INCLUSION CRITERIA
Self-report the onset of depression associated with menstrual cycle irregularity or amenorrhea.
A current episode of minor (meeting 3-4 criterion symptoms) or major depression (of moderate severity or less on the SCID severity scale and not meeting DSM-IV criteria symptom 9 (suicide)) as determined by the administration of the minor depression module of the SADS-L and the Structured Clinical Interview for DSM-IV. Additionally, to ensure that subjects meet a minimum threshold for severity of depression, subjects will have scores greater than or equal to 10 on either the Beck Depression inventory (BDI) or the center for Epidemiologic Studies-Depression (CES-D) Scale during at least three of the four clinic visits during the month screening phase, as well as a 17 item Hamilton Depression score greater than or equal to 10.
Subjects will be excluded if they meet any of the following criteria: major depression of greater than moderate severity, DSM-IV criteria #9 (suicide), or anyone requiring immediate treatment after clinical assessment or functional impairment ratings of five or six for more than seven consecutive days on daily ratings.
Evidence of perimenopausal reproductive status.
Age 40 to 60.
No prior hormonal therapy for the treatment of perimenopause-related mood or physical symptoms with the last six months.
No history of psychiatric illness during the two years prior to the reported onset of the current episode of depression
In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins and calcium supplements).
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 reproductive status evaluated and documented.
Perimenopausal reproductive status will be defined by a history of least 6 months of menstrual cycle irregularity and biological evidence of ovarian dysfunction, specifically three of four plasma FSH values greater than 14 IU/L on consecutive occasions drawn at two-week intervals over a period of eight weeks (total of four blood samples).
Any subject with significant physical, EKG, or laboratory abnormalities, or who meets any of the exclusion criteria (listed below) will not participate in this protocol. Additionally, prior to participation all subjects will be examined for any contraindications to estrogen therapy. Women will be examined by a gynecologist of their choice and have evidence of a negative gynecologic exam within 12 months of initiation of this protocol.
EXCLUSION CRITERIA:
Severe major depression with any of the following:
Positive (threshold) response to SCID major depression, suicidal ideation;
Anyone requiring immediate treatment after clinical assessment;
Severity ratings greater than moderate on the SCID IV interview;
Functional impairment ratings of five or six for more than seven consecutive days on daily ratings.
Current treated with antidepressant medications.
History psychiatric illness during the two years before the reported onset of the current episode of depression.
History of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (those who smoke greater than 10 cigarettes per day); varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.
Renal disease, asthma.
Hepatic dysfunction.
Women with a history of carcinoma of the breast, or any women with a family history of the following: premenopausal breast cancer or bilateral breast cancer in a first-degree relative; multiple family members (greater than three relatives) with postmenopausal breast cancer.
Women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding.
Patients with a known hypersensitivity to raloxifene, phytoestrogens (including Rimostil, isoflavones, genistein, daidzein, red clover extract and soy-related compounds), estradiol, Alora, medroxyprogesterone acetate, or the excipients (inactive compounds) contained within these medications including: Rimostil- tocopherols, cellulose, calcium hydrogen phosphate, magnesium stearate, sillicalcolloidal anhydrous;
Provera- calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose, talc; Alora- sorbitan monooleate, acrylic adhesive; Evista- anhydrous lactose, carnauba wax, crospovidone, FD&C; blue #2 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.
Pregnant women.
Porphyria.
Diabetes mellitus.
Cholecystitis or pancreatitis.
History of cerebrovascular disease (stroke), epilepsy, hypertension,
hypercalcemia.
Recurrent migraine headaches.
Malignant melanoma.
History of familial hyperlipoproteinemia.