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Sleep Disturbance Associated With Weight Gain During Menopause


Sleep quality may be as significant as estrogen withdrawal in determining weight gain risk in women, according to a study presented virtually at the Endocrine Society’s 2021 Annual Meeting.

In assessing weight gain during menopause, sleep disturbance may play an equally significant role to that of estrogen withdrawal, according to a study presented virtually at ENDO 2021, the Endocrine Society’s annual meeting.

Although hormonal changes during menopause are often thought to be the cause of weight gain, the Mayo Clinic says that it is instead a combination of several factors, including aging, lifestyle, and genetics. As another common symptom during menopause, sleep disturbance has independently been associated with weight gain in women.

“Possible mechanisms contributing to this weight gain may be changes in resting energy expenditure (REE) and/or nutrient utilization,” hypothesized the study authors.

Aiming to further examine the role of sleep fragmentation and pharmacologic estradiol (E2) withdrawal on REE and nutrient utilization, researchers recruited 21 healthy pre-menopausal women to participate in a 5-night inpatient study that used an experimental model to simulate sleep disturbance.

During the study, participants had 2 nights of uninterrupted sleep [8 hours (h) total time in bed (TIB)] followed by 3 nights of interrupted sleep (9-h TIB), in which they were woken by an alarm every 15 minutes for a sustained wake time of 2 minutes.

They then simulated E2 withdrawal through administering leuprolide, a drug that temporarily suppresses estrogen to levels similar to menopause, to a subset of 9 patients involved in the same sleep interruption protocol.

“Study diets consisted of 3 meals and a snack each day and were iso-caloric across the 2 visits. REE and nutrient utilization were assessed in the fasted state via indirect calorimetry and compared between E2 states following non-fragmented and fragmented sleep using linear mixed models,” explained study authors.

Compared with a normal night of sleep, 3 nights of disturbed sleep in participants was shown to alter fasting nutrient utilization, as shown by increases in the respiratory quotient (RQ; +3%; P = .03) and carbohydrate oxidation (+20%; P = .02), as well as a decrease in fat oxidation (-16%; P = .03).

This effect was similarly found in those administered leuprolide, even during non-fragmented sleep, in which increases in RQ (+5%; P = .01) and carbohydrate oxidation (+33%; P = .01), and a decrease in fat oxidation (-26%; P = .01) was reported.

"Our findings suggest that not only estrogen withdrawal but also sleep disturbances during menopause may contribute to changes in a woman's body that could predispose midlife women to weight gain," said lead researcher Leilah Grant, PhD, of Brigham and Women's Hospital, in a statement. "Helping women sleep better during menopause may therefore reduce the chances a woman will gain weight, which in turn will lower her risk of diabetes and other related diseases."

Although nutrient utilization was influenced, no effect of sleep fragmentation or E2 state was reported for REE. Additionally, there was no additive effect of sleep fragmentation on nutrient utilization in those with suppressed estrogen levels, which researchers suggest may indicate a possible ceiling (RQ and carbohydrate oxidation) and floor (fat oxidation) effect.


Grant LK, Coborn JE, Cohn A, et al. Effect of experimentally induced sleep fragmentation and hypoestrogenism on fasting nutrient utilization in pre-menopausal women. Presented virtually at: ENDO 2021; March 20-23, 2021. Abstract OR17-4.

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