The purpose of this study is to investigate mood and behavior changes in the time period surrounding and including menopause. This is an observational study; volunteers who participate will not receive any new or experimental therapies.

Controversy exists regarding the relationship between estrogen and progesterone (gonadal steroid) changes and midlife-onset depression. This study will examine the role of gonadal steroids in perimenopausal mood and behavioral disorders.

Perimenopausal women with depression symptoms and a control group of healthy perimenopausal volunteers will be compared to identify correlates of the occurrence of depression. Participants with depressive symptoms may also participate in companion studies that will test the antidepressant efficacy of phytoestrogens and selective estrogen receptor modulators (SERMS).

A group of younger pre-perimenopausal women with normal menstrual cycle functioning will be followed through menopause in an effort to confirm the association of depression onset with changes in reproductive endocrine functioning....

Controversy exists regarding the relevance of changes in gonadal steroids for midlife onset depressions. In this protocol, we examine the possible role of gonadal steroids in these disorders in two ways. First, we identify groups of both depressed and asymptomatic women who are in the perimenopause (as defined endocrinologically). Patients and controls are compared using baseline biological and phenomenological (e.g. life events, hot flushes) measures in an attempt to identify potentially meaningful correlates of the occurrence of depression. Patient subjects also serve as participants in companion protocols designed to identify the antidepressant efficacy of estradiol and DHEA administration. Second, we identify younger preperimenopausal women with normal menstrual cycle function, who are followed longitudinally through the menopause in an effort to confirm the association of depression onset with change in reproductive endocrine function. This protocol, then, serves as a screening protocol to recruit subjects who are characterized with standard measures in this protocol and then offered participation in related studies.

• PATIENT/VOLUNTEER ENROLLMENT

CROSS-SECTIONAL SCREENING:

INCLUSION CRITERIA

History within the last one year of at least one month with perimenopause-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of functional impairment;

Age 40-60;

History of the onset of menstrual irregularity during the past six months but not greater than one year of amenorrhea (i.e., not postmenopausal);

Biological evidence of a deterioration of normal ovarian activity, specifically, plasma FSH levels persistently elevated (greater than 14 IU/L) drawn at two week intervals over a period of eight weeks;

No prior estrogen replacement therapy for treatment of perimenopausal physical or emotional symptoms within the last six months.

Good medical health

CONTROL GROUP

A control group of age-matched perimenopausal women who meet patient selection criteria with the exception of the presence of mood or behavioral disorders will also be sought.

LONGITUDINAL SCREENING:

The pre-perimenopausal women (regular cycling) will be women who meet the following criteria:

Regular menstrual cycle function (21-34 days),

Absence of current mood or behavioral disturbances as determined by a structured diagnostic interview,

Plasma gonadotropin levels in pre-perimenopausal range (less than 14 IU/L),

In good medical health,

Medication free.