Combined Hormone Replacement in Menstrually-Related Mood Disorders

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.