The Effects of Estrogen Withdrawal on Mood Symptoms in Women

INCLUSION CRITERIA: All subjects for this protocol will be either self-referred in response to newspaper advertisements or referred by their personal physician. The women participating in this protocol will have previously completed the screening protocol # 88-M-0131 and, therefore, will have had the presence or absence of perimenopausal or menopausal reproductive status evaluated and documented. Women with a past perimenopause-related depression (within 12 years) and whose depression responded to ET will be recruited to participate in this randomized, parallel-design, double-blind, placebo-controlled study. Women with histories of either perimenopausal depression that was not responsive to ET or hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement will be excluded. The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by Structured Clinical Interview for DSM-IV (SCID) or Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), respectively) at midlife in association with menstrual cycle irregularity and the history of remission (also confirmed by SCID or SADS-L) of this depression after ET. Additionally, all women will report that they were placed on HRT for the treatment of perimenopausal symptoms, including depression. Age 45 to 65 In good medical health <TAB> Women without past perimenopausal depression - To control for the effects of the hormonal manipulations in this protocol, we will also recruit a group of asymptomatic controls who are either currently on ET or were prescribed ET previously and with no previous history of perimenopause-related depression or HRT-induced dysphoria. Women who participate in this study as the asymptomatic comparison group will meet the following criteria: Women who received hormone therapy (HT) with no previous history of perimenopause-related depression or HT-induced dysphoria No current mood or behavioral problems Age 45 to 65 In good medical health EXCLUSION CRITERIA: past history of severe major depression with suicidal ideation current treatment with antidepressant medications history of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis renal disease hepatic dysfunction women with a history of carcinoma of the breast women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding pregnant women cerebrovascular disease (stroke) recurrent migraine headaches