Reproductive hormone sensitivity and risk for depression across the female life cycle: A continuum of vulnerability?

Reproductive hormone sensitivity and risk for depression across the female life cycle: A continuum of vulnerability?


J Psychiatry Neurosci 2008;33(4):331-43

Claudio N. Soares, MD, PhD; Brook Zitek, DO

Soares — Women’s Health Concerns Clinic, Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ont.; Zitek — Global Medical Affairs, Wyeth Research, Collegeville, Pa.


Throughout most of their lives, women are at greater risk for depression than men. Hormones and neurotransmitters share common pathways and receptor sites in areas of the brain linked to mood, particularly through the hypothalamic-pituitary-gonadal axis. It has been hypothesized that women presenting with episodes of depression associated with reproductive events (i.e., premenstrual, postpartum, menopausal transition) may be particularly prone to experiencing depression, in part because of a heightened sensitivity to intense hormonal fluctuations. The menopausal transition, for example, appears to represent a window during which some women might be more vulnerable to the development of first onset or recurrent depressive symptoms and major depressive episodes. In this review, we examine the association between hormone changes and increased risk of developing depression. Some of the underlying mechanisms that may contribute to such an increased risk are discussed critically, with a special emphasis on the events occurring during the menopausal transition. Last, we explore some of the clinical and therapeutic implications of hormone-modulated depression in women.


Durant la majeure partie de leur vie, les femmes sont plus vulnérables à la dépression que les hommes. Les hormones et les neurotransmetteurs ont des voies et des récepteurs communs dans des régions du cerveau reliées à l’humeur, en particulier l’axe hypothalamus-hypophyse-gonades. On a posé en hypothèse que les femmes qui vivent des épisodes de dépression associés à des événements génésiques (c.-à-d. prémenstruels, postnataux, transition vers la ménopause) peuvent être particulièrement vulnérables à la dépression, en partie parce qu’elles sont plus sensibles aux fluctuations hormonales intenses. La transition vers la ménopause, p. ex., semble représenter une période pendant laquelle des femmes peuvent être plus vulnérables à l’apparition de symptômes dépressifs nouveaux ou répétitifs et à des épisodes dépressifs majeurs. Dans cette synthèse, nous analysons le lien entre les changements hormonaux et le risque accru d’apparition de la dépression. Nous analysons d’un œil critique certains des mécanismes sous-jacents qui peuvent contribuer à l’augmentation de ce risque et nous accordons une attention spéciale aux événements qui se produisent pendant la transition vers la ménopause. Enfin, nous explorons certaines des répercussions cliniques et thérapeutiques de la dépression d’origine hormonale chez les femmes.

Medical subject headings: depression; estrogens; hormone replacement therapy; menopause; premenstrual syndrome; pregnancy.

Competing interests: Dr. Soares is a recipient of grant/research support from Eli Lilly, AstraZeneca, NARSAD and Physicians Services Incorporated. He is also a research consultant for GlaxoSmithKline, Wyeth, Forest, Lundbeck, Sepracor Inc. and Neurocrine. Dr. Soares is a part of the Speakers’ Bureau of GlaxoSmithKline, AstraZeneca, Wyeth, Forest, Berlex and Lundbeck. Dr. Soares did not receive any direct financial compensation for writing this manuscript. Dr. Zitek is an employee of Wyeth Research.

Acknowledgements: The authors thank Dennis Stancavish, MA, and Jennifer Hutcheson for their writing and editing assistance on this manuscript.

Contributors: Drs. Soares and Zitek conducted the literature review, wrote and reviewed the article and gave final approval for its publication.

Submitted June 25, 2007; Revised Nov. 19, 2007; Accepted Nov. 21, 2007

Correspondence to: Dr. C.N. Soares, Department of Psychiatry and Behavioral Neurosciences, McMaster University, 301 James St. S, FB#638, Hamilton ON L8P 3B6; fax 905 521-6098;