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Updated: Jul 15, 2026

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Published on: December 2, 2015
[Sensitive to change: neuroendocrinologic aspects of depression in women]
L A M Kooiman1, B J A Jansen, F P M L Peeters
1Departement voor Medische, Klinische en Experimentele Psychopatologie, Universiteit Maastricht. lucia.kooiman@hotmail.com
Background:
Depression is more prevalent among women than among men. There are several possible explanations for this. There are indications that the aetiology of this difference in prevalence has to do with fluctuations in the oestrogen level, which are a feature of the female reproductive system. The influence of oestrogens on the hypothalamic-pituitary-adrenal axis may play an important role.
Aim:
To cast light on the deregulating influence of oestrogen on the hypothalamic-pituitary-adrenal axis. This deregulation could lead to depression in a subgroup of women with a neuroendocrine stress response that is sensitive to hormonal fluctuations.
Method:
PubMed was used to review the literature on the basis of the key words 'depression', 'estrogen', 'gender', 'gonadal hormones', 'hpa axis', 'stress' and 'women'.
Results:
Deregulation of the hypothalamic-pituitary-adrenal axis plays a role in the aetiology of major depression. On the one hand, oestrogens stimulate the activity of this system. On the other hand, a lowering of the endogenous oestrogen level seems to be accompanied by reduced activity of the hypothalamic-pituitary-adrenal axis.
Conclusion:
Changing oestrogen levels characterise the female reproductive system. It is these changing levels--not the absolute oestrogen level--which have the potential to deregulate the hypothalamic-pituitary-adrenal axis.
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