The Role of Hormones in Postpartum Mood Disorders

NCTNCT00001481Other id950097Other id95-M-0097

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Overview

Status: Completed
Phase: Phase 2
Enrollment: 74 participants (actual)
Sponsor: National Institute of Mental Health (NIMH) · Nih
Design: Not randomized · Double masking
Countries: 1 country
United States
Start: 26 Apr 1996
Primary completion: 25 Oct 2024
Completion: 25 Oct 2024
First posted: 4 Nov 1999 (estimated)
Last update posted: 5 Dec 2025
Conditions: Postpartum Depression

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

200020052010201520202025

Ph 2
The Role of Hormones in Postpartum Mood Disorders
NCT00001481
26 Apr 1996 to 25 Oct 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

EstradiolDrug
PlaceboOther
ProgesteroneDrug
leuprolide acetateDrug

Arms6

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

Primary outcomes1

Outcomes the sponsor listed as primary.

Edinburgh Postnatal Depression Scale (EPDS) Mean Total Score
Time frame · Weeks 16, 18, and 20
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Weeks 16, 18, and 20

Edinburgh Postnatal Depression Scale (EPDS) Mean Total Score

Group	Value (Units on a scale)	Spread
Arm 1a - Postpartum Depression: Hormone Withdrawal	3.75	6.32
Arm 1b - Depression, Non-reproductive: Hormone Withdrawal	3	NA
Arm 1c - Healthy Volunteer: Hormone Withdrawal	0	0
Arm 2a - Postpartum Depression: Hormone Continuation	1.14	1.07
Arm 2b - Depression, Non-reproductive: Hormone Continuation	0.5	0.71
Arm 2c - Healthy Volunteer: Hormone Continuation	0.67	1.21

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Arm 1a - Postpartum Depression: Hormone WithdrawalFemale 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.	0 / 16	0 / 16	3 / 16
Arm 1b - Depression, Non-reproductive: Hormone WithdrawalFemale 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.	0 / 1	0 / 1	0 / 1
Arm 1c - Healthy Volunteer: Hormone WithdrawalFemale 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.	0 / 13	0 / 13	0 / 13
Arm 2a - Postpartum Depression: Hormone ContinuationFemale 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.	0 / 7	0 / 7	1 / 7
Arm 2b - Depression, Non-reproductive: Hormone ContinuationFemale 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.	0 / 2	0 / 2	0 / 2
Arm 2c - Healthy Volunteer: Hormone ContinuationFemale 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.	0 / 7	0 / 7	1 / 7

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: Female
Age: from 18 Years up to 50 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

* INCLUSION CRITERIA: A. Group 1: Women with a history of postpartum depression: 1. 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)); 2. has been well for a minimum of one year; 3. a regular menstrual cycle for at least three months; 4. age 18-50; 5. not pregnant, not lactating and in good medical health; 6. medication free (including birth control pills); 7. no history of puerperal suicide attempts or psychotic episodes requiring hospitalization. B. Group 2: Women with a history of Major Depressive Disorder 1. A history of DSM-IV major depression episode(s) occurring outside of pregnancy and not within three months postpartum; 2. has been well for a minimum of one year; 3. a regular menstrual cycle for at least three months; 4. age 18-50; 5. not pregnant, not lactating and in good medical health; 6. medication free (including birth control pills); 7. no history of suicide attempts or psychotic episodes requiring hospitalization. C. Group 3: Normal Controls 1\) Controls will meet all criteria specified except they must not have any past or present Axis I diagnosis or evidence of menstrual related mood disorders. EXCLUSION CRITERIA: 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; * recurrent migraine headaches; * pregnancy (patients will be warned not to become pregnant during the study and will be advised to employ barrier contraceptive methods; * pregnancy-related medical conditions such as hyperemesis gravidarum, pretoxemia and toxemia, deep vein thrombosis (DVT) and bleeding diathesis; * Any woman with a first degree relative (immediate family) with premenopausal breast cancer or breast cancer presenting in both breasts or any woman who has multiple family members (greater than three relatives) with postmenopausal breast cancer will also be excluded from participating in this protocol; * Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for the perimenopause will be excluded from participation. Specifically, we will exclude any woman with an elevated plasma follicle stimulating hormone (FSH) level (greater than or equal to 14 IU/L) and with menstrual cycle variability of \> 7 days different from their normal cycle length; * Subjects who are unable to provide informed consent; * National Institute of Mental Health (NIMH) employees and staff and their immediate family members will be excluded from the study per NIMH policy.

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