Effect of sleep interruption and leuprolide-induced hypoestrogenism on fasting nutrient utilization in pre-menopausal women

Leilah Grant, PhD
Department of Medicine
Division of Sleep and Circadian Disorders
Poster Overview

Both sleep disturbances and menopause can lead to weight gain in women and this may be caused by changes in the body’s use of nutrients, such as fats. In this study we examined the effects of sleep interruption and estrogen suppression (temporarily caused by a drug) on nutrient utilization in 21 women. A 5-night laboratory study that included two nights of normal, uninterrupted sleep, and three nights of interrupted sleep with frequent awakenings mimicking menopausal sleep disruption was repeated in both a high- and low-estrogen state. After normal and interrupted sleep, we measured oxygen consumption and carbon dioxide production to detect what nutrient source the body was using. We found that sleep interruption when estrogen was high led to reduced use of fats for energy. The same reduction in fat use was also seen when estrogen was suppressed, but this low estrogen effect was not made worse by simultaneous sleep interruption. Overall, our results suggest sleep disturbance and estrogen suppression both lead to changes in the body’s use of nutrients, which may contribute to weight gain. This is important for understanding weight gain during menopause where estrogen is low and sleep problems are common.

Scientific Abstract

Background: Sleep disturbances and estradiol (E2) withdrawal during menopause are associated with weight gain in women. A possible mechanism contributing to this weight gain may be changes in nutrient utilization.


Design: We studied 21 pre-menopausal women during 5-night inpatient studies repeated in the mid-to-late follicular phase (high-E2) and following leuprolide-induced hypoestrogenism (low- E2). During each admission there were two nights of uninterrupted sleep and three nights of fragmented sleep. Study diets were iso-caloric. Fasting substrate utilization was assessed via indirect calorimetry and compared between E2 states following uninterrupted and fragmented sleep using linear mixed models.


Results: Sleep fragmentation in the high-E2 state increased the respiratory quotient (RQ; +3%; p=0.03) with an accompanying increase in carbohydrate oxidation (+20%; p=0.02) and decrease in fat oxidation (-16%; p=0.03). The same effect was observed in response to E2- suppression during uninterrupted sleep [increased RQ (+5%; p=0.01) and carbohydrate oxidation (+33%; p=0.01) and decreased fat oxidation (-26%; p=0.01)]. There was no additive effect of sleep fragmentation on substrate utilization in the low-E2 state suggesting a possible ceiling and floor effect.


Conclusion: Sleep fragmentation and hypoestrogenism influenced fasting nutrient utilization in a way that may contribute to weight gain associated with sleep disturbance and E2 withdrawal during menopause.

Clinical Implications
Menopause is characterized by estrogen withdrawal and often accompanied by sleep interruption. Both sleep interruption and hypoestrogenism were shown to alter fasting nutrient utilization in a manner that may contribute to weight gain in menopausal women.
Research Areas
Leilah K. Grant, Jamie E. Coborn, Aviva Cohn, Mathena Abramson, Julia A. Russell, Aleta Wiley, Margo D. Nathan, Frank A.J.L. Scheer, Elizabeth B. Klerman, Ursula B. Kaiser, Shadab A. Rahman*, Hadine Joffe*
Principal Investigator
Hadine Joffe

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