Perimenopause May Trigger First-Time Depression

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.