Cardiovascular Endocrinology

SUN-229 - Cardiometabolism and Insomnia Symptoms: Effect of the Orexin Receptor Antagonist Suvorexant in Midlife Women with Comorbid Insomnia and Metabolic Syndrome Indicators

Sunday, June 14, 2026

9:00 AM - 4:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

CS

Clara O. Sailer, MD, PhD

Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA
Brookline, Massachusetts, United States

Co-Author(s)

SR

Shadab Rahman, PhD

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
AC

Aviva Cohn, MD

Department of Endocrinology, Rutgers Robert Wood Johnson Medical School, Rutgers, NJ, USA
New Brunswick, New Jersey, United States
HK

Hannah C. Kim, MS

Brigham and Women's Hospital
Boston, Massachusetts, United States
LH

Liane Hunter, MD

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
IG

Irene Gonsalvez, MD

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
JH

Jessica Harder, MD

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
NF

Natalie Feldman, MD

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
LG

Leilah Grant, MD

Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Boston, United States
SC

Sybil Crawford, PhD

University of Massachusetts Medical School, Graduate School of Nursing, Worcester, MA, USA;
Worcester, Massachusetts, United States
AP

Ananya Pani, MPH

Mary Horrigan Connors Center for Women's Health Research, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA
Boston, Massachusetts, United States
AW

Aleta Wiley, MPH

Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Boston, Massachusetts, United States

Senior Author/Primary Investigator(s)

HJ

Hadine Joffe, MD, MSc

Brigham and Women's Hospital, Dana Farber Cancer Institute, & Harvard Medical School, United States

Background: Unfavorable cardiometabolic changes, such as elevated blood glucose, dyslipidemia, and hypertension, have been associated with the menopausal transition, especially in women who experience vasomotor symptoms (VMS). Nighttime VMS precipitate sleep fragmentation, which further worsens cardiometabolic health. Dual orexin receptor antagonists (DORAs) reduce VMS-related sleep fragmentation in midlife women, whether sleep improvement also improves cardiometabolic biomarkers remains unknown.

Methods: We conducted a randomized, double-blind, placebo-controlled, crossover trial involving four-week treatment blocks using the DORA suvorexant (20mg nightly) in late peri-/early postmenopausal women. Eligible women had insomnia disorder, nighttime VMS, >30 minutes of wake after sleep onset (WASO), and at least one metabolic syndrome component (e.g., prediabetes, hypertension, dyslipidemia), but not sleep apnea. The primary endpoint was insomnia severity index (ISI). Secondary endpoints were diary-reported WASO, fasting blood glucose, and lipid profile. Outcome measures were within-person change for each endpoint over the 4-week treatment block using linear mixed-model regression analysis, and correlations between changes in sleep measures and cardiometabolic biomarkers.

Results: For the 29 women in this trial (mean ± SD age = 54.4 ± 4.7 years; BMI 26.9 ± 4.3 kg/m2), baseline values showed clinically significant insomnia and sleep fragmentation (mean ± SD: ISI 15.9 ± 3.6; WASO 50.9 ± 20.3 minutes); 89.7% (N = 26) had dyslipidemia, 31% (N = 9) had prediabetes, and 20.7% (N = 6) had hypertension. Suvorexant, as compared to placebo, led to a significantly greater reduction in ISI scores (-5.8 ± 4.9 vs. -2.7 ± 6.2, p = 0.038) and a greater numeric but not statistical reduction in WASO (-16.8 ± 20.4 vs. -5.8 ± 22.3 minutes, p = 0.14). There were no differences (all p > 0.32) between suvorexant and placebo in the effect on fasting blood glucose (2.1 ± 1.6 vs. -0.1 ± 1.6 mg/dl), LDL-cholesterol (5.9 ± 17.5 vs. 2.8 ± 21.0 mg/dl), HDL-cholesterol (-1.7 ± 7.4 vs. -1.8 ± 7.7 mg/dl), or triglycerides (-2.7 ± 26.1 vs. -4.0 ± 39.9 mg/dl). Change in ISI and WASO did not correlate with fasting glucose, HDL, LDL, or triglycerides (all p > 0.1).

Conclusion: Using a robust cross-over trial design, our results show that, relative to placebo, suvorexant treatment significantly improves insomnia severity and numerically attenuates sleep fragmentation in midlife women with VMS-associated insomnia in the context of mild comorbid metabolic disruption. However, despite these beneficial effects on sleep, cardiometabolic biomarkers did not improve with short-term treatment. These findings raise the possibility that suvorexant’s effective treatment of VMS-associated insomnia does not improve comorbid adverse cardiometabolic biomarkers in this population with a mixed cardiometabolic health background.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*