Neurokinin receptor antagonists improve menopausal sleep disturbance

Neurokinin (NK) receptor antagonists significantly improved sleep disturbance in menopausal women compared with placebo at 4 weeks (MD −3.94; 95% CI, −5.77 to −2.11; P < 0.001), with a greater effect from dual NK1/NK3 antagonism (MD −5.24; 95% CI, −6.99 to −3.49) than from NK3-selective agents, according to results of a systematic review and meta-analysis of randomized controlled trials presented as a top-scoring abstract at The Menopause Society 2026 Annual Meeting.

Investigators evaluated the effects of NK1 and NK3 receptor antagonists, both NK1/NK3 dual and NK3-selective, on sleep disturbance in menopausal women as measured by the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS SD SF-8b) at 4, 12, and 24 weeks.

Pooling phase 2 and 3 trial data

A comprehensive search of PubMed, Embase, and the Cochrane Library identified phase 2 and 3 trials evaluating NK receptor antagonists in peri- and postmenopausal women with moderate-to-severe vasomotor symptoms that reported PROMIS SD SF-8b outcomes at 4, 12, and 24-26 weeks. Random-effects models were used to calculate pooled mean differences (MD) with 95% confidence intervals (CI). Subgroup analyses were conducted according to drug class, comparing dual NK1/NK3 with NK3-selective agents.

Dual NK1/NK3 antagonism outperformed NK3-selective agents

At 4 weeks, the effect with NK3-selective agents (MD −1.98; 95% CI, −2.79 to −1.17) was smaller than with dual antagonists, with a significant subgroup difference (P < 0.01).

At 12 weeks, the pooled effect remained significant (MD −3.15; 95% CI, −5.01 to −1.29; P < 0.001), again favoring dual NK1/NK3 antagonism over NK3-selective therapy:

• Dual NK1/NK3: MD −4.52; 95% CI, −6.34 to −2.70
• NK3-selective: MD −1.44; 95% CI, −1.89 to −0.99

The subgroup difference at 12 weeks was also significant (P < 0.01).

Benefit persisted at 24 weeks

At 24 weeks, a statistically significant overall benefit persisted (MD −2.04; 95% CI, −3.93 to −0.15; P = 0.034).

The authors reported that dual NK1/NK3 antagonism demonstrated greater short- and mid-term effects compared with NK3-selective therapy and that the findings support a clinically meaningful role for NK pathway modulation in addressing menopause-related sleep disturbance.

Reference

Lemos M, Lopes de Mattos IL, Kaunitz AM. Effects of neurokinin receptor antagonists on sleep disturbance in menopausal women: a systematic review and meta-analysis of randomized controlled trials. Poster. Presented at: The Menopause Society Annual Meeting. October 20-24, 2026. San Diego, California.