FRI411 Pharmacologically Induced Hypoestrogenism And Experimentally Induced Menopause-Pattern Sleep Fragmentation Independently Influence Circulating Lipids, Heart Rate, And Blood Pressure In Women
Authors: Grant Leilah K , Cohn Aviva , Crawford Sybil , Harder Jessica , Nathan Margo D , Gonsalvez Irene , Luo Tianyu , Menezes Ellexa , Roy Ancella , Wiley Aleta , Scheer Frank A J L , Klerman Elizabeth , Kaiser Ursula B , Mora Samia , Andrew Taylor J , Joffe Hadine , Rahman Shadab A 
Published: October 2023

Abstract
Disclosure: L.K. Grant: Grant Recipient; Self; Brigham and Women’s Hospital, Women’s Health Access Matters. A. Cohn: None. S. Crawford: None. J. Harder: Consulting Fee; Self; Altman Health, O’Rouke & Hawk, LLP. Grant Recipient; Self; Brigham and Women’s Hospital, President and Fellows of Harvard College. Owner/Co-Owner; Self; Jessica Harder, MD. Stock Owner; Self; Altman Health. Other; Self; Centerfield Media Holding Company. M.D. Nathan: None. I. Gonsalvez: None. T. Luo: None. E. Menezes: None. A. Roy: None. A. Wiley: None. F.A. Scheer: Consulting Fee; Self; University of Alabama. Other; Self; Board of Directors for the Sleep Research Society. E. Klerman: Consulting Fee; Self; American Academy of Sleep Medicine Foundation, Sleep Research Society Foundation, Circadian Therapeutics, National Sleep Foundation, Yale University Press. U.B. Kaiser: None. S. Mora: Consulting Fee; Self; Pfizer, Inc. J. Taylor: None. H. Joffe: Consulting Fee; Self; Bayer, Inc., Hello Therapeutics. Grant Recipient; Self; Merck, Pfizer, Inc., NIH. S.A. Rahman: Consulting Fee; Self; Sultan & Knight Limited, Bambu Vault LLC, Lucidity Lighting Inc. Grant Recipient; Self; Seoul Semiconductor Co. Ltd, Biological Innovation and Optimization Systems, LLC, Pfizer, Inc., Merck & Co., Lighting Science Group. Speaker; Self; Starry Skies Lake Superior, University of Minnesota Medical School, PennWell Corp, Seoul Semiconductor Co. Ltd. Stock Owner; Self; Melcort Inc.
Introduction: The risk of cardiovascular disease (CVD) in women increases at menopause. Although declining levels of estradiol (E2) have been implicated in the increase in CVD risk for midlife women, it remains difficult to isolate these effects from the parallel changes in chronological age, and other potential contributing, mediating and modifying factors such as menopause-pattern sleep fragmentation (increased awakenings but no change in overall sleep duration). Here, we investigated whether hypo-estrogenism (hypo-E2) and sleep fragmentation increase CVD risk factors [lipids, blood pressure (BP)] in an experimental menopause model implemented in premenopausal women. Method: Two 5-night inpatient studies performed in the mid-to-late follicular phase (E2 = 48.7±29.5 pg/mL) and repeated following leuprolide-induced hypo-E2 (E2 = 7.5±5.9 pg/mL) were completed in 27 premenopausal women (mean age = 28.4±5.6 years). Each admission involved 2 nights of unfragmented sleep [8-h time-in-bed (TIB)] followed by 3 nights of sleep fragmentation, induced by auditory stimuli distributed across the night, producing 1-hr of cumulative wakefulness while enabling equal sleep opportunity (9-h TIB). BP and heart rate (HR) measurements were collected within 1 hour of wake in a semi-supine position each morning; fasting serum lipids were collected during unfragmented sleep and again after 3 nights of sleep fragmentation, during both inpatient stays. The effect of sleep fragmentation, E2 state and their interaction were assessed using generalized linear models to account for repeated measures. Results: Relative to the estrogenized state, the hypo-E2 state had a significant increase in total cholesterol (156±5 vs. 167±6 mg/dL, p&lt;.001), triglycerides (72±5 vs 79±7 mg/dL, p&lt;.001), HDL-C (58±3 vs. 62±3 mg/dL, p&lt;.01), LDL-C (81±4 vs. 86±5 mg/dL, p&lt;.05) and mean arterial pressure (MAP; 79±1 vs. 81±1 mmHg, p&lt;.05) and a trend toward increased diastolic BP (63±1 vs. 65±1 mmHg, p=.07), with a significant compensatory decrease in HR (67±2 vs. 65±2 bpm, p&lt;.001). Compared to the unfragmented sleep condition, sleep fragmentation resulted in a significant increase in HR (64±2 vs. 68±2 bpm, p&lt;.001) and a trend toward increased systolic BP (109±1 vs. 110±1 mmHg, p=.08). There was no effect of sleep fragmentation on lipid levels, diastolic BP, or MAP, and no interaction between sleep fragmentation and E2 for any of the variables. Conclusion: These experimental findings show that pharmacologically induced hypo-E2, but not sleep fragmentation, increase circulating lipids levels in pre-menopausal women. Additionally, pharmacological E2-suppression increased BP and decreased HR, whereas sleep fragmentation increased both BP and HR. Together, these findings suggest that both E2 decline, and sleep fragmentation may uniquely contribute to the increase in CVD risk during the menopause transition.
Presentation: Friday, June 16, 2023