The Role of Hormones in Postpartum Mood Disorders

Phase 2

Completed

• Conditions: Postpartum Depression
• Interventions: Drug: Estradiol; Other: Placebo; Drug: Progesterone

• Registration Number: NCT00001481
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

Determine whether postpartum depression is triggered by the abrupt withdrawal of estrogen and progesterone.

The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major effective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estrogen and progesterone for an additional month. Outcome measures will include mood, behavioral and hormonal parameters (a separate protocol done in collaboration with NICHD).

Detailed Description

The appearance of mood and behavioral symptoms during pregnancy and the postpartum period has been extensively reported. While there has been much speculation about possible biologically based etiologies for postpartum disorders (PPD), none has ever been confirmed. Preliminary results from two related studies (protocols 90-M-0088, 92-M-0174) provide evidence that women with menstrual cycle related mood disorder, but not controls, experience mood disturbances during exogenous replacement of physiologic levels of gonadal steroids. The present protocol is designed to create a scaled-down hormonal milieu of pregnancy and the puerperium in order to determine whether women who have had a previous episode of postpartum major affective episode will experience differential mood and behavioral effects compared with controls and to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms. Supraphysiologic plasma levels of gonadal steroids will be established, maintained, and then rapidly reduced, simulating the hormonal events that occur during pregnancy and parturition. This will be accomplished by administering estradiol and progesterone to women who are pretreated with a gonadotropin releasing hormone (GnRH) agonist (Lupron). After eight weeks, administration of gonadal steroids will be stopped in one group of patients and controls, and a sudden decline in the plasma hormone levels will be precipitated. Another group will be maintained on supraphysiologic levels of estradiol and progesterone for an additional month. Outcome measures will include mood, behavioral, and hormonal parameters.

Study Timeline

• Study Start: 1996-04-26
• Study First Submitted: 1999-11-03
• Study First Submitted QC: 1999-11-03
• Study First Posted: 1999-11-04
• Primary Completion: 2024-10-25
• Study Completion: 2024-10-25
• Status Verified: 2025-01-15
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1, Hormone and Placebo Group	Placebo	8 weeks of hormonal addback plus 4 weeks of placebo
Group 1, Hormone and Placebo Group	Estradiol	8 weeks of hormonal addback plus 4 weeks of placebo
Group 1, Hormone and Placebo Group	Progesterone	8 weeks of hormonal addback plus 4 weeks of placebo
Group 2, Continued Replacement Group	Estradiol	12 weeks of hormone addback
Group 2, Continued Replacement Group	Progesterone	12 weeks of hormone addback

Primary Outcome Measures

Name	Time	Method
Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.	ongoing	Outcome measures will include mood, behavioral, and hormonal parameters as well as response to o-CRH.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States