The transition to menopause may stir hormones and bring on depression in women with no history of the mood disorder, according to two studies.

In an evaluation over eight years of 231 premenopausal women, ages 35 to 47, with no history of depression, high depression scores (16 or more) were almost four times more likely to occur during a woman’s menopausal transition compared with her premenopausal status (odds ratio, 4.29; 95% CI, 2.39-7.72, P<0.001), researchers reported in the April issue of the Archives of General Psychiatry.

Furthermore, depression scores, assessed by the Center for Epidemiological Studies of Depression scale (CES-D), were significantly linked to changes in hormonal status, according to Ellen Freeman, Ph.D., of the University of Pennsylvania here and colleagues.

Within individual women, the change in menopausal status brought about destabilizing hormonal effects, including increased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), decreased levels of inhibin B, and greater variability of estradiol, FSH levels, and LH.

The hormone-depression results held even after adjusting for other risk factors, such as smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status, the researchers reported.

On average, the women were 4.58 times more likely to have higher FSH levels (P=.001), three times likelier to have higher LH levels (P=.002), and 63% more likely to have lower inhibin B levels (P=.001) at the time of high CES-D scores compared with the time before the high scores, Dr. Freeman said.

The researchers also found that a clinical diagnosis of depressive disorder was 2.5 times more likely to occur during a woman’s menopausal transition compared with her premenopausal status (OR, 2.50, 95% CI, 1.25-5.02, P=0.01). Diagnoses were assessed by the Primary Care Evaluation of Mental Disorders (PRIME-MD).

The hormone measures were also significantly associated with a clinical diagnosis of depressive disorder, Dr. Freeman said. For example, on average, women with clinical depressive disorder were 9.33 times more likely to have higher FSH levels (P=.001) and 4.47 times more likely to have higher LH levels (P=.002) than before the diagnosis of depressive disorder, the researchers said.

“Transition to menopause and its changing hormonal milieu are strongly associated with both new onset of high depressive symptoms and new onset of diagnosed depressive disorders in women with no history of depression,” Dr. Freeman said. The results also indicated that other health and demographic factors, such as hot flashes, PMS, and smoking status, are also part of the multifactorial nature of depressive symptoms.

“Further follow-up study is needed to determine the extent to which the reports of depressed mood are limited to the perimenopausal period and to determine whether the identified risk factors are associated with more persistent depression,” she concluded.

In the same issue of the Archives of General Psychiatry, a six-year study of 460 women, ages 36 to 45, with no history of depression, also found that early transition to menopause may increase the risk of first-time depression.

Compared with 134 women who remained premenopausal, 326 women who entered menopausal transition earlier were twice as likely (adjusted OR 1.9 [95% CI 0.9-4.0]) to develop significant depressive symptoms, according to Lee Cohen, M.D., of Massachusetts General Hospital and colleagues of the Harvard Study of Moods and Cycle. This relationship, the researchers said, held even after adjustment for age at study enrollment and history of negative life events.

The increased risk for depression, was somewhat greater among women with self-reported vasomotor symptoms, they said, adding that the relationship between hot flashes and depression is not fully understood and may result from a number of factors such as sleep disruption. On the other hand, Dr. Cohen said, the relationship may be caused by changes in the reproductive hormone milieu to which a woman may be sensitive.

The study included women living in seven Boston-area communities. New onset of depression was based on structured clinical interviews, CES-D scores, and self-administered questionnaires. The women were interviewed every six months through the initial three years of follow-up and then at substantially greater intervals, the later larger intervals being a limitation of the study, the researchers said.

However, they added, when they limited analysis to the first three years of follow-up, they still observed that 7.2% of the women who made the perimenopausal transition developed new onset of depression, compared with 2.9% of those who remained premenopausal (OR 2.7. 95% CI, 1.0-6.9, P= .04).

A spectrum of symptoms and syndromes - severe vasomotor symptoms, loss of bone density, sexual dysfunction, decline in cognitive function - has been extensively described during the menopausal transition, the authors wrote. “Thus, the comorbidity of these problems with perimenopause-associated depression could affect many aging women, leading to a compounded burden of illness,” they concluded.

Primary source: Archives of General Psychiatry, 2006; 63:375-382