SAT-127 Impact of Sleep Interruption on Circulating Oxytocin Levels and Mood Disturbance in Women Under High and Low Estradiol Conditions

Abstract Disclosure: I. Gonsalvez: None. E.A. Lawson: Up To Date, Thermo Fisher Scientific, Danaher Co, Tonix Pharmaceuticals, Merck, West Pharmaceutical Services, Zoetis, Intuitive Surgical. L.K. Grant: None. J.A. Harder: None. M.D. Nathan: None. D. Fida: None. H.C. Kim: None. A. Wiley: None. H. Joffe: Merck, Bayer, Inc., NIH. S.A. Rahman: None. Background: Oxytocin is a hypothalamic neuropeptide hormone and neuromodulator involved in reproductive physiology, social behavior and the stress response, with oxytocin levels increasing after a stressor to attenuate HPA axis activity. Animal models and some human data show that oxytocin has an antidepressant/anxiolytic effect. As women undergo physiological changes during reproductive transitions (increases in oxytocin in late pregnancy; decreases in acute postpartum and menopausal transition), women’s susceptibility to sleep and mood disorders increases. These concurrent changes point to a potential impact of oxytocin on the health and mood of women during these transitions. However, few studies have examined the role of oxytocin in reproductive-associated mood disorders in women. In an experimental model mimicking menopausal and postpartum transitions, we examine the impact of sleep interruption and estradiol suppression on circulating oxytocin levels and mood. Methods: Healthy premenopausal women completed two 5-night inpatient studies (2 nights of uninterrupted sleep followed by 3 nights of experimentally induced sleep interruption, with similar sleep duration in both conditions), once in the mid-to-late follicular phase (n=38) and again after gonadotropin-releasing hormone agonist-induced estradiol suppression (subset, n=27). Serum oxytocin was measured by LCMS and mood disturbance was evaluated using the Profile-of-Mood-States (POMS, higher scores worse mood). In both estradiol states, mood assessments were performed in the morning and serum samples for oxytocin were collected in the evening. Results: Oxytocin levels and mood disturbance significantly increased after sleep interruption across estradiol states ([mean±SE] 28.7±2.1 pg/mL vs. 36.4±2.2 pg/mL, p=0.002; 5.5±2.4 vs. 12.3±2.4, p<0.0001- respectively). Following estradiol suppression, oxytocin levels and mood disturbance did not change significantly (p≥0.15). Higher oxytocin levels correlated with more mood disturbance (Cohen’s d=0.49, p=0.024). Conclusion: Mirroring the acute postpartum phase and menopausal transitions, both oxytocin levels and mood disturbance increased acutely in healthy women following exposure to the characteristic sleep interruption pattern of these reproductive transitions. Our results also show a positive association between oxytocin levels and worsening in mood. This may suggest a counteracting effect where oxytocin levels increase in response to worsened mood, but mechanistic studies are required to study the direction and causality of this association. Presentation: Saturday, July 12, 2025