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Mood disorders in midlife women: understanding the critical window and its clinical implications

Soares, Claudio N. MD, PhD, FRCPC, MBA(c)

doi: 10.1097/GME.0000000000000193
Clinical Corner: Invited Review

Objective Menopausal transition and early postmenopausal years have been described as a “window of vulnerability” for the development of depressive symptoms or depression (new or recurrent) in some women. This article aims to review contributing factors to the emergence of menopause-related depression, some of the key challenges to its proper identification and management, and evidence on effective treatment strategies.

Methods A body of evidence (animal data, epidemiologic studies, and clinical studies) was reviewed to disentangle some of the complex interactions between changes in sex hormones and reproductive function, physical health, and mood in midlife women. Special focus was given to the window of vulnerability framework.

Results Despite evidence of a critical window for new onset of depression, a prior depressive episode (particularly if related to reproductive events) remains the strongest predictor of mood symptoms or depression during midlife years. Vasomotor symptoms, anxiety, and other health-related issues also modulate the risk for depression. Mechanistically, estrogen plays an important role in mood and cognitive regulation. Transdermal estradiol, as well as serotonergic and noradrenergic antidepressants, have shown efficacy in the management of depression in this population. Other evidence-based treatment options (hormonal, pharmacologic, and behavioral) are available to clinicians and health professionals.

Conclusions A more comprehensive diagnostic approach should be used in symptomatic midlife women. Ultimately, researchers hope to develop preventive strategies and treatments that could be tailored to multiple symptom domains and improve overall functioning.

From the Women’s Health Concerns Clinic, St Joseph’s Healthcare, Hamilton, Ontario, Canada.

Funding/support: None.

Financial disclosure/conflicts of interest: In the past 3 years, C.N.S. has received research and educational grants from the National Alliance for Research on Schizophrenia and Depression (Brain and Behavior Foundation), AstraZeneca, Bristol Myers Squibb, Pfizer Inc, Eli Lilly, and Canadian Institutes for Health Research. He has served as a consultant to Pfizer Inc, AstraZeneca, Noven Pharmaceuticals, Lundbeck, and Bristol Myers Squibb. He has also served as a board member at Lundbeck, Noven Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, and Pfizer Inc.

Address correspondence to: Claudio N. Soares, MD, PhD, FRCPC, MBA(c), Women’s Health Concerns Clinic, 301 James Street South FB638, Hamilton, ON, Canada L8P 3B6. E-mail:;

Received September 19, 2013; revised and accepted November 25, 2013.

© 2014 by The North American Menopause Society.