INCLUSION CRITERIA:
Subjects for this study will meet the following criteria:
Women with a recent (within the last 12 years) past history of perimenopause-related depression and whose depression responded to ET will be recruited to participate in this randomized, parallel-design, double-blind, placebo-controlled study. The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by SCID or SADS-L, respectively) at midlife 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. To control for the effects of the hormonal manipulations in this protocol, we will also recruit a group of asymptomatic controls on ET and with no previous history of perimenopause-related depression or HRT-induced dysphoria.
Age 45 to 60;
In good medical health.
The women participating in this protocol will have their reproductive status evaluated and documented. Perimenopausal reproductive status will be defined by a history of at least 6 months of menstrual cycle irregularity and biological evidence of ovarian dysfunction, specifically three of four plasma FSH values greater than 14IU/L on consecutive occasions drawn at two week intervals over a period of eight weeks (total of four blood samples.)
During the initial screening period, a complete history, physical examination, and EKG will be performed on all subjects, and the following lab data will be obtained:
Blood-complete blood count; electrolytes; glucose, BUN and creatinine; liver function tests; thyroid function tests, prolactin, and lipid profile.
Urine-urinalysis; plasma beta HCG pregnancy test.
Any subject with significant physical, EKG, or laboratory abnormalities, or who meets any of the exclusion criteria will not participate in this protocol. Additionally, prior to participation all subjects will be examined for any contraindications to ET. Women will be examined by a gynecologist of their choice.
EXCLUSION CRITERIA:
Women with histories of either perimenopausal depression that are 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 following will constitute contraindications to participate in this protocol:
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
Warren Grant Magnuson Clinical Center (CC)