SAT-051 Prolonged intranasal oxytocin treatment effects on reproductive hormones in adults with obesity

Abstract Disclosure: F. Galbiati: None. S. Hiranandani: None. M. Wronski: None. F. Plessow: Inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder).. K. Holman: None. E. Asanza: None. S.E. Smith: None. M. Muhammed: None. E. Golden: None. N. Hadaway: None. E. Getachew: None. A. Aulinas: None. E.A. Lawson: Up To Date, Inventor on US provisional patent application no. 63/467,980 (Oxytocin-based therapeutics to improve cognitive control in individuals with attention deficit hyperactivity disorder)., Elizabeth A. Lawson and/or immediate family member holds stock in Thermo Fisher Scientific, Zoetis, Danaher Corporation, Intuitive Surgical, Merck, and West Pharmaceutical Services, Grant support and research study drug from Tonix Pharmaceuticals. Objective: Oxytocin (OXT) is a posterior pituitary hormone best known for its role in parturition and lactation also implicated in many physiologic functions, and intranasal (IN) OXT is under investigation as a therapeutic for several conditions, including obesity. Interplay between anterior and posterior pituitary is not well understood and given the established role of OXT in reproduction, it is important to examine IN OXT effects on prolactin (PRL) and the hypothalamic-pituitary-gonadal (HPG) axis. In lactating women and non-lactating animals, OXT increases PRL. Animal studies showed a positive feedback loop between OXT and estradiol in females. In male rats, OXT induced spermatogenesis and mediated favorable effects of testosterone (T) on metabolism, and a single dose of IN OXT increased salivary T in healthy men. There are no data on prolonged OXT treatment effects on PRL or the HPG axis in humans. To better elucidate physiology and increase our understanding of reproductive safety of prolonged IN OXT, we leveraged our completed randomized controlled trial of 8-weeks IN OXT in adults with obesity to investigate effects on circulating PRL and sex steroid levels. We hypothesized that IN OXT would increase circulating PRL, total/free T (men), estradiol (women); and would not alter menstrual cycle length (women). Methods: 61 adults with obesity [52% women, not on oral contraceptives; age (mean±SEM) 33.2±0.9 years; body mass index (BMI) 37.9±0.8] were randomized (1:1) to receive 8-weeks IN OXT (24 IU) or placebo four times daily. Fasting blood was drawn pre-treatment and at week 6 for PRL and weeks 4 and 8 for sex hormones. Participants’ clinical characteristics and on-treatment menstrual cycle length were analyzed with t-tests (normally) or Wilcoxon tests (non-normally distributed variables). A linear mixed effects model with the factors Treatment, Time (categorical) and the Treatment*Time interaction term was used to analyze PRL and sex steroid levels. Results: Pre-treatment age, BMI, sex distribution, PRL (OXT: 7.9±0.8; placebo: 8.1±0.8 ng/mL), estradiol (OXT: 114.8±22.7; placebo: 127.0±23.4 pg/mL), total T (OXT: 436.7±44.6; placebo: 434.3±47.9 ng/dL), and free T (OXT: 4.1±0.2; placebo: 4.5±0.2 ng/dL) levels did not differ across treatment groups (p’s≥0.24). OXT vs. placebo did not affect PRL or sex steroid levels over time (Treatment*Time p’s≥0.19). On-treatment mean menstrual cycle length did not differ across groups (OXT: 27.0±1.1; placebo: 30.2±1.9 days; p=0.16). Conclusion: In this study, 8-weeks IN OXT did not alter PRL or sex steroid levels, possibly due to cross-species differences in OXT functioning, acute vs. chronic IN OXT effects, or obesity-related PRL/HPG axes resistance to OXT. OXT had no effects on menstrual cycle length. These data provide support for reproductive safety of OXT-based therapeutics in adults with obesity. Presentation: Saturday, July 12, 2025