Estradiol variability, stressful life events, and the emergence of depressive symptomatology during the menopausal transition.

Objective: The aim of the study was to examine the role of estradiol fluctuation in triggering depressive symptoms in the menopausal transition and assess the role of recent very stressful life events (VSLEs) as a moderating factor in this relationship.

Methods: A total of 52 euthymic women in the menopausal transition or early postmenopause (age 45-60) who were assigned to the placebo arm of a randomized controlled trial of hormone therapy provided the data for this report. At enrollment, women's experience of recent VSLEs, depressive symptoms, serum estradiol, and progesterone were assessed. At months 1, 8, and 14, depressive symptoms and hormones were reassessed, and participants underwent a stressor battery involving a speech and a mental arithmetic task. Participants rated their feelings of anxiety, fear, anger, and rejection. The standard deviation of estradiol provided an index of hormone variability over the entire 14 months.

Results: Greater estradiol variability across the 14 months predicted greater depressive symptoms at month 14, though only in women reporting a higher number of VSLEs at baseline (39% of women reported ≤1 recent event). Greater estradiol variability also predicted greater feelings of rejection to the laboratory stressor at months 8 and 14. Furthermore, among women reporting higher VSLEs at baseline, feelings of rejection in response to the laboratory stressor at month 8 predicted depressive symptoms at month 14.

Conclusions: These data suggest that estradiol variability may enhance emotional sensitivity to psychosocial stress, particularly sensitivity to social rejection. Combined with VSLEs proximate to the menopausal transition, this increased sensitivity may contribute to the development of depressed mood.