Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: a comprehensive systematic review and meta-analysis of randomized controlled trials

Majd M AlBarakat; Jehad Feras AlSamhori; Ahmed Abdelaziz; Amr Elrosasy; Mohamad A Elzeftawy; Rana Ahmed Youssef; Rana B Altawalbeh; Mohamed Abuelazm; Basel Abdelazeem

doi:10.1080/08998280.2025.2491894

Efficacy and safety of fezolinetant for vasomotor symptoms in postmenopausal women: a comprehensive systematic review and meta-analysis of randomized controlled trials

Proc (Bayl Univ Med Cent). 2025 Jun 17;38(4):535-546. doi: 10.1080/08998280.2025.2491894. eCollection 2025.

Authors

Majd M AlBarakat¹, Jehad Feras AlSamhori², Ahmed Abdelaziz³, Amr Elrosasy⁴, Mohamad A Elzeftawy⁵, Rana Ahmed Youssef⁶, Rana B Altawalbeh¹, Mohamed Abuelazm⁵, Basel Abdelazeem⁷

Affiliations

¹ Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
² School of Medicine, The University of Jordan, Amman, Jordan.
³ Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
⁴ Faculty of Medicine, Cairo University, Cairo, Egypt.
⁵ Faculty of Medicine, Tanta University, Tanta, Egypt.
⁶ Faculty of Medicine, Alexandria University, Alexandria, Egypt.
⁷ Department of Cardiology, West Virginia University, Morgantown, West Virginia, USA.

Abstract

Introduction: Approximately 360 million women globally experience hot flashes, with varying rates influenced by cultural and racial factors. Vasomotor symptoms (VMS) impact 80% of US women during menopause, with emerging risk factors including high body mass index and African American ancestry. Fezolinetant, an oral neurokinin-3 receptor antagonist, showed promising efficacy in managing VMS. We aimed to comprehensively assess the impact of fezolinetant on VMS in postmenopausal women.

Methods: We searched PubMed, Cochrane, Web of Science, SCOPUS, and EMBASE until July 2023 for randomized controlled trials comparing fezolinetant to placebo in women with moderate to severe VMS. Primary outcomes encompassed VMS frequency and severity, and secondary outcomes included treatment effects, quality of life, and safety. Data were collected and analyzed using STATA 17 MP.

Results: We included six studies with 3657 patients. Fezolinetant significantly reduced VMS frequency at both 4 weeks (Cohen's d = -0.56; 95% confidence interval [CI], -0.79, -0.34; P < 0.001) and 12 weeks (Cohen's d = -0.34; 95% CI, -0.45, -0.14; P < 0.001). In terms of secondary outcomes, fezolinetant significantly improved health-related functioning and global clinical summary scores, particularly with the 90 mg twice per day dosage. Crucially, there were no statistically significant differences between fezolinetant and placebo concerning the occurrence of any treatment-emergent (odds ratio [OR] = 1.01, P = 0.81) or serious (OR = 1.57, P = 0.90) adverse events.

Conclusion: Fezolinetant effectively reduces VMS in postmenopausal women at both 4 and 12 weeks, aligning with previous research. It also improves quality of life, with a promising safety profile. Given fezolinetant's potential for liver enzyme elevations, it is essential to monitor liver function at baseline and regularly thereafter (monthly for the first 3 months and at 6 and 9 months) to ensure patient safety. Further studies with larger sample sizes are needed to confirm these findings.

Keywords: Fezolinetant; postmenopausal; vasomotor symptoms.