Effects of neurokinin receptor antagonists on sleep disturbance in menopausal women: a systematic review and meta-analysis of randomized controlled trials

Importance: Sleep disturbance is a common and burdensome symptom among perimenopausal and postmenopausal women with moderate to severe vasomotor symptoms (VMS). Although neurokinin (NK) receptor antagonists have demonstrated efficacy for reducing VMS, their effects on sleep disturbance remain incompletely characterized. Objective: To evaluate the effects of NK receptor antagonists on sleep disturbance in perimenopausal and postmenopausal women with moderate to severe VMS. Evidence Review: A systematic review and meta-analysis of randomized controlled trials was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) and Cochrane recommendations. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through May 2026. Eligible studies enrolled perimenopausal or postmenopausal women with moderate to severe VMS and compared NK receptor antagonists with placebo. The outcome of interest was change in the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form 8b scores at 4, 12, and 24 weeks. Random-effects meta-analyses were performed using standardized mean differences (SMDs) and 95% CIs. Risk of bias was assessed using Risk of Bias 2, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Trial sequential analysis was performed to assess the robustness of cumulative evidence. Findings: Seven randomized controlled trials involving 3,184 women were included. NK receptor antagonists were associated with significant improvements in sleep disturbance compared with placebo at 4 weeks (SMD: −3.94; 95% CI: −5.71 to −2.16; 5 studies; 2,869 participants), 12 weeks (SMD: −3.11; 95% CI: −4.60 to −1.61; 5 studies; 2,869 participants), and 24 weeks (SMD: −2.04; 95% CI: −3.93 to −0.15; 4 studies; 1,798 participants). Subgroup analyses demonstrated significant benefits for both elinzanetant and fezolinetant, with a greater magnitude of effect observed for elinzanetant ( P < 0.001). All included studies were judged to have low risk of bias. However, certainty of evidence was rated as low because of substantial unexplained heterogeneity. Trial sequential analysis demonstrated that the accumulated evidence crossed monitoring boundaries and reached the required information size for all primary outcomes. Conclusions and Relevance: NK receptor antagonists significantly improved patient-reported sleep disturbance among perimenopausal and postmenopausal women with moderate to severe VMS. These findings support NK receptor antagonists as a promising nonhormone treatment option for VMS-associated sleep disturbance, although the magnitude of benefit should be interpreted cautiously because of substantial heterogeneity and low-certainty evidence.