental health.Journal of ovarian research · 2026Review
- Observational
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveIn this conceptual review, the authors propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition ("perimenopausal depression") involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation.
methodThe relevant literature in perimenopausal depression, including prevalence, predictors, and treatment with estrogen therapy, was reviewed. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development.
resultsThe rate of major depressive disorder and clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and derived neurosteroids result in alterations in regulation of the HPA axis by γ-aminobutyric acid (GABA). The authors' heuristic model suggests that for some women, failure of the GABAA receptor to regulate overall GABA-ergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress and generating greater vulnerability to depression.
conclusionsThe proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of midlife to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders, such as postpartum depression and premenstrual dysphoric disorder.
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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.