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Giovanni Cizza, Philip W. Gold, George P. Chrousos, High-Dose Transdermal Estrogen, Corticotropin-Releasing Hormone, and Postnatal Depression, The Journal of Clinical Endocrinology & Metabolism, Volume 82, Issue 2, 1 February 1997, Page 704, https://doi.org/10.1210/jcem.82.2.3771-5
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A.J.P. Gregoire et al. recently reported in The Lancet that high-dose transdermal estrogen is an effective treatment for postnatal depression (1). In this double-blind, placebo-controlled study, a 3-month course of 200 μg/day of 17β-estradiol significantly improved the clinical symptomatology of severely depressed women within 1 month of treatment; its antidepressant effect lasted over 5 months.
Although the etiology of the postnatal “blues” and its more severe form, postnatal depression, is not known, several endocrine mechanisms have been proposed. We have hypothesized that these conditions may be caused by transient hypoactivation of the hypothalamic corticotropin-releasing hormone (CRH) neurons of varying degree and duration (2). This hypoactivation may be the combined result of glucocorticoid-induced suppression and estrogen deficiency.
The third trimester of pregnancy is characterized by a hyperactive hypothalamic-pituitary-adrenal (HPA) axis. This is the result of progressively increasing levels of circulating CRH of placental origin and decreasing levels of CRH-binding protein, both phenomena contributing to elevated levels of bioactive “free” CRH and, thus, hypersecretion of ACTH and cortisol (3). In addition, the elevated serum estradiol levels of pregnancy may participate in the stimulation of the HPA axis during this period (4). After delivery of the fetus and placenta, the source of CRH and estradiol is removed, and the HPA axis depends upon hypothalamic CRH secretion to maintain its activity. However, exposure to high concentrations of endogenous or exogenous glucocorticoids for more than 2 weeks has been associated with an impairment of adrenocortical function, whose central locus resides at the level of the hypothalamic CRH neuron and its higher inputs (5). This, together with postnatal estrogen deficiency, leads to a state of hypoactivation of the HPA axis, which may last from a few weeks to several months. We recently demonstrated that, indeed, in the subgroup of women who develop the postnatal blues or depression, the suppression of the HPA axis is more severe and lasts longer than that of women who have no emotional problems in the postpartum period (2). The mean plasma ACTH response to an iv bolus of 1 μg/kg of ovine (o) CRH was more severely blunted. This attenuation lasted for a longer period of time (at least 12 weeks vs. 3 weeks) in depressed than in euthymic women, suggesting a more pronounced and sustained suppression of the hypothalamic CRH neuron in this subgroup of patients (2).
