Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 50 Years
Eligible Sex
Female
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Basic Science
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron
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.
  • Drug: Estradiol
    Participants receive 17 beta-estradiol as oral capsule twice daily
  • Other: Placebo
    Participants receive placebo as oral capsule twice daily
  • Drug: Progesterone
    Participants receive progesterone as oral capsule twice daily
  • Drug: leuprolide acetate
    Leuprolide acetate is a gonadotropin releasing hormone (GnRH) agonist, given via intramuscular injection monthly
    Other names:
    • Lupron

More Details

Status
Completed
Sponsor
National Institute of Mental Health (NIMH)

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.