Sensitivity To Endogenous Hormones In Post-Partum Depression
Sensitivity To Endogenous Hormones In Post-Partum Depression
Abstract & Commentary
Source: Bloch M, et al. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry 2000;157:924-930.
It is estimated that postpartum depression (ppd) occurs in 10-15% of all childbirths. Although it is widely believed that fluctuations in gonadal hormones occurring during pregnancy and child birth play a major role in the etiology of postpartum depression, studies examining this association have yielded few consistent findings.
The objective of this study was to evaluate the role of the gonadal hormones’ estrogen and progesterone in the pathophysiology of postpartum depression. Under double-blind conditions, physiological states similar to those found in pregnancy and the postpartum were pharmacologically induced in euthymic women with and without a history of postpartum depression. Bloch and colleagues hypothesized that the abrupt discontinuation of high-dose estrogen and progesterone would precipitate depressive symptoms in women with a history of postpartum depression, but not in women without a history of postpartum depression.
Euthymic, unmedicated females, age 22-45, who were at least one year past their most recent childbirth were eligible for the study. Subjects were divided into two groups: the PPD-positive group consisted of eight women with at least one previous episode of postpartum depression and no previous episodes of nonpeurperal depression, and the PPD-negative group consisted of eight women with no history of psychiatric illness.
Following an eight-week screening phase, all subjects received leuprolide acetate to induce a baseline hypogonadal state; injections were continued at monthly intervals thereafter for four months. One month after the initial leuprolide injection, subjects received high-dose oral micronized estradiol and progesterone for eight weeks to simulate the hormonal conditions of pregnancy. Estradiol and progesterone were then abruptly discontinued, causing a precipitous drop in hormone levels that simulated the hormonal events of the postpartum period. Sub-
jects were followed for 12 weeks following hormone withdrawal. Mood was assessed at two-week intervals using the modified Cornell Dysthymia Scale which was performed by blinded raters. Subjects completed self ratings of mood and physical symptoms on a daily basis and the Beck Depression Inventory (BDI) and the Edinburgh Postnatal Depression Scale (EDRS) at two-week intervals.
A four-week period from each study phase was selected for analysis. Outcome measures were the means of the self and standardized assessments for each analysis period. For the modified Cornell Dysthymia Scale assessments, clinically significant symptomatology was defined as an increase from a baseline score greater than 12.
Eight women with a history of postpartum depression
and eight control subjects completed the study. Based on the modified Cornell Dysthymia Scale, five of the eight women (62.5%) with a history of PPD and none of the eight women without a history of PPD developed clinically significant mood symptoms during the hormone withdrawal period (P = 0.03). Based on the BDI and EDRS, small but statistically significant increases in symptom severity and mean rating scores compared to baseline were observed during the hormone withdrawal period in the PPD-positive women, compared to the PPD-negative women (P < 0.01). No group differences in plasma estradiol or progesterone levels were observed during the high-dose hormone or withdrawal periods.
COMMENT BY Ann M. Callahan, MD
Bloch et al present an interesting study that provides direct evidence supporting a role for the gonadal hormones estrogen and progesterone in the pathophysiology of postpartum depression. Despite the study’s small sample size, the fact that five out of eight PPD-positive women vs. zero out of eight PPD-negative women developed clinically significant depressive symptoms following high-dose hormone withdrawal is impressive. The importance of these findings is highlighted by the fact that no previous study has found an association between these hormones and the development of postpartum depres sion
Bloch et al conclude that a differential sensitivity to fluctuations in gonadal hormones may exist in the subgroup of women who experience postpartum depression. In addition, they also note that depressive symptoms occurred in the PPD-positive women, but not the PPD-negative women, despite the fact that no group differences in hormone levels were observed. This finding is consistent with earlier studies, and suggests that the development of postpartum depression is not associated with deranged hormone levels, but rather appears to develop in the context of physiologically "normal" perturbations in gonadal hormones.
A few limitations exist that deserve mention. First, the group sizes in this study were quite small. However, a significant effect of group and phase was seen with respect to the only blinded assessment (modified Cornell Dysthymia Scale), reflecting clinically significant symptoms in the PPD-positive group and a complete lack of symptoms in the PPD-negative group. Second, although the differences in mean rating scores between PPD-positive and PPD-negative women for the BDI and the EDPS were statistically significant, these scores were not indicative of impressive clinical symptomatology. Despite these limitations, this is an intriguing study that brings us closer to an understanding of the complex factors involved in the etiology of postpartum depression. (Dr. Callahan is the former chief of Clinical Psychopharmacology, Brown University Veterans Affairs Medical Center, Providence, RI).
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