Sleep Fragmentation and Estradiol Suppression Decrease Fat Oxidation in Premenopausal Women

Abstract

Context Body fat gain associated with menopause has been attributed to estradiol (E2) withdrawal. Hypoestrogenism is unlikely to be the only contributing factor, however. Objective Given the links between sleep and metabolic health, we examined the effects of an experimental menopausal model of sleep fragmentation on energy metabolism. Design Premenopausal women were studied in two 5-night inpatient studies during the mid-to-late follicular phase (estrogenized; n=20) and repeated in a subset (n=9) following leuprolide-induced E2 suppression (hypo-estrogenized). During each 5-night study, there were two nights of unfragmented sleep followed by three nights of fragmented sleep. Setting Academic medical center. Participants Twenty premenopausal women (age 21-45 years) Interventions Sleep fragmentation and estradiol suppression. Main outcome measures Indirect calorimetry was used to assess fasted resting energy expenditure (REE) and substrate oxidation. Results Sleep fragmentation in the estrogenized state increased the respiratory exchange ratio (RER) and carbohydrate oxidation while decreasing fat oxidation (all p<0.01). Similarly, in the hypo-estrogenized state without sleep fragmentation, RER and carbohydrate oxidation increased and fat oxidation decreased (all p<0.01); addition of sleep fragmentation to the hypo-estrogenized state did not produce further effects beyond that observed for either intervention alone (p<0.05). There were no effects of either sleep fragmentation or E2 state on REE. Conclusions Sleep fragmentation and hypoestrogenism each independently alter fasting substrate oxidation in a manner that may contribute to body fat gain. These findings are important for understanding mechanisms underlying propensity to body fat gain in women across the menopause transition.

Effect of sleep restriction on insulin sensitivity and energy metabolism in postmenopausal women: A randomized crossover trial

“…In the second arm of this study, a smaller subset of nine premenopausal women underwent monthly injection of the gonadotropin-releasing hormone agonist leuprolide acetate to induce menopause (hypo-estrogenized state), followed next by short-term sleep fragmentation to study its effect on energy metabolism. They observed that a hypo-estrogenized (postmenopausal) state reduced fat oxidation, but the addition of sleep fragmentation did not further alter fat oxidation [15]. Although our findings suggest that SR (rather than sleep fragmentation) reduces fat oxidation in postmenopausal women, this may be due in part to the fact that women in our study had previously undergone a natural menopause transition years prior rather than a more recent experimental menopause transition [15].…”

“…Our finding that four nights of SR reduced fat oxidation only during insulin infusion, and not under resting conditions, was contrary to our hypothesis. To our knowledge, only one experimental study has examined the effect of sleep disturbances during menopause on energy expenditure and substrate oxidation [15]. In one arm of this study, short‐term (three nights) sleep fragmentation was administered to 20 premenopausal women, resulting in decreased fat oxidation (by indirect calorimetry).…”

“…In this well‐controlled study, both normal sleep and sleep fragmentation were administered to premenopausal women as well as a subset of women undergoing experimental menopause (via administration of gonadotropin‐releasing hormone agonist leuprolide acetate) [15]. Compared with normal sleep, short‐term sleep fragmentation reduced fat oxidation (by indirect calorimetry) in premenopausal women; however, sleep fragmentation in the experimental menopause state (hypo‐estrogenized) did not further reduce fat oxidation [15]. To the best of our knowledge, no other studies have investigated how sleep disturbances (e.g., shortened and fragmented sleep, poor sleep quality) alter metabolism during perimenopause and into the postmenopausal years.…”

“…To date, only one experimental study has examined the within‐participant effect of sleep disturbances during menopause on energy metabolism [15]. In this well‐controlled study, both normal sleep and sleep fragmentation were administered to premenopausal women as well as a subset of women undergoing experimental menopause (via administration of gonadotropin‐releasing hormone agonist leuprolide acetate) [15].…”

“…To date, only one experimental study has examined the within‐participant effect of sleep disturbances during menopause on energy metabolism [15]. In this well‐controlled study, both normal sleep and sleep fragmentation were administered to premenopausal women as well as a subset of women undergoing experimental menopause (via administration of gonadotropin‐releasing hormone agonist leuprolide acetate) [15]. Compared with normal sleep, short‐term sleep fragmentation reduced fat oxidation (by indirect calorimetry) in premenopausal women; however, sleep fragmentation in the experimental menopause state (hypo‐estrogenized) did not further reduce fat oxidation [15].…”