Effects of gonadal steroids in women with a history of postpartum depression

Objective: Endocrine factors are purported to play a role in the etiology o f postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of p ostpartum depression. Method: The supraphysiologic gonadal steroid levels of pregnancy and withdr awal from these high levels to a hypogonadal state were simulated by induci ng hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leup rolide acetate, adding back supraphysiologic doses of estradiol and progest erone for 8 weeks, and then withdrawing both steroids under double-blind co nditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales. Results: Five of the eight women with a history of postpartum depression (6 2.5%) and none of the eight women in the comparison group developed signifi cant mood symptoms during the withdrawal period, analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed signi ficant phase-by-group, effects. These effects reflected significant increas es in depressive symptoms in women with a history of postpartum depression hut not in the comparison group after hormone withdrawal (and during the en d of the hormone replacement phase), compared with baseline. Conclusions: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.