Completed

Hormonal Effects on Postpartum Mood Disorders

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Study Aim

This study aims to evaluate how hormonal changes affect mood disorders in new mothers by measuring mood symptoms using a questionnaire over several weeks.

What is being tested

Estradiol

+ Placebo

+ Progesterone

DrugOther
Who is being recruted

Urogenital Diseases+5

+ Mental Disorders

+ Depressive Disorder

From 18 to 50 Years
See all eligibility criteria
How is the trial designed

Basic Science Study

Phase 2
Interventional
Study Start: April 1996
See protocol details

Summary

Principal SponsorNational Institute of Mental Health (NIMH)
Last updated: December 5, 2025
Sourced from a government-validated database.Claim as a partner

Study start date: April 26, 1996

Actual date on which the first participant was enrolled.

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.

NCT00001481
Principal SponsorNational Institute of Mental Health (NIMH)
Last updated: December 5, 2025
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

74 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Basic Science Study

Basic science studies help researchers understand how the body works or how a disease develops. They don't test treatments, but they build the foundation for future therapies.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Female

Biological sex of participants that are eligible to enroll.

From 18 to 50 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Urogenital DiseasesMental DisordersDepressive DisorderFemale Urogenital Diseases and Pregnancy ComplicationsPregnancy ComplicationsPuerperal DisordersMood DisordersDepression, Postpartum

Criteria

INCLUSION CRITERIA: 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); 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.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

6 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

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.

Group II

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.

Group III

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.

Group IV

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.

Group 5

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.

Group 6

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.

Study Objectives

Primary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

National Institutes of Health Clinical Center

Bethesda, United StatesOpen National Institutes of Health Clinical Center in Google Maps
CompletedOne Study Center