Protocol Number: 00-M-0103

Title:

The Treatment of Menstrually-Related Mood Disorders with Continuous Gonadal Steroid Replacement

Number:

00-M-0103

Summary:

This study investigates the effects on symptoms of combined treatment with estrogen and progesterone in women with severe premenstrual syndrome (PMDD).

Studies indicate that women with PMS experience improvement in symptoms following treatment with leuprolide acetate, when estrogen and progesterone levels are low. Women with PMS, but not women without the disorder, experience a return of symptoms within approximately a week after re-exposure to either estrogen or progesterone. The cause of this hormone-induced depression remains unclear. It is not known whether this depressed mood is due simply to the change in the levels of estrogen and progesterone and whether it would remit following continued exposure to stable levels of estrogen and progesterone. This study will determine whether the maintenance of stable hormone levels will prevent mood disturbances in women with PMS.

Participants in this study will receive leuprolide acetate injections once a month for up to 6 months. After 2 months, women whose symptoms have improved will receive a skin patch containing either estrogen or placebo (an inactive substance) and will be asked to take daily suppositories containing either progesterone or placebo. Women whose symptoms of PMS do not respond to leuprolide treatment after 2 months will end the study and be offered other treatment. Participants will be seen by a nurse in the clinic every two weeks and will fill out ratings and have blood drawn to measure hormone levels.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility Criteria:

INCLUSION CRITERIA:

The subjects of this study will be women who meet the criteria for MRMD as described in Protocol # 81-M-0126, The Phenomenology and Biophysiology of Menstrually-related Mood and Behavioral Disorders. In brief, these criteria include the following:

1) history within the last two years of at least six months with menstrually-related mood or behavioral disturbances of at least moderate severity--i.e., disturbances that are distinct in appearance and associated with a notable degree of subjective distress and interference with life activities;

2) symptoms with a sudden offset and absence of significant symptomatology during the follicular phase;

3) age 18-50;

4) regular menstrual cycles (21-35 days in length), not pregnant, and in good medical health;

5) medication free.

All patients participating in this protocol will have already participated in Protocol No. 81-M-0126 and will have a prospectively confirmed and predictable relationship between their mood disorder and the premenstrual phase of the menstrual cycle; i.e., a 30% change in severity of symptom self rating scales, relative to the range of the scale employed, during the seven days premenstrually compared with the seven days post-menstrually in two out of three months of study. This method formed the basis of the NIMH PMS Workgroup diagnostic guidelines and produces results that are highly convergent with the effect size method for diagnosing PMS.

All subjects will be required to use non-hormonal forms of birth control (e.g. barrier methods with the exception of IUD's) to avoid pregnancy during this study.

EXLUSION CRITERIA:

Any patient with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

Subjects taking birth control pills or psychotropic agents (e.g. antidepressants, anxiolytics or lithium carbonate) will be excluded from the study.

The following conditions, also, will constitute contraindications to treatment with hormonal therapy and will preclude a patient's participating in this protocol:

1) history of endometriosis;

2) diagnosis of ill-defined, obscure pelvic lesions, particularly undiagnosed ovarian enlargement;

3) hepatic disease as manifested by abnormal liver function tests;

4) history of breast carcinoma;

5) history of pulmonary embolism or phlebothrombosis;

6) undiagnosed vaginal bleeding;

7) porphyria;

8) history of malignant melanoma;

9) history of cholecystitis or pancreatitis;

10) history of cardiovascular or renal disease;

11) pregnancy.

Special Instructions:

Call referral contact for additional eligibility criteria.

Keywords:

Depression

Menstrual Cycle

Gonadal Steroids

GnRH Agonist

PMS

Estradiol

Progesterone

Mood

MRMD

PMDD

Recruitment Keyword(s):

Menstrually Related Mood Disorders

Condition(s):

Premenstrual Syndrome

Depression

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Depot Leuprolide Acetate

Supporting Site:

National Institute of Mental Health

Contact(s):

Linda Simpson-St. Clair, R.N.
National Institutes of Health
Building 10
Room 3N238
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 496-9576
Fax: (301) 402-2588
Electronic Address: simpsonl@irp.nimh.nih.gov

Citation(s):

Changes in plasma hormones across the menstrual cycle inpatients with menstrually related mood disorder and in control subjects

Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome

Lack of effect of induced menses on symptoms in women with premenstrual syndrome

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