Naturally Occurring Changes in Estradiol Concentrations in the Menopause Transition Predict Morning Cortisol and Negative Mood in Perimenopausal Depression

Risk of depression increases considerably during the menopause transition (or perimenopause)—the 5 to 6 years surrounding the last menstrual period. Although the mechanisms underlying this increased risk are unknown, we have hypothesized that excessive estradiol (E2) fluctuation, which accompanies the perimenopause, may be implicated. We have furthermore proposed that dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis may underlie E2 fluctuation’s effect on mood. This study examined the relationship between weekly changes in salivary E2, salivary cortisol levels, and weekly mood in 30 perimenopausal women recruited to achieve equal numbers of women with current depression, past depression, and no history of depression. Greater weekly increases in E2 were associated with increased cortisol among past and currently depressed women; greater E2 increases were also associated with negative mood among currently depressed women. These findings provide evidence that HPA axis dysregulation, correlated with E2 fluctuation, may be implicated in the pathophysiology of perimenopausal depression.