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.
PMID 10831472 10831472 DOI 10.1176/appi.ajp.157.6.924 10.1176/appi.ajp.157.6.924 Bloch et al. 2000, Bloch 2000
Cite this article
Bloch, M., Schmidt, P. J., Danaceau, M., Murphy, J., Nieman, L., & Rubinow, D. R. (2000). Effects of gonadal steroids in women with a history of postpartum depression. The American journal of psychiatry, 157(6), 924-930. https://doi.org/10.1176/appi.ajp.157.6.924
Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. Am J Psychiatry. 2000;157(6):924-930. doi:10.1176/appi.ajp.157.6.924
Bloch, M., et al. "Effects of gonadal steroids in women with a history of postpartum depression." The American journal of psychiatry, vol. 157, no. 6, 2000, pp. 924-930.
The postpartum period is a time when women are vulnerable to depressive disorders, which can be severe and have long-lasting adverse sequelae. In spite of multiple contacts with health care providers, women with postpartum depression often remain unrecognized and untreated. To evaluate the association between estradiol and postpartum depression, we measured serum estradiol concentration and performed an open-label study of physiologic 17beta-estradiol. Twenty-three women fulfilling ICD-10 criteria for major depression with postpartum onset were consecutively recruited from a psychiatric emergency unit. Serum estradiol concentrations were measured at baseline and weekly during sublingual 17beta-estradiol treatment for 8 weeks. The treatment effect was assessed using a clinician-rated depression symptom scale, the Montgomery-Asberg Depression Rating Scale (MADRS). At baseline, all patients were severely depressed (mean MADRS total score = 40.7; range, 35-45) and had a low serum estradiol concentration (mean = 79.8 pmol/L; range, 23-140 pmol/L); in 16/23 patients, the concentration was even lower than the threshold value for gonadal failure. During the first week of estradiol treatment, depressive symptoms diminished significantly, resulting in a mean MADRS score of 11.0 (Z = -4.20, p < .001), and serum estradiol concentrations approached those of the follicular phase (mean +/- SD = 342 +/- 141 pmol/L). At the end of the second week of treatment, the MADRS scores were compatible with clinical recovery in 19/23 patients. This preliminary study shows that depression symptoms may be rapidly reduced in patients with postpartum depression who have documented estradiol deficiency by treatment with 17beta-estradiol and suggests that estradiol can have significance in the pathophysiology of this condition and may be an option in the treatment of women vulnerable to postpartum depression.
Cycle Across the Lifespan · Cycle and General Health
Bouchard TP et al., 2026·Journal of ovarian research·
Open Access
Reproductive hormones of the fertile window are often referenced to women in regular cycles, but this may not be representative of the hormonal profiles of women in different circumstances like polycystic ovarian syndrome, the postpartum period, and the perimenopause transition. This observational cohort study sought to identify the variability in the reproductive hormones in various clinical circumstances and to establish potential thresholds for each category based on hormone measurements with the Mira urinary hormone monitor. A total of 57 women (ages 22-51) in various circumstances (regular cycles, polycystic ovarian syndrome, postpartum and perimenopause) tracked Mira urine hormone measurements (estrone-3-glucuronide, luteinizing hormone, pregnanediol glucuronide), contributing 444 cycles of data. Using additive mixed models, hormone values were stratified by the four different reproductive categories. The perimenopause and polycystic ovarian syndrome groups demonstrated relative hypoestrogenic states, while the perimenopause group showed low luteal pregnanediol glucuronide and the polycystic ovarian syndrome/polyendocrine metabolic ovarian syndrome (PCOS/PMOS) group showed high luteal pregnanediol glucuronide. The perimenopause group had significantly higher luteinizing hormone values throughout the whole cycle. The fertile window hormone thresholds vary depending on a woman's specific reproductive category. Women in different circumstances should not necessarily use the same hormonal thresholds for the fertile window and ovulation. A larger dataset with ultrasound correlation to ovulation is required to delineate the fertile window with more precision. Hormone differences across the menstrual cycle could be used for targeted treatments in polycystic ovarian syndrome and perimenopause women.
Anti-Müllerian hormone (AMH), produced by ovarian granulosa cells, is a key regulator of female reproduction. Traditionally seen as a local follicular brake, emerging evidence calls for a paradigm shift. We propose that AMH acts as a context-dependent signaling hub. It primarily signals via the Smad1/5/8 pathway and interacts with Wnt/β-catenin and MAPK cascades to regulate follicle growth and steroidogenesis. Beyond the ovary, AMH and its receptors are expressed in the hypothalamus, pituitary, uterus, and placenta, modulating the hypothalamic-pituitary-gonadal axis and other reproductive processes. This review provides a comprehensive framework for understanding AMH as a context-dependent signaling hub in female mammals.
Sajjad MU et al., 2026·Archives of gynecology and obstetrics
The human placenta consumes, on average, one third of the glucose from maternal blood. However, the role of placental glucose consumption in the production of estradiol and progesterone remains unclear. We hypothesized that placental glucose consumption in humans is associated with steroid production via a non-glycolytic pathway. We included 41 healthy pregnancies at term. Blood samples were obtained from the maternal radial artery, uterine vein, and from the umbilical artery and vein during scheduled cesarean delivery. Blood flow in the uterine artery and umbilical vein was measured using Doppler ultrasound. Plasma concentrations of estradiol, progesterone, glucose, insulin, lactate, and ketones were analyzed. We calculated uteroplacental uptake and consumption of maternal glucose and ketones, and the loss of uteroplacental lactate in 6-carbon units as well as the release of steroid hormones into maternal circulation. Our data revealed a net placental release of estradiol and progesterone into maternal circulation [24.1 (5.34, 49.8) and 560.3 (61.2, 798.2) nmol/min, respectively]. The release of estradiol was positively associated with uteroplacental glucose uptake (ρ = 0.59, p < 0.001) and consumption (ρ = 0.43, p = 0.005), while progesterone exhibited similar associations (ρ = 0.61, p < 0.001; ρ = 0.43, p = 0.005). Notably, both hormones correlated positively with lactate-adjusted uteroplacental glucose consumption but not with acetate-equivalent uteroplacental ketone consumption. Placental release of estradiol and progesterone correlates with uteroplacental consumption of glucose that primarily occurs via non-glycolytic pathways in the third trimester placenta.