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Leilah Grant, PhD








Sleep and Circadian Disorders


Leilah K. Grant, Aviva Cohn, Mathena Abramson, Julia A. Russell, Aleta Wiley, Jamie E. Coborn, Margo D. Nathan, Jessica Harder, Frank A.J.L. Scheer, Elizabeth B. Klerman, Ursula B. Kaiser, Shadab A. Rahman, Hadine Joffe

Principal Investigator

Hadine Joffe


Impaired daytime sleepiness and neurobehavioral performance in premenopausal women following experimental sleep fragmentation and hypoestrogenism mimicking menopause

Menopause is a reproductive transition unique to women and understanding the impact of menopause-related changes in behavior and physiology is an important area of women’s health research. In this abstract, we report the results of a study investigating the effects of a menopause model of sleep fragmentation and estradiol withdrawal on daytime sleepiness and neurobehavioral performance.


Sleep disruption increases daytime sleepiness and impairs neurobehavioral performance. Given the high prevalence of hot-flash related sleep disruption during the menopause, we examined the influence of experimentally induced sleep fragmentation on sleepiness and neurobehavioral performance in women in both an estrogenized and hypo-estrogenized state.



We studied 20 premenopausal women in two 5-night inpatient studies repeated in the mid-to-late follicular phase (estrogenized) and following leuprolide-induced hypoestrogenism. During each admission there were two nights of unfragmented sleep [8-h time in bed (TIB)] and three nights of fragmented sleep [9-h TIB]. Sleep was fragmented using an auditory stimulus that produced 1 hour of wake after sleep onset without reducing total sleep time. Daytime subjective sleepiness (Karolinska Sleepiness Scale) and neurobehavioral performance (Psychomotor Vigilance Task) were assessed every 2-3 hours on study days 2-5. The effects of sleep condition and estradiol state on sleepiness, reaction time (RT) and attentional failures (RT>500ms) were examined using Generalized Linear Mixed Models.



Women reported feeling sleepier, had slower RTs and more attentional failures following sleep fragmentation compared to unfragmented sleep (p<0.01 for all). Neurobehavioral performance, but not sleepiness, was similarly affected by estradiol state; compared to the estrogenized state, women had increased RTs (p<0.01) and attentional failures (p<0.001) when in the hypo-estrogenized state. Additionally, there was a trend (p=0.06) toward there being a differential effect of sleep fragmentation by E2 state on neurobehavioral performance, but not sleepiness, such that the increase in RT and attentional failures in response to sleep fragmentation was only observed in the estrogenized state.



Eight hours of total sleep time may not be sufficient to maintain subjective sleepiness and neurobehavioral performance levels when sleep is not consolidated. These findings have important implications for understanding the role of sleep and E2-modulated cognitive impairment during the menopause transition.

Research Context