Review ArticleOpen Access

Menopausal‭ Transition Raises Vulnerability for Anxiety and Depression Disorders‬‬‬

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DOI: 10.23958/ijirms/vol10-i07/2099· Pages: 272 - 276· Vol. 10, No. 07, (2025)· Published: July 8, 2025
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Abstract

Background & Objective: Hormonal instability during the menopausal transition negatively impacts the limbic and prefrontal circuits, heightening women’s vulnerability to depressive disorders and anxiety. This narrative review integrates basic-science and clinical evidence to clarify how perimenopausal endocrine disturbances increase vulnerability to depression and anxiety, and whether augmenting first-line antidepressants with hormone replacement therapy (HRT) offers superior relief. Methods: English-language literature between the years 1990 – 2024 was searched in PubMed and Google Scholar for studies on menopause, estradiol, depression, anxiety, selective-serotonin/-norepinephrine reuptake inhibitors (SSRI/SNRI), and HRT. Preference was given to randomised controlled trials (RCTs), meta-analyses, and extensive cohort studies; mechanistic papers were included when they provided insight into pathophysiology. Findings were collated qualitatively. Results & Conclusion: Estrogen withdrawal disrupts serotonergic concentration, upregulates HPA-axis reactivity, and alters ERα/ERβ signalling in limbic-cortical circuits, predisposing to mood lability, especially in late perimenopause. Multiple studies and a 2023 network meta-analysis demonstrate that adding systemic estradiol (with or without progesterone) to fluoxetine or similar agents yields higher response and symptomatic remission rates (up to 92% vs. 48%) than either modality alone.

However, systemic HRT also raises breast cancer, thromboembolic, and stroke risk, with the magnitude increasing over prolonged use.

Keywords

Neurobiology links estrogen loss to altered brain signalingSolo Antidepressant therapy often falls shortHRT can increase efficacyBenefits of HRT must be weighed against patient-specific risks and knowledge gapsThe coupling of estrogen and progesterone can mitigate the turbulent fluctuation o

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Author details
Dr‭ Parinda Parikh MD
Department‭ of Psychiatry, Weill Cornell Medical School,‬ White Plains, USA.‬‬
✉ Corresponding Author
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Zoe Gellert
Tulane‭ University, New Orleans, USA‬.
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Dr Arnesh Shukla MD
St‭. Martinus University, Willemstad, Curaçao.‬‬
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Sahia Manepalli
University‭ of South Florida, Tampa, USA.‬‬
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Dr Parthiv‬ Pansuriya‭ MD
Government‭ Medical College Surat, India.‬‬
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Dr Shaurya Kumar Singh MD
Pravara‭ Institute of Medical Sciences, Loni, Maharashtra,‬ India.‬‬
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Dr‬ Himani J Suthar MD
GMERS‭ Medical College and Civil Hospital, Gandhinagar, ‭India.‬‬‬‬‬
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Mahiya Buddhavarapu
University‭ of Pittsburgh, Pennsylvania, USA.‬‬
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Eric Wang
Edgemont‭ Jr. Sr. High School, Westchester, New York,‬ USA.‬‬
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Arushi Kaushik Chandra
NYU‭ Steinhardt School, New York, USA.‬‬
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Dr Mina Oza MD
2nd‭ Arc Associates, White Plains, New York, USA.‬‬‬
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