Effects of perimenopausal transdermal estradiol on self-reported sleep, independent of its effect on vasomotor symptom bother and depressive symptoms

Abstract

Objective: The aim of this study was to determine the efficacy of transdermal estradiol (E2) plus intermittent progesterone (EPT) for improving self-reported sleep in perimenopausal women, after controlling for vasomotor symptoms (VMS) bother and depressive symptoms.

Methods: Using a double-blind, placebo-controlled design, 172 healthy women meeting STRAW+10 criteria for being in the menopausal transition or early postmenopause were randomized to 12 months of transdermal E2 (0.1 mg/d) + 200 mg progesterone (12 d every 3 mo) or placebo. Using standard questionnaires, self-reported sleep, depression, and VMS bother were obtained at baseline and bimonthly postrandomization.

Results: Controlling for baseline levels, EPT (vs placebo) led to reductions in minutes to fall asleep (estimate = -0.12, P = 0.002) and number of awakenings (estimate = -0.24, P = 0.04) over the 12 months. Controlling for changes in VMS bother and depressive symptoms, EPT still predicted reductions in minutes to fall asleep (estimate = -0.28, P = 0.02) and number of awakenings (estimate = -0.11, P = 0.02) over the 12 months.

Conclusions: We extend existing research by demonstrating that hormone therapy (HT) in subjective sleep cannot be fully explained by improvements in VMS bother or depressive symptoms. Research to examine the mechanism (s) underlying HT's effects on sleep would have public health significance for perimenopausal women and also advance our general understanding of the pathophysiology of impaired sleep.