Introduction

Hot flushes/flashes (HFs) or other vasomotor symptoms affect between 45 and 97% of women during menopause. Hormone replacement therapy (HRT) is effective at alleviating menopausal symptoms, but some women cannot or prefer not to take HRT. Since current non-hormonal options have suboptimal efficacy/tolerability, there is a pressing need for an effective, well-tolerated alternative. The neurokinin 3 receptor (NK3R) has recently been implicated in the generation of menopausal HFs and represents a novel therapeutic target to ameliorate HF symptoms. This review aims to assess if NK3R antagonists (NK3Ras) are more effective than Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)—currently a common choice for non-hormonal treatment of menopausal HFs.

Methods

Studies were identified after systematically searching Ovid MEDLINE and EMBASE databases based on PRISMA guidelines. Trial quality and bias were assessed. Key efficacy outcomes (HF frequency, HF severity and number of night-time awakenings/night-sweats) and selected safety outcomes were extracted and analysed.

Results

Seven SNRI and four NK3Ra placebo-controlled randomised trials (plus four follow-up reports) were included in this review. NK3Ra administration resulted in a larger reduction from baseline in HF frequency, HF severity and night-sweats compared to SNRIs. Five of seven SNRI trials showed a reduction in HF frequency that was statistically significant (by 48–67% from baseline at weeks 8 or 12) whereas all NK3Ra trials showed a statistically significant reduction in HF frequency (by 62–93% from baseline at weeks 2, 4 or 12). While SNRI trials reported poor tolerability, particularly nausea, NK3Ra trials reported good tolerability overall, although two trials reported elevation in transaminases.

Conclusion

NK3Ras trials show encouraging efficacy and tolerability/safety. Completion of phase 3 NK3Ra trials are required to confirm efficacy and uphold safety/tolerability data but phase 2 results suggest that NK3Ras are more effective than SNRIs for non-hormonal treatment of menopausal HFs.

中文翻译：

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神经激肽 3 受体拮抗剂与血清素去甲肾上腺素再摄取抑制剂在绝经期潮热非激素治疗中的比较：系统的定性评价

介绍

潮热/潮红 (HF) 或其他血管舒缩症状影响 45% 至 97% 的绝经期女性。激素替代疗法 (HRT) 可有效缓解更年期症状，但有些女性不能或不愿服用 HRT。由于当前的非激素选择具有次优的功效/耐受性，因此迫切需要一种有效的、耐受性良好的替代品。神经激肽 3 受体 (NK3R) 最近与绝经期心衰的产生有关，是一种改善心衰症状的新治疗靶点。本综述旨在评估 NK3R 拮抗剂 (NK3Ras) 是否比血清素去甲肾上腺素再摄取抑制剂 (SNRIs) 更有效，SNRIs 目前是绝经期心衰非激素治疗的常见选择。

方法

根据 PRISMA 指南系统搜索 Ovid MEDLINE 和 EMBASE 数据库后确定了研究。评估了试验质量和偏倚。提取和分析关键疗效结果（HF 频率、HF 严重程度和夜间觉醒/盗汗次数）和选定的安全性结果。

结果

7 项 SNRI 和 4 项 NK3Ra 安慰剂对照随机试验（外加 4 份随访报告）被纳入本综述。与 SNRI 相比，NK3Ra 给药导致 HF 频率、HF 严重程度和盗汗较基线有更大的降低。七项 SNRI 试验中有五项显示 HF 频率降低具有统计学意义（第 8 周或第 12 周时从基线降低 48-67%），而所有 NK3Ra 试验均显示 HF 频率显着降低（在第 8 周或第 12 周时从基线降低 62-93%）第 2、4 或 12 周）。虽然 SNRI 试验报告耐受性差，特别是恶心，但 NK3Ra 试验报告总体耐受性良好，尽管两项试验报告转氨酶升高。

结论

NK3Ras 试验显示出令人鼓舞的功效和耐受性/安全性。需要完成 3 期 NK3Ra 试验以确认疗效并维护安全性/耐受性数据，但 2 期结果表明 NK3Ras 比 SNRIs 更有效地用于绝经期心衰的非激素治疗。