Oxytocin-induced changes in free T3/free T4 ratio and relationship with quality of life in adults with obesity

Abstract Context Oxytocin (OXT) is an anorexigenic, anxiolytic, and antidepressant neurohormone under investigation for obesity treatment. Mechanisms underlying OXT psychological effects are not fully understood, and human data on OXT modulation of the thyroid axis are lacking. Our 8-week trial of intranasal OXT in adults with obesity showed improved mental health–related quality of life (MHQoL) measured by the Short-Form 36 Health Survey vs placebo. Increased T4 and decreased T3 have been linked to depression. The free (bioactive) T3 (fT3)/free T4 (fT4) ratio, a marker of thyroid function in euthyroid patients, is associated with improved mental health. Objective To determine whether 6 weeks of intranasal OXT vs placebo modulates (1) the thyroid axis and (2) the relationship between fT3/fT4 and MHQoL changes. Design Eight-week randomized clinical trial, secondary analysis. Setting Tertiary academic center. Participants Sixty-one adults with obesity. Interventions Eight weeks of intranasal OXT (24 IU) 4× daily or placebo. Main outcome measures Pre- and posttreatment fasting thyroid hormones (week 6) and MHQoL (week 8). Results Six weeks of intranasal OXT vs placebo impacted fT3/fT4 (treatment × time P = .045), with an increase in the OXT group (P = .048) and no change in the placebo group (P = .406). TSH, fT4, and fT3 did not change (P ≥ .154). OXT vs placebo impacted the relationship between fT3/fT4 (6 weeks) and MHQoL (8 weeks) changes (treatment × Δ[fT3/fT4] P = .023); increased fT3/fT4 was positively associated with MHQoL improvement (trend-level P = .088). Conclusion Prolonged OXT vs placebo increased fT3/fT4 and impacted the relationship between fT3/fT4 and MHQoL changes, with a trend-level positive correlation between fT3/fT4 and MHQoL change scores. OXT action on fT3/fT4 may underpin OXT-induced mental health benefits. Clinical trial registration NCT03043053.