A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women

Study Objectives The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. Methods In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 minutes of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n=27) or placebo (n=29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. Results Mean baseline ISI scores were 18.1 (95% CI, 16.8-19.4) and 18.3 (95% CI, 17.2-19.5) in the suvorexant and placebo groups, respectively (p=0.81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant [-8.1 (95% CI, -10.2 to -6.0)] compared to placebo [-5.6 (95% CI, -7.4 to -3.9), p=0.04]. Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p<0.01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparison. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. Conclusion These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia.

The Influence of Menopause and Cardiorespiratory Fitness on Lipoprotein Particles in Midlife Women

Lipoprotein particles may provide better information about cardiovascular risk than standard cholesterol measures for women. Whether lipoprotein subclasses change with menopausal stage is unclear. Given the high prevalence of low cardiorespiratory fitness in midlife women and benefit to cardiovascular risk, it is also important to understand the effect of fitness on lipoprotein profiles. Purpose: To evaluate the influence of menopausal status and fitness on lipoprotein particles in healthy midlife women. Methods: Lipoprotein particles were measured in high-(HIGH,n=25) and low-fit(LOW,n=13) perimenopausal and late postmenopausal women, and in HIGH premenopausal(n=10), perimenopausal(n=12), and late postmenopausal women(n=13). Results: There were larger low-density lipoprotein particles(LDL-P, 21.7±0.06vs.21.3±0.1nm, p=0.002), more large LDL-P(623.1±32.8vs.500.2±52.6nmol/L, p=0.045), and fewer small LDL-P(145.5±31.4vs. 311.5±44.7nmol/L, p=0.001) in HIGH vs. LOW. High-density lipoprotein particles(HDL-P) were larger(10.1±0.1vs.9.7±0.1nm, p=0.002) in HIGH, with more large(14.8±0.7vs.11.0±0.9μmol/L, p=0.002), medium(12.9±0.8vs. 8.4±0.9μmol/L, p=0.002), and fewer small HDL-P(10.2±1.1vs.15.4±1.6μmol/L, p=0.009) compared to LOW. HIGH postmenopausal women had more large LDL-P(662.9±47.5nmol/L) compared to premenopausal women(479.1±52.6nmol/L, p=0.035), and more HDL-P(40.2±1.1μmol/L) compared to premenopausal(34.9±1.5μmol/L, p=0.023) and perimenopausal women(35.4±1.3μmol/L, p=0.033). Conclusion: High fitness positively influences lipoprotein particles in healthy perimenopausal and late postmenopausal women. In healthy fit women, menopause may not have a large influence on lipoprotein particles. Novelty Bullets: • In highly-fit women, menopause may not have a negative influence on lipoprotein particle subclasses. • High fitness is associated with a less atherogenic lipoprotein profile in perimenopausal and late postmenopausal women.

Cohort Differences in Well-Being Among Midlife and Older Women: Role of Self-Perceptions of Aging

The current study examines how cohort differences across two age-matched groups of midlife and older women from the Health and Retirement Study are associated with well-being and self-perceptions of aging (SPA). Women aged 51–60 (n=2318) and 61–70 (n=1650) were selected from the 2008 and 2018 waves. No significant cohort differences were identified for life satisfaction (Diener, Emmons, Larsen & Griffin, 1985) or positive SPA (Lawton, 1975; Liang & Bollen, 1983). The 2008 cohort of midlife women reported significantly higher negative SPA compared to 2018 (p<.05). Linear regression analyses find that cohort and SPA are significantly associated with life satisfaction in both age groups, and that the association of negative SPA differs by cohort for the midlife women (p<.01). Implications are discussed within the life course developmental framework.