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Meta-Analysis
. 2023 Dec 15;102(50):e36592.
doi: 10.1097/MD.0000000000036592.

Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis

Ummi Aiman Rahman  1 , Talha Bin Kashif  1 , Muhammad Usman  2 , Maham Rana  2 , Muhammad Hasanain  2 , Muhammad Umair Anjum  2 , Huzaifa Ahmad Cheema  1 , Huda Jaffar  2 , Pratik Bhattarai  3
Affiliations
Meta-Analysis

Efficacy and safety of fezolinetant, a neurokinin-3 antagonist, in treating vasomotor symptoms in postmenopausal women: A systematic review and meta-analysis

Ummi Aiman Rahman et al. Medicine (Baltimore). .

Abstract

Background: Menopause causes a variety of symptoms such as hot flashes and night sweats. While menopausal hormonal therapy has been used for managing postmenopausal vasomotor symptoms (VMS) for quite a while, it has a considerably poor safety profile.

Objective: To review and analyze existing data to evaluate the efficacy of the neurokinin-3 antagonist, fezolinetant, in treating postmenopausal VMS and to assess its safety profile.

Methods: A thorough literature search was performed on PubMed, Cochrane Library, and Google Scholar in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020, to find publications on the efficacy of fezolinetant for postmenopausal VMS. Changes in the frequency and severity scores of moderate/severe VMS and changes in the Hot Flash-Related Daily Interference Scale (HFRDIS), Greene Climacteric Scale (GCS), and Menopause-Specific Quality of Life (MENQoL) were the efficacy outcomes. Adverse events, drug-related treatment-emergent adverse effects (TEAEs), drug-related dropouts, hepatotoxicity, endometrial hyperplasia or tumor, and uterine bleeding were all safety outcomes. We used Review Manager 5.4 for pooling risk ratios (RRs) and mean differences (MDs) for dichotomous and continuous outcomes, respectively. A P value of < .05 was considered significant.

Results: There was a significant reduction in mean daily VMS frequency at weeks 4 and 12 (MD, -2.36; 95% confidence interval [CI], -2.85 to -1.87; P < .00001, for week 12) and also a significant decrease in VMS severity scores in the treatment group. Furthermore, improvements in MENQoL, HFRDIS, and GCS scores were observed. There was no significant difference in adverse events while drug-related TEAEs (RR, 1.21; 95% CI, 0.90-1.63; P = .21) showed a slight increase with fezolinetant. Drug-related dropouts were again similar across the 2 groups. Uterine bleeding had a lower incidence while endometrial events and hepatotoxicity showed a statistically insignificant, increasing trend in the fezolinetant group.

Discussion and implications: Fezolinetant can be a treatment option for postmenopausal VMS but warns of a risk increase in endometrial hyperplasia or tumors. The heterogeneity in the data being analyzed, short follow-up period, and small sample size in most of the included randomized controlled trials were the greatest limitations, which must be considered in further research and safety profile exploration.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
PRISMA 2020 flow chart for the selection of eligible studies. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-analyses.
Figure 2.
Figure 2.
Assessment of study-by-study risk of bias via Cochrane Risk of Bias 2 (RoB 2) tool.
Figure 3.
Figure 3.
Forest plot for change from baseline in daily frequency of moderate/severe VMS at (A) week 4 and (B) week 12.
Figure 4.
Figure 4.
Forest plot for change from baseline in daily severity of moderate/ severe VMS at (A) week 4 and (B) week 12. VMS = vasomotor symptoms.
Figure 5.
Figure 5.
Forest plot for changes from baseline in MENQoL scores at (A) week 4 and (B) week 12. MENQoL = Menopause-Specific Quality of Life.
Figure 6.
Figure 6.
Forest plot for changes from baseline in HFRDIS scores. HFRDIS = Hot Flash-Related Daily Interference Scale.
Figure 7.
Figure 7.
Forest plot for changes from baseline in GCS scores. GCS = Greene Climacteric Scale.
Figure 8.
Figure 8.
Forest plot for any adverse event.
Figure 9.
Figure 9.
Forest plot for drug-related TEAEs. TEAEs = treatment-emergent adverse effects.
Figure 10.
Figure 10.
Forest plot for dropouts/discontinuation due to drug-related TEAEs. TEAEs = treatment-emergent adverse effects.
Figure 11.
Figure 11.
Forest plot for hepatotoxicity.
Figure 12.
Figure 12.
Forest plot for endometrial hyperplasia and tumors.
Figure 13.
Figure 13.
Forest plot for uterine bleeding.
See this image and copyright information in PMC

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