Effects of gonadal steroids in women with a history of postpartum depression
Abstract
OBJECTIVE: Endocrine factors are purported to play a role in the etiology of 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 postpartum depression. METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. 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 (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end 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.
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Post-birth decompensation in women with bipolar disorder is caused by genetic factors and by massive gonadal steroid withdrawal after birth in women who are neurobiologically sensitive to hormonal change.
“The causes of post-birth decompensation in women with bipolar disorder include genetic factors [31–33] and massive gonadal steroid withdrawal after birth in women who are neurobiologically sensitive to hormonal change [34].”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [34]
Women who develop postpartum onset major depression are differentially sensitive to the mood-destabilising effects of reproductive hormone withdrawal at birth.
“Women who develop postpartum onset major depression are differentially sensitive to the mood-destabilising effects of withdrawal from reproductive hormones at birth.”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [34]
In a landmark study, Bloch et al. simulated birth-related hormone withdrawal by inducing a hypogonadal state with leuprolide, adding back supraphysiologic oestradiol and progesterone for 8 weeks, then withdrawing both steroids under double-blind conditions; five of eight women with a history of postpartum depression developed mood symptoms, compared with none of eight women without such a history,
“In a landmark study, Bloch et al. [34] simulated the withdrawal of hormones at birth by inducing a hypogonadal state in women with leuprolide, adding back supraphysiologic doses of oestradiol and progesterone for 8 weeks, then withdrawing both steroids under double-blind conditions. Five of eight women with a history of postpartum depression, compared with 0 of the 8 women without a history of”
From Perinatal mental illness: Definition, description and aetiology (2014) · cites this paper as [34]
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- Authors
- Bloch, M., Schmidt, P. J., Danaceau, M., Murphy, J., Nieman, L., & Rubinow, D. R.
- Affiliations
- National Institutes of Health (US)
- Venue
- American Journal of Psychiatry
- Published
- 2000-06-01
- Volume
- 157
- Issue
- 6
- Pages
- 924-930
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2172024505
- Cited by
- 950
- References
- 26
- Citations by year
- 2026: 38 · 2025: 42 · 2024: 49 · 2023: 34 · 2022: 47 · 2021: 55 · 2020: 47 · 2019: 51 · 2018: 41 · 2017: 44 · 2016: 41 · 2015: 48 · 2014: 58 · 2013: 42 · 2012: 28
- FWCI
- 16.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- postpartum depression, sex steroids, estrogen, progesterone, hypogonadism, leuprolide, estradiol, progesterone withdrawal, mood symptoms, reproductive hormones
- MeSH terms
- Adult, Affect, Cross-Sectional Studies, Estradiol, Female, Humans, Hypogonadism, Middle Aged, Personality Inventory, Placebos, Progesterone, Psychiatric Status Rating Scales, Substance Withdrawal Syndrome, Leuprolide, Depression, Postpartum, Mood Disorders
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