Journal of South Asian Federation of Obstetrics and Gynaecology · Feb 2, 2026

Pioneering a New Era in Menopause Care—A Novel, Promising, and Future-oriented Role of NK3R Antagonists as a Nonhormonal Therapy: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

By Adella CA, Khosasi F, Elbert E

Aims and background: Declining estrogen levels during menopause trigger vasomotor symptoms (VMSs) like sudden warmth and drenching night sweats, potentially diminishing overall well-being.While hormone therapy (HT) is effective, its use may be restricted by medical or personal factors, highlighting the need for alternative treatments.Neurokinin 3 receptor (NK3R) antagonists target neurokinin B pathways to relieve VMS.This meta-analysis reviews randomized controlled trials (RCTs) to assess their safety and efficacy, intended to support clinical recommendations and advance encouraging nonhormonal therapies for menopausal symptom relief.Methods: This systematic review and meta-analysis, based on PRISMA 2020, assesses the efficacy and safety of NK3R antagonists in treating menopausal VMSs.A literature search (2018-2025) was conducted in EMBASE, PubMed, Scopus, Cochrane, and Web of Science to identify relevant RCTs.Methodological quality was evaluated using the RoB-2 tool.Statistical analyses (MD and pooled proportions with 95% CI) were performed using Review Manager 5.4 and R (v4.4.2).To determine heterogeneity, the I² statistic was employed, and analyses were conducted using fixed-or random-effects models as appropriate.Publication bias was explored through funnel plot symmetry, the Trim-and-Fill procedure, and Egger's regression analysis.Results: Neurokinin 3 receptor antagonists demonstrated a significant reduction in the frequency of hot flashes [(mean difference) MD: -2.30; p = 0.0005] and their severity (MD: -0.19; p = 0.03).There was also a notable improvement in Menopause-specific Quality of Life Questionnaire (MENQoL) scores (MD: -0.39; p < 0.00001) and in sleep disturbances (MD: -3.23; p < 0.00001).Overall, 46.3% experienced treatment-emergent adverse events (TEAEs), of which 20.1% were attributed to the treatment and 4.7% were identified as serious.No severe adverse events or deaths were reported, supporting a positive overall safety assessment.Conclusion: Neurokinin 3 receptor antagonists effectively reduce VMSs in menopausal women by decreasing hot flash frequency and severity.They improve overall well-being (MENQoL), sleep quality (PROMIS B), and reduce anxiety.With a favorable safety profile and minimal adverse effects, they provide a potential alternative to HT for menopausal symptom management.Clinical significance: Neurokinin 3 receptor antagonists are beneficial in mitigating vasomotor disturbances such as hot flashes and night sweats during menopause.They also improve sleep and quality of life, with few serious side effects.Offering a nonhormonal and well-tolerated approach, these drugs are suitable for women who do not wish to use HT.

doi.org/10.5005/jp-journals-10006-2694 Open access Interventions