Evidence map›Paper›PMID 34514552›Full record

SynthesisAdvances in therapy2021

Neurokinin 3 Receptor Antagonists Compared With Serotonin Norepinephrine Reuptake Inhibitors for Non-Hormonal Treatment of Menopausal Hot Flushes: A Systematic Qualitative Review.

Sara J Menown, Javier A Tello

Open access · hybridAbstract readSystematic Review
In one paragraph

Synthesis in Advances in therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Menopause and gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  4. Effects of menopause on temperature regulation.Temperature (Austin, Tex.) · 2025
    Review
  5. Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data.Current neurology and neuroscience reports · 2024
    Review
  6. Article
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Sara J MenownSchool of Medicine, University of St Andrews, Medical and Biological Sciences Building, North Haugh, St Andrews, KY16 9TF, UK.
Javier A TelloSchool of Medicine, University of St Andrews, Medical and Biological Sciences Building, North Haugh, St Andrews, KY16 9TF, UK. jt65@st-andrews.ac.uk.ORCID http://orcid.org/0000-0001-6637-2155
University of St Andrews · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionHot 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.

methodsStudies 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.

resultsSeven 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.

conclusionNK3Ras 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.

Indexed as

Selective Serotonin Reuptake InhibitorsSerotoninFemaleHumansMenopauseNorepinephrineReceptors, Neurokinin-3NorepinephrineReceptors, Neurokinin-3Selective Serotonin Reuptake InhibitorsSerotoninDesvenlafaxineElinzanetant (NT-814)FezolinetantHot flushes/flashesMenopauseMLE4901Neurokinin 3 receptor antagonistSerotonin Norepinephrine Reuptake InhibitorVasomotor symptomsVenlafaxine

Identifiers

PMID34514552
PMCPMC8478773
OpenAlexW3201251727

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.