SUN-149 - OPTION‑VMS: Preliminary Analysis of A Phase 4 Observational, Real‑World Study of Non‑Hormonal Pharmacotherapies for Bothersome Menopause‑Associated Vasomotor Symptoms and Depression and Anxiety

Introduction
Vasomotor symptoms (VMS) can significantly impact sleep , mood, quality of life, and overall functioning. Depression/anxiety risk increases in menopause, especially in women with frequent/severe VMS. There is a complex interrelatedness between VMS, sleep, and mood, with VMS linked to disrupted sleep and higher depression/anxiety risk.

Fezolinetant 45 mg once daily is a globally-approved, effective non-hormonal therapy (non-HT) for moderate to severe VMS due to menopause. We present preliminary findings on changes in VMS bother and depression/anxiety symptoms from OPTION-VMS, the first real-world study on fezolinetant, SSRIs/SNRIs, and other non-HT in women with bothersome VMS.

Objective
To evaluate within‑group changes in VMS bother and mood via depression/anxiety symptoms in women initiating non-HT for bothersome VMS.

Methods
OPTION-VMS (NCT06049797) is an ongoing, phase 4, longitudinal, multicenter, observational study of women aged 40-75 years with bothersome menopausal VMS initially prescribed non-HT (fezolinetant, SSRIs/SNRIs, and other non-HTs [eg, gabapentin, oxybutynin]). Within-group changes from baseline to week 12 were assessed for VMS bother (primary endpoint; MENQOL VMS domain) and at week 4 for depression/anxiety symptoms (exploratory; PHQ‑9 and GAD‑7 total scores).

Results
The sample included 656 participants. In the fezolinetant group (n=201), statistically significant improvements from baseline to week 12 in VMS bother (MENQOL VMS domain, LS mean change of -2.79 [95% CI -3.48, -2.10; P< 0.001]) were observed (primary endpoint).

In the fezolinetant group, statistically significant improvements in depression/anxiety symptoms at week 4 were also observed: LS mean change from baseline of -3.45 for PHQ‑9 (95% CI -4.90, -2.01; P< 0.001), -2.32 for GAD‑7 (95% CI -3.61, -1.02; P< 0.001).

While not a comparative study, SSRIs/SNRIs (n=329) and other non‑HT (n=126) groups showed significant improvements from baseline to week 4 in depression/anxiety symptoms: LS mean changes from baseline of -3.18 and -2.78 for PHQ‑9, -1.97 and -1.43 for GAD‑7, respectively (all P< 0.05).

Statistically significant improvements from baseline were observed in depression/anxiety symptoms at weeks 8 and 12 (all groups P< 0.05).

Conclusions
Preliminary analysis of OPTION VMS showed improvements in VMS bother and depression/anxiety symptoms with non-HT use, including fezolinetant. Results align with randomized controlled trial data of fezolinetant, highlighting real-world benefits beyond VMS relief, including improvements in depression/anxiety symptoms.

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