• INCLUSION CRITERIA:

Subjects for this study will meet the following criteria:

1. A history of at least two weeks with postpartum-related mood disturbances of moderate severity, and self-report of the onset of depression within three months of a normal vaginal delivery or uncomplicated Caesarean section;
2. 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 [suicidal ideation]) 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 six clinic visits during the two week 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 (including postpartum psychosis). DSM-IV criteria #9 (suicidal ideation), or anyone requiring immediate treatment after clinical assessment.
3. Not greater than six months post delivery;
4. Age 20 to 45;

5.) No prior hormonal therapy for the treatment of postpartum-related mood or physical symptoms within the last six months;

6) No history of psychiatric illness during the two years prior to the reported onset of the current episode of depression;

7) In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins or calcium supplements).

EXCLUSION CRITERIA:

The following conditions will constitute contraindications to treatment and will preclude a subject's participation in this protocol:

1) severe major depression with any of the following:

1. positive (threshold) response to SCID major depression section item # 9, suicidal ideation;
2. anyone requiring immediate treatment after clinical assessment;
3. severity ratings greater than moderate on the SCID IV interview (including postpartum psychosis);

2) current treatment with antidepressant medications

3) history of psychiatric illness during the two years before the reported onset of the current episode of depression or a history of either mania (DSM-IV criteria) or postpartum psychosis at any time in the past.

4) history of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers (greater than 10 cigarettes per day), varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease.

5) renal disease, asthma

6) hepatic dysfunction

7) women with a history of carcinoma of the breast, or 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

8) women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding

9) patients with a known hypersensitivity of estradiol, Alora, or medroxyprogesterone acetate

10) pregnant women

11) porphyria

12) diabetes mellitus

13) cholecystitis or pancreatitis

14) history of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia

15) recurrent migraine headaches

16) malignant melanoma

17) history of familial hyperlipoproteinemia