The Role of Hormones in Postpartum Mood Disorders

NCT00001481 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 95009795-M-0097
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The present protocol is designed to create a "scaled-down" hormonal milieu of pregnancy and the puerperium in order to determine whether it is the abrupt withdrawal of gonadal steroids or the prolonged exposure to gonadal steroids that is associated with mood symptoms.

Conditions

Postpartum Depression

Keywords

Postpartum Disorders; Mood; Hormones; GnRH Agonist; Postpartum Depression

Outcome Measures

Primary Outcomes (1)

• Edinburgh Postnatal Depression Scale (EPDS) Mean Total Score

  The Edinburgh Postnatal Depression Scale (EPDS) is a self-reported 10 item questionnaire to asses a participant's mood over the past week. Each question has four possible answers, scored from 0 to 3 with total score ranging from 0 to 30. Higher scores indicate more severe mood symptoms. EPDS was administered once every 2 weeks for the duration of the study. Analysis was calculated as the mean of scores for baseline (week 16) and weeks 18 and 20.

  Weeks 16, 18, and 20

Study Arms (6)

Arm 1a - Postpartum depression: Hormone withdrawal Group

EXPERIMENTAL

Female participants with history of postpartum depression (PPD) received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 15, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily. During weeks 16 through 20, all participants received placebo capsules to be taken twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Arm 1b - Depression, non-reproductive: Hormone withdrawal Group

EXPERIMENTAL

Female participants with history of non-reproductive related depression received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 15, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily. During weeks 16 through 20, all participants received placebo capsules to be taken twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Arm 1c- Healthy Volunteer: Hormone withdrawal Group

ACTIVE COMPARATOR

Female participants without history of depression received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 15, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily. During weeks 16 through 20, all participants received placebo capsules to be taken twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Arm 2a: Postpartum Depression; Hormone Continuation Group

EXPERIMENTAL

Female participants with history of postpartum depression (PPD) received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 20, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Arm 2b - Depression, non-reproductive: Hormone Continuation Group

EXPERIMENTAL

Female participants with history of non-reproductive related depression received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 20, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Arm 2c- Healthy Volunteer: Hormone Continuation Group

ACTIVE COMPARATOR

Female participants without history of depression received 3.75 mg of gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (Lupron) via intramuscular injection on a monthly basis for five months (20 weeks), administered during visit for weeks 0, 4, 8, 12, \& 16. Participants received oral capsules twice daily under single blind conditions for the same 5 months (20 weeks). During weeks 0 through 7, all participants received placebo via oral capsule twice daily. During weeks 8 through 20, all participants received 2 mg of 17 beta-estradiol via oral capsule twice daily and 200 mg of progesterone via oral capsule twice daily.

Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

Interventions

Estradiol DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Arm 1a - Postpartum depression: Hormone withdrawal Group; Arm 1b - Depression, non-reproductive: Hormone withdrawal Group; Arm 1c- Healthy Volunteer: Hormone withdrawal Group; Arm 2a: Postpartum Depression; Hormone Continuation Group; Arm 2b - Depression, non-reproductive: Hormone Continuation Group; Arm 2c- Healthy Volunteer: Hormone Continuation Group

Placebo OTHER

Participants receive placebo as oral capsule twice daily

Arm 1a - Postpartum depression: Hormone withdrawal Group; Arm 1b - Depression, non-reproductive: Hormone withdrawal Group; Arm 1c- Healthy Volunteer: Hormone withdrawal Group; Arm 2a: Postpartum Depression; Hormone Continuation Group; Arm 2b - Depression, non-reproductive: Hormone Continuation Group; Arm 2c- Healthy Volunteer: Hormone Continuation Group

Progesterone DRUG

Participants receive progesterone as oral capsule twice daily

Arm 1a - Postpartum depression: Hormone withdrawal Group; Arm 1b - Depression, non-reproductive: Hormone withdrawal Group; Arm 1c- Healthy Volunteer: Hormone withdrawal Group; Arm 2a: Postpartum Depression; Hormone Continuation Group; Arm 2b - Depression, non-reproductive: Hormone Continuation Group; Arm 2c- Healthy Volunteer: Hormone Continuation Group

leuprolide acetate DRUG

Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly

Also known as: Lupron

Arm 1a - Postpartum depression: Hormone withdrawal Group; Arm 1b - Depression, non-reproductive: Hormone withdrawal Group; Arm 1c- Healthy Volunteer: Hormone withdrawal Group; Arm 2a: Postpartum Depression; Hormone Continuation Group; Arm 2b - Depression, non-reproductive: Hormone Continuation Group; Arm 2c- Healthy Volunteer: Hormone Continuation Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A. Group 1: Women with a history of postpartum depression:
• A history of Diagnostic and Statistical Manual (DSM)-IV major depression or hypomanic/manic episode that occurred within three months of childbirth (as determined by a Structured Clinical Interview for the DSM (SCID) interview));
• has been well for a minimum of one year;
• a regular menstrual cycle for at least three months;
• age 18-50;
• not pregnant, not lactating and in good medical health;
• medication free (including birth control pills);
• no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.
• B. Group 2: Women with a history of Major Depressive Disorder
• A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum;
• has been well for a minimum of one year;
• a regular menstrual cycle for at least three months;
• age 18-50;
• not pregnant, not lactating and in good medical health;
• medication free (including birth control pills);

You may not qualify if:

• Patients will not be permitted to enter this protocol if they have important clinical or laboratory abnormalities including any history of the following:
• endometriosis;
• undiagnosed enlargement of the ovaries;
• liver disease;
• breast cancer;
• a history of blood clots in the legs or lungs;
• undiagnosed vaginal bleeding;
• porphyria;
• diabetes mellitus;
• malignant melanoma;
• gallbladder or pancreatic disease;
• heart or kidney disease;
• cerebrovascular disease (stroke);
• cigarette smoking;
• a history of suicide attempts or psychotic episodes requiring hospitalization;

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depression, Postpartum

Interventions

Estradiol; Progesterone; Leuprolide

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Peter Schmidt
• Organization: National Institute of Mental Health (NIMH)

peterschmidt@mail.nih.gov

+1 301 496 6120

Study Officials

• Peter J Schmidt, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: April 26, 1996
• Primary Completion: October 25, 2024
• Study Completion: October 25, 2024
• Last Updated: December 5, 2025
• Results First Posted: December 5, 2025

Record last verified: 2025-01-15

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 24 months after final publication
• Access Criteria: Data will be shared with dbGaP, Biomedical Translational Research Information System (BTRIS) and NIMH Data Archive as determined by the Principal Investigator.

Locations

US (1)