Neurokinin Receptor Antagonists: A Non-Hormonal Approach to Menopausal Hot Flashes and Sleep Disturbances

　　1.A New Era of Non-Hormonal Therapy for Menopausal Hot Flashes

　　Since autumn 2025,neurokinin(NK)receptor antagonists have entered the market as non-hormonal options for treating menopause-related vasomotor symptoms(VMS).Fezolinetant(Veozah;Astellas Pharma),a selective NK3 receptor antagonist,received FDA approval in May 2023.Elinzanetant(Lynkuet;Bayer),the first dual NK1/NK3 receptor antagonist,was approved by the FDA in October 2025.

　　2.NK3 vs.NK1:Mechanistic Differences Drive Distinct Clinical Benefits

　　NK3 receptors are primarily involved in thermoregulatory signaling in the hypothalamus,making NK3 antagonism directly relevant to VMS management.NK1 receptors,in addition to modest effects on vasodilation,modulate sleep through the Substance P pathway.Therefore,elinzanetant may offer added benefits for sleep beyond hot flash relief,making it particularly relevant for menopausal women experiencing concurrent sleep disturbances.Emerging research continues to explore the broader impact of NK receptor antagonism across the vasomotor symptom spectrum.

　　3.Menopausal Sleep Disturbance:Frequent Nocturnal Awakenings Are the Core Complaint

　　When discussing menopause-related sleep problems,the predominant complaint is not difficulty falling asleep initially but rather frequent awakenings after sleep onset,with prolonged periods of wakefulness during the night.This sleep maintenance difficulty significantly impairs daytime functioning and quality of life.

　　4.The NIRVANA Trial:Multimodal Assessment Confirms Sleep Improvement

　　A post-hoc analysis of the Phase 2 NIRVANA trial(NCT06112756)was presented at a 2026 medical conference.The study enrolled 110 postmenopausal women with polysomnography(PSG)-confirmed wake after sleep onset(WASO)of at least 30 minutes and at least 20 moderate-to-severe VMS episodes per week.Participants were randomized to elinzanetant 120 mg(n=55)or placebo(n=55)once daily for 12 weeks.

　　Sleep was assessed through three modalities:PSG(gold standard,two consecutive nights at baseline,Week 4,and Week 12),the Sleepiz One+contactless bedside monitor(elinzanetant group n=33;placebo group n=33),and nightly sleep diaries completed by all participants.

　　Across all three measurement methods—self-report,objective PSG,and contactless monitoring—elinzanetant significantly reduced WASO over the 12-week treatment period.These findings confirm and extend the sleep benefits previously observed in the OASIS Phase 3 program.

　　5.Individualized Care:Respecting Patient Preferences

　　As positive data for NK receptor antagonists continue to accumulate,patient preferences remain central to treatment decisions.Some women strongly decline hormone therapy;others prefer to avoid antidepressants.For these patients,non-hormonal NK receptor antagonists often represent the most appealing pharmacological option.

　　Non-pharmacological approaches should also be discussed.Cognitive behavioral therapy(CBT),for instance,has demonstrated efficacy for both vasomotor symptoms and insomnia.Clinicians should present the full range of options—pharmacological and non-pharmacological alike—to support shared decision-making and individualized management.