MON-126 - Higher Plasma Oxytocin and Vasopressin Levels May Reflect Chronic Stress in Menstrually Related Mood Disorders

Background: Menstrually related mood disorder (MRMD) is characterized by severe psychological symptoms in the late luteal phase of the menstrual cycle. Lower oxytocin (OT) and higher vasopressin (VP) levels have been associated with worse depressive and anxiety symptoms; however, no study has investigated OT and VP levels in MRMD, and it is possible that they contribute to MRMD psychopathology. In MRMD vs. healthy controls (HC), we aimed to investigate (A) OT levels across the menstrual cycle; (B) changes in OT levels from mid-follicular to late-luteal phase; and (C) whether OT levels are associated with affective symptoms. We hypothesized that late-luteal OT levels (primary endpoint) would be lower in MRMD vs. HC participants, and that lower OT levels would be associated with worse affective symptoms (key secondary endpoint). In addition, we hypothesized that VP levels would be higher in MRMD vs. HC, and higher VP levels would be associated with worse affective symptoms (exploratory endpoints).

Methods: Fasting plasma OT and VP levels were collected in 9 women with MRMD and 14 HC in the mid-follicular (cycle day 6-10), mid-luteal (5-9 days after ovulation), and late luteal phase (9-13 days after ovulation) of the menstrual cycle. Participants were not on psychotropic medications. MRMD physical and psychological (Daily Record Severity of Problems, DRSP), depressive (Quick Inventory of Depressive Symptomatology, QIDSSR), and anxiety (General anxiety disorder-7, GAD-7) symptoms were assessed at each visit (higher scores reflect worse symptoms).

Results: Follicular-phase age and BMI did not differ across groups (p>0.100). Depressive symptoms were worse in MRMD than HC in the late luteal phase only, as expected (P < 0.001). In both groups, OT increased from follicular to late luteal phase (p=0.001). At all timepoints, OT was higher in the MRMD group (p=0.041). From mid- to late luteal phase, OT increased in MRMD vs. HC (time*group p=0.005). Late-luteal OT levels were higher in MRMD vs. HC ([meanSEM] 500.941.6 vs. 361.929.6 pg/mL, p=0.010) and were positively associated with DRSP (ρ=0.54; p=0.012); QIDSSR (ρ=0.45; p=0.036), and GAD-7 (ρ=0.41; p=0.056, trend) scores in the late luteal phase. VP levels were higher in MRMD than HC at all timepoints (p=0.014) and did not correlate with symptom scores (p>0.229).

Conclusions: Contrary to our hypotheses, MRMD had higher OT levels across the menstrual cycle than HC and a significant increase in OT levels from mid to late luteal phase. In the whole group, higher OT levels were associated with more severe MRMD physical, psychological, depressive, and anxiety (trend-level) symptoms. VP levels were also higher in MRMD than HC across the menstrual cycle. Elevated OT and VP may represent a compensatory response to depressive symptoms and/or be markers of chronic stress in MRMD.

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