The Role of Hormones in Postpartum Mood Disorders

NCT ID: NCT00001481

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-04-26
• Study Completion Date: 2024-10-25

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.

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.

Conditions

Postpartum Depression

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Estradiol

Intervention Type: DRUG

Participants receive 17 beta-estradiol as oral capsule twice daily

Placebo

Intervention Type: OTHER

Participants receive placebo as oral capsule twice daily

Progesterone

Intervention Type: DRUG

Participants receive progesterone as oral capsule twice daily

leuprolide acetate

Intervention Type: DRUG

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

Interventions

Estradiol

Participants receive 17 beta-estradiol as oral capsule twice daily

Intervention Type: DRUG

Placebo

Participants receive placebo as oral capsule twice daily

Intervention Type: OTHER

Progesterone

Participants receive progesterone as oral capsule twice daily

Intervention Type: DRUG

leuprolide acetate

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

Intervention Type: DRUG

Other Intervention Names

Lupron

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter J Schmidt, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Mental Health (NIMH)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_1995-M-0097.html

NIH Clinical Center Detailed Web Page

Other Identifiers

95-M-0097

Identifier Type: -

Identifier Source: secondary_id

950097

Identifier Type: -

Identifier Source: org_study_id