Protocol Number: 04-M-0221

Title:

The Treatment of Menstrually-Related Mood Disorders with Extended Versus Interrupted Oral Contraceptives

Number:

04-M-0221

Summary:

This study will determine whether continuous administration of birth control pills over several menstrual cycles prevents the recurrence of menstrually related mood disorders (MRMD), which is a severe form of premenstrual syndrome (PMS). Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. This study will use various treatment regimens with birth control pills and placebo (sugar pill) to clarify the relationships among estrogen and progesterone, the menstrual cycle, and mood.

Healthy women between 18 and 45 years of age who menstruate may be eligible for this 15-week study. Candidates are screened with a physical examination, blood and urine tests, an electrocardiogram, and 3 months of symptoms ratings to confirm MRMD.

Participants are randomly assigned to one of three treatment groups. Group 1 takes a birth control pill every day and on three occasions takes a placebo capsule. Group 2 takes a birth control pill most but not all days and on three occasions takes a placebo capsule. Group 3 takes a birth control pill every day and on three occasions takes another medication called CDB-2914 that causes menstrual bleeding to occur.

Participants come to the NIH clinic every other week for blood tests and measurement of vital signs (blood pressure, pulse, and temperature) and to complete symptoms ratings scales. Subjects who develop breakthrough bleeding (menstruation earlier than expected) will have a transvaginal ultrasound. For this procedure, a probe is inserted into the vagina for about 10 minutes. The probe gives off and receives sound waves that can be used to form a picture of the endometrium (lining of the uterus).

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility Criteria:

INCLUSION CRITERIA:

Subjects will be recruited from the MRMD screening protocol, 81-M-0126.

Inclusion Criteria (are from protocol 81-M-0126 and are as follows):

-Subjects who meet criteria for MRMD are healthy (by physical exam, normal pelvic exam and pap smear, and normal lab values) and medication free will be included in this study.

-Oral contraceptives (and CDB-2914 in arm #3) will not be administered to any subject with significant clinical or laboratory abnormalities.

EXCLUSION CRITERIA:

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

Subjects taking psychotropic agents (e.g. antidepressants, anxiolytics or mood stabilizers) will likewise be excluded from the study.

Women who have received glucocorticoid or megesterol therapy within the last year (and thus may experience residual suppression of the compensatory HPA axis response to CDB-2914-induced glucocorticoid receptor antagonism) will be also excluded, albeit almost entirely on theoretical grounds.

Women who have any chronic medical conditions or are taking medications will be excluded.

Women who have a medical condition or are taking any medications that may increase serum potassium levels will also be excluded.

Those patients who would be uncomfortable with extending the length of their menstrual cycles will not be enrolled in this study and will either be offered participation in another study or an outside referral for treatment in the community.

The following conditions will constitute contraindications to treatment with continuous oral contraception or the use of the progesterone antagonist, CDB-2914, and will preclude a patient's participating in this protocol:

-history of endometriosis, or recent, rapid growth of uterine fibroid tumors (defined as doubling in size in six month period);

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

-hepatic disease as manifested by abnormal liver function tests;

-history of breast carcinoma;

-history of pulmonary embolism or phlebothrombosis;

-undiagnosed vaginal bleeding;

-porphyria;

-history of malignant melanoma;

-history of cholecystitis or pancreatitis;

-history of hypercholesterolemia, hypertension, diabetes, or renal disease;

-recurrent migraine headaches (greater than or equal to 3 per year) in women 25 or older;

-pregnancy or lactation;

-cigarette smoking in women 35 or older, or more than 10 cigarettes per day in women under 35; or

-use of oral, injectable, or inhaled glucocorticoids or megesterol with

Special Instructions: Currently Not Provided

Keywords:

Depression

Menstrual Cycle

Gonadal Steroids

Ethinyl Estradiol

Drospirenone

Recruitment Keywords:

Menstrual Cycle

Menstrually Related Mood Disorder

MRMD

Depression

Conditions:

Investigational Drug(s):

CDB 2914

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J. Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med. 1983 Dec;45(6):503-7. PMID: 6686333

Schmidt PJ, Nieman LK, Grover GN, Muller KL, Merriam GR, Rubinow DR. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. N Engl J Med. 1991 Apr 25;324(17):1174-9. PMID: 2011161

Muse KN, Cetel NS, Futterman LA, Yen SC. The premenstrual syndrome. Effects of "medical ovariectomy". N Engl J Med. 1984 Nov 22;311(21):1345-9. PMID: 6387488

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