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Postpartum DepressionPhase 2NCT00001481

The Role of Hormones in Postpartum Mood Disorders

A Phase 2 study testing Estradiol, Progesterone and leuprolide acetate in people with Postpartum Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 years, women only
Conditions the study is for
Postpartum Depression
What is being tested?
Estradiol, Progesterone and leuprolide acetate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
74 participants
Where
1 siteUnited States
Study dates
26 Apr 1996to 25 Oct 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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;
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  • medication free (including birth control pills);
  • no history of puerperal suicide attempts or psychotic episodes requiring hospitalization.
  • 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);
  • no history of suicide attempts or psychotic episodes requiring hospitalization.
  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: An Endocrine Model for Postpartum Mood Disorders

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.

Read the 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. 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 during ovarian hormone exposure and/or withdrawal 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.

Being tested
Estradiol, Placebo, Progesterone, leuprolide acetate
Keywords
Postpartum Disorders, Mood, Hormones, GnRH Agonist, Postpartum Depression
Medical subject headings
Depression, Postpartum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EstradiolDrug

    Participants receive 17 beta-estradiol as oral capsule twice daily

  • PlaceboOther

    Participants receive placebo as oral capsule twice daily

  • ProgesteroneDrug

    Participants receive progesterone as oral capsule twice daily

  • leuprolide acetateDrug

    Also called Lupron

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

Study groups in NCT00001481
Study groupRoleWhat they receive
Arm 1a - Postpartum depression: Hormone withdrawal GroupExperimentalFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate
Arm 1b - Depression, non-reproductive: Hormone withdrawal GroupExperimentalFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate
Arm 1c- Healthy Volunteer: Hormone withdrawal GroupActive comparatorFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate
Arm 2a: Postpartum Depression; Hormone Continuation GroupExperimentalFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate
Arm 2b - Depression, non-reproductive: Hormone Continuation GroupExperimentalFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate
Arm 2c- Healthy Volunteer: Hormone Continuation GroupActive comparatorFemale 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.
Receives: Drug: Estradiol; Other: Placebo; Drug: Progesterone; Drug: leuprolide acetate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Weeks 16, 18, and 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 1999 (estimated)
  2. Study start26 Apr 1996
  3. Primary completion25 Oct 2024
  4. Study completion25 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
74 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001481
Sponsor's protocol ID
950097
Other IDs
95-M-0097
Status last verified
15 Jan 2025
First submitted
3 Nov 1999
Last updated
5 Dec 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data will be shared with dbGaP, BTRIS and NIMH Data Archive as determined by the Principal Investigator.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Estradiol, Progesterone and leuprolide acetate in people with Postpartum Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Edinburgh Postnatal Depression Scale (EPDS) Mean Total Score (time frame: Weeks 16, 18, and 20). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.

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