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Am Fam Physician. 2006;74(7):1198-1200

There is little information about the impact of the transition from premenopause to perimenopause on mood disorders. Some studies have concluded that mood disorder symptoms are not associated with natural menopause but result from stress, relationship problems, other menopausal symptoms, or previous depression. Other more recent studies have discovered an increase in depressive symptoms in perimenopausal women compared with premenopausal women. In one longitudinal study, women in perimeno-pause were at a significantly greater risk of clinical depression than those in the premenopause period. This increased risk for depressive symptoms may be related to the change in the reproductive hormones during the transition phase. However, this theory has not been tested. Freeman and associates conducted a population-based study to determine if new onset of depressive symptoms in menopause transition correlated with menopausal status, reproductive hormones, and other risk factors.

Participants included women 35 to 47 years of age who were randomly selected from one county in Pennsylvania and who did not have depression based on the results from two scales. They were included in the study if they had three normal menstrual cycles in the previous months, an intact uterus, and at least one ovary. Women were excluded if they currently were using psychotropic or hormone medications, were pregnant or breastfeeding, had serious health problems that could compromise ovarian function, or reported alcohol or drug abuse within the preceding year. Data were collected on the women for 10 assessment periods from 1996 to 2004: the first at baseline, then every eight months (for assessment periods two through seven), and then annually for a total of eight years. Menopausal status and symptoms were evaluated at each visit and classified into two stages defined as premenopause and transition. In addition, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured at multiple times during the study. The main outcome was measured using the Centers for Epidemiological Studies of Depression scale (CES-D) and the Primary Care Evaluation of Mental Disorders (PRIME-MD). Information about other risk factors for depression also was gathered during the study.

At the end of the study, 116 of the 231 participants who had no history of depression at baseline reported high scores on the CES-D scale, suggesting the presence of depression. Twenty-six percent of the women were diagnosed with depressive disorder based on the other testing scores. Those women who were in the transition phase of menopause were more than four times more likely to have high CES-D scores and more than twice as likely to have a depressive disorder than those who were premenopausal. Increased levels of FSH and LH and fluctuating levels of FSH, LH, and estradiol were significantly associated with high CES-D scores. In addition, hormone levels significantly correlated with the diagnosis of depression.

The authors conclude that the transition to menopause and the associated changes in hormone levels are strongly correlated with new onset of depression among women with no history of depression. They add that further studies are needed to determine if this depression persists beyond the perimenopause period.

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