Hormonal Causes of Menstrual-Related Mood Disorders

This study will explore possible hormonal causes of menstrual-related mood disorders (MRMD) by stopping the menstrual cycle with a drug called Lupron and then giving in sequence two menstrual cycle hormones, progesterone and estrogen. The study will first evaluate Lupron's effectiveness in treating MRMD and will then examine the effects of giving estrogen and progesterone on mood and behavior. In addition, positron emission tomography (PET) and magnetic resonance imaging (MRI) will be used to study serotonin receptors and transporters - molecules in the brain that are thought to play a major role in mood changes related to the menstrual cycle. Menstruating women between 18 and 50 years of age who are in good health, not pregnant, and not taking medications may be eligible for this study. Women with MRMD must have had at least moderately severe MRMD or behavioral disturbances for at least 6 months within 2 years of entering the study. Healthy controls must have no history of MRMD or behavioral disturbances. Candidates undergo physical and neurological examinations, chest x-ray, electrocardiogram, and blood and urine tests. Results of a recent Pap smear (no longer than 12 months before beginning the study) must be available. Participants undergo the following tests and procedures: * Drug treatment: Lupron is injected into a muscle once a month for 5 months. After the second month, participants receive estrogen or progesterone, or both, daily. Estrogen is delivered through a skin patch (20 micrograms per day) and the progesterone is taken as a rectal or vaginal suppository twice a day for the remaining 12 weeks of the study. Every day, all participants wear a skin patch and insert two suppositories, but at some point during the 12 weeks, active medication is replaced with placebo to allow the drugs to wash out of the body. * Physical examination and blood draw: A physical examination and blood tests are done at the start of the study and several times during the study to assess general health, evaluate liver and kidney function, and measure blood cell counts. * Response to treatment drugs: Responses to Lupron, estrogen, and progesterone are evaluated periodically with interviews and symptoms self-rating scales. Control subjects also take paper and pencil psychological tests. * PET imaging: A total of six PET scans are done at three time points during hormone treatment. PET uses small amounts of a radioactive chemical called a tracer that "labels" active areas of the brain. For the procedure, the subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed to help keep the subject's head still during the scan so the images will be clear. A brief scan is done just before the radioactive tracer is injected to help in analyzing the PET data. After the tracer is injected through a catheter (plastic tube) placed in the arm, pictures are taken for about 2 hours, during which the subject lies still on the scanner bed. * MRI scan: MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the patient lies on a table that is moved into the scanner (a narrow cylinder) and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The procedure lasts about 1 hour.