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A systematic review reported moderate evidence supporting the role of neurokinin 1/3 receptor antagonists in limiting the severity and frequency of hot flashes experienced by postmenopausal women. 

The majority of postmenopausal women experience vasomotor symptoms that include hot flashes and night sweats. However, there is limited evidence on the efficacy of non-hormonal therapies in managing vasomotor symptoms in postmenopausal women. 

This systematic review comprised a search for relevant studies in multiple electronic databases to pool evidence regarding the effectiveness of neurokinin (NK)1/3 receptor antagonists in the management of vasomotor symptoms. The findings are published in the journal Medicine

Characteristics of Included Studies 

A total of 10 studies met the inclusion criteria, which further comprised 1993 postmenopausal women. One study was a cohort study, whereas the remaining were randomized controlled trials. The women were administered oral NK3 antagonists twice a day at a dose of 40 mg. The range of treatment duration was 4–12 weeks.

Action of Neurokinin 1/3 Receptor Antagonists

The studies included in this review focused on two pharmacological agents, pavinetant and fezolinetant. The review also included NT-814, a dual NK1 receptor and NK3 receptor antagonist. Studies have shown that NK3 receptor signaling induces hot flashes in postmenopausal women, which is a potential therapeutic target focused on in this review. This also indicates that the alleviation of hot flush symptoms can be achieved without disrupting the levels of estrogen.

Efficacy of Neurokinin 1/3 Receptor Antagonists

NT-814 crosses the blood–brain barrier, occupying the receptor site for lengthy periods of time, which antagonizes NK receptor signaling. The hypothalamic effects of NT-814 counteract heat dissipation among perimenopausal women who experience hot flashes. The drug also reportedly reduces nighttime awakenings by 81%.

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Adverse Effects of Neurokinin 1/3 Receptor Antagonists

The phase 2 trial studies of NK1/3 receptor antagonists have not reported any major adverse events; however, there are concerns related to liver toxicity. A clinical trial demonstrated greater adverse events with a placebo compared to fezolinetant.

Study Limitations

This systematic review has several limitations. During the screening, the authors may have excluded relevant data due to the exclusion of discontinued studies. The included studies had a limited follow-up period of 12 weeks, which is associated with the failure to evaluate the long-term efficacy and safety of the NK1/3 receptor antagonists.


Hassan, F., Saleem, A., Samuel, S. S., Sarfraz, Z., Sarfraz, A., Sarfraz, M., & Manish, K. (2023). Neurokinin 1/3 receptor antagonists for menopausal women: A current systematic review and insights into the investigational non-hormonal therapy. Medicine, 102(23), e33978. https://doi.org/10.1097/md.0000000000033978