In patients with OSA, 12 weeks of PAP therapy increased morning intracellular NADPH levels in men but not women (0.7 vs -0.063, p=0.012), indicating sex differences in antioxidant capacity improvement.
Observational (n=25)
Does PAP therapy differentially improve intracellular oxidative stress biomarkers in men compared to postmenopausal women with obstructive sleep apnea?
PAP therapy for obstructive sleep apnea improves glutathione-based antioxidant capacity in both sexes, but men show a greater improvement in NADPH levels compared to postmenopausal women.
Absolute Event Rate: 0.7% vs -0.063%
p-value: p=0.012
Abstract Background Obstructive sleep apnea (OSA) increases in women after menopause and approaches that of men. Additionally, cardiometabolic health is known to decline in menopause concomitant with the loss of antioxidant capacity secondary to the cessation of reproductive hormone production, i.e. estrogen. In particular, the endogenous glutathione (GS)-based antioxidant defense system is diminished in both OSA at an age that corresponds with menopause onset. Thus, the presence of OSA in postmenopausal women can potentially accelerate oxidative stress and further increase the risk for adverse health consequences. While there are known sex-based differences in the clinical presentation and polysomnographic findings of OSA in women and men, sex differences in oxidative stress burden at baseline and with response to OSA therapy has not been well studied. We aimed to assess differences in intracellular (within the red blood cell RBC) markers of GS-associated antioxidant capacity in postmenopausal women and age matched men. In particular, we looked at complimentary measures including reduced and oxidized glutathione (GSH and GSSG), total GS, and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) to characterize the dynamic GS flux occurring within the RBC. Methods Male and female patients aged 52-75 years with minimal, well-controlled comorbidities and a body mass index (BMI) 40 kg/m2, not currently treated for OSA, and with an apnea-hypopnea index (AHI) ≥ 15 events/hr by AASM recommended criteria were included. Menopausal state was verified by clinical history. Intracellular GS, GSH, GSSG glutathione, and NADPH were measured by ELISA immediately after sleep offset, both at baseline and following 12 weeks of PAP therapy. Results A total of 25 participants (16 women and 9 men) were included for the current analysis. OSA severity was moderate in both men and women, with an AHI of 25.8 versus 21.9 events/hr, respectively. Average adherence across all participants was 6.32 hour per night, with no significant differences between men and women. Total GS levels, primarily driven by GSSG levels, increased equally in men and women with 3 months of PAP therapy by ∼ 10 unit µm (p = 0.02). However, there were sex differences in intracellular levels of NADPH with men but not women demonstrating an increase in morning NADPH levels after 12 weeks of PAP therapy: 0.7 versus −0.063, p = 0.012. Conclusion In the setting of OSA, PAP therapy differentially improves the reduction, cycling and maintenance of GS-based antioxidant capacity more in men than women as determined by NADPH levels. This abstract is funded by: NIH
Mahmoudi et al. (2026) conducted an observational in Obstructive Sleep Apnea (n=25). PAP therapy vs. Men vs Women was evaluated on Change in morning intracellular NADPH levels (p=0.012). In patients with OSA, 12 weeks of PAP therapy increased morning intracellular NADPH levels in men but not women (0.7 vs -0.063, p=0.012), indicating sex differences in antioxidant capacity improvement.