Hormone sensitivity and stressful life events predict the effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial

Abstract

Internalizing mood symptoms are highly prevalent during the menopause transition (perimenopause). Prior research demonstrates that perimenopausal women with greater estradiol (E2) variability are more likely to experience depression symptoms, especially following recent stressful life events (SLEs). Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent SLEs. This research extends prior work by examining the relation between E2 and precise behavioral indicators of depression, including reward-seeking behaviors. The current study utilizes a randomized, double blind, placebo-controlled design to investigate whether sensitivity to E2 flux predicts the effects of a TE2 intervention on reward-seeking behaviors in perimenopausal women, and whether SLE’s moderate any observed associations. Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations, anxiety symptoms, and anhedonia levels. Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). There were no differences in EEfRT performance between randomized groups at baseline. Greater hormone sensitivity predicted more reward-seeking behaviors on the EEfRT task post-randomization, but only for participants randomized to TE2. Notably, the strength of this association increased when women experienced more SLEs. Perimenopausal women who are hormone sensitive with recent life stress may experience a greater benefit of TE2.