— Meta-analysis of NK antagonist trial data shows sleep benefit as early as 4 weeks
by Rachael Robertson, Enterprise & Investigative Writer, MedPage Today
October 22, 2026 • 3 min read
Neurokinin (NK)-receptor antagonists improved sleep disturbances in menopausal women, a meta-analysis of randomized controlled trials showed.
Among women with moderate-to-severe vasomotor symptoms, the agents were associated with improvements in sleep disturbance as early as 4 weeks (standardized mean difference [SMD] -3.94, 95% CI -5.71 to -2.16) compared with placebo, reported Maria Julia Lemos, MD, of Kurah Women's Health Institute in Macaé, Brazil, and colleagues.
This trend continued at 12 weeks (SMD -3.11, 95% CI -4.60 to -1.61) and 24 weeks (SMD -2.04, 95% CI -3.93 to -0.15), Lemos reported during a presentation at the Menopause Societyopens in a new tab or window annual meeting that was co-published in Menopauseopens in a new tab or window.
"For women with hot flashes who can't or don't want to use hormone therapy, especially when poor sleep is one of their main complaints, these drugs are a good option to consider," Lemos told MedPage Today. "They may help women sleep better, not just have fewer hot flashes."
She said it's noteworthy that the benefit was seen as early as 1 month, as for many women, poor sleep is the most bothersome vasomotor symptom.
JoAnn E. Manson, MD, MPH, DrPH, of Harvard Medical School in Boston and past president of the Menopause Society, told MedPage Today that this study was rigorously conducted.
"This meta-analysis fills an important knowledge gap, as information on efficacy of treatments for vasomotor symptoms in reducing sleep disturbance has been limited," said Manson, who was not involved in the research. "This is good news for women who are seeking nonhormonal treatments for vasomotor symptoms, and especially meaningful results because of the early and sustained improvement in sleep."
Menopausal hormone therapy is the preferred treatmentopens in a new tab or window for vasomotor symptoms, but some women are contraindicated to it or may otherwise want a non-hormonal option. NK-receptor antagonists target the brain's thermoregulation center, which can help with hot flashes and improve disrupted sleep. Both fezolinetantopens in a new tab or window (Veozah) and elinzanetantopens in a new tab or window (Lynkuet) are recommended non-hormonal treatmentsopens in a new tab or window for vasomotor symptoms. Fezolinetant is an NK3 receptor antagonist, while elinzanetant is a dual NK1/NK3 receptor antagonist.
Lemos noticed that while large trials studying the agents measured sleep as a secondary outcome, there had not yet been a meta-analysis focused on sleep, which inspired this study.
For their systematic review and meta-analysis, Lemos and team searched PubMed, Embase, and Cochrane from inception to May 2026. Ultimately, seven placebo-controlled trials were included: OASIS I, II, and III; SWITCH-1; DAYLIGHT; SKYLIGHT I and II (pooled); and Depypere 2019. All trials had a low risk of bias.
Of the 3,184 women in these trials, 949 took fezolinetant, 864 took elinzanetant, and 1,371 received placebo. Mean age was 54.5 and mean body mass index was 27.7.
Five of these trials used the Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS SD-SF-8b) questionnaire, so their results were pooled. The other two trials used different questionnaires and were considered separately.
The primary outcome was change on the PROMIS SD-SF-8b scale, in which a lower score equates to less sleep disturbance. This validated questionnaire inquires about sleep quality, restfulness, and difficulty falling and staying asleep within the last 7 days.
Subgroup analyses showed that fezolinetant and elinzanetant both significantly improved sleep through 12 weeks. However, there was a greater magnitude of effect for elinzanetant at both 4 weeks (SMD -5.24, 95% CI -6.99 to -3.49 vs SMD -1.98, -2.79 to -1.17, P<0.001) and 12 weeks (SMD -4.52, 95% CI -6.34 to -2.70 vs -1.44, 95% CI -1.89 to -0.99, P=0.001).
Lemos noted some limitations, including that there were relatively few trials, that sleep disturbance was based on patient-reported outcomes, and that there was a high heterogeneity of patients, regimens, and follow-up within the included trials. It's also not possible to separate sleep benefits from vasomotor symptom relief more broadly.
Head-to-head trials comparing fezolinetant and elinzanetant are still needed, she said.