ReviewFrontiers in neuroendocrinology2013
Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes.
Review in Frontiers in neuroendocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07042516 (Safety and Efficacy of Asimadoline), which is not on this map. Cited by 170 papers, 8 of them syntheses that pooled 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.
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.
Safety and Efficacy of Asimadoline (TP0052), a Peripherally Restricted Selective Kappa Agonist, for the Treatment of Moderate to Severe Menopausal Symptoms in Midlife Women.
Who cites it
170 citing papers in PubMed, 8 syntheses or guidelines pooled it, 349 citations in OpenAlex.
- Vasomotor Symptoms and Their Association with Depressive and Anxiety Symptoms in Peri- and Postmenopausal Women: A Systematic Review of Observational Studies.Medicina (Kaunas, Lithuania) · 2026Pooled it
- Elinzanetant: Efficacy and safety in the management of vasomotor symptoms in postmenopausal women, a systematic review and meta-analysis with grading of recommendations assessment, development, and evaluation assessment.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Pooled it
- Fezolinetant's efficacy and safety in treatment of vasomotor symptoms in postmenopausal women: a meta-analysis and GRADE evaluation of randomized controlled trials.European journal of medical research · 2025Pooled it
- Effect of acupuncture on menopausal depressive disorder and serum hormone levels: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Neurokinin 3 Receptor Antagonists Compared With Serotonin Norepinephrine Reuptake Inhibitors for Non-Hormonal Treatment of Menopausal Hot Flushes: A Systematic Qualitative Review.Advances in therapy · 2021Pooled it
- Genetic Variation and Hot Flashes: A Systematic Review.The Journal of clinical endocrinology and metabolism · 2020Pooled it
- Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review.BJOG : an international journal of obstetrics and gynaecology · 2020Pooled it
- Effect of acupuncture on hot flush and menopause symptoms in breast cancer- A systematic review and meta-analysis.PloS one · 2017Pooled it
- Trial
- Efficacy and safety of GS1-144, a novel neurokinin 3 receptor antagonist, for moderate-to-severe vasomotor symptoms associated with menopause in Chinese women: a randomized, double-blind, placebo-controlled phase 2 trial.Menopause (New York, N.Y.) · 2026Trial
- Validation and Application of Thresholds to Define Meaningful Change in Vasomotor Symptoms Frequency: Analysis of Pooled SKYLIGHT 1 and 2 Data.Advances in therapy · 2024Trial
- Efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms associated with menopause among women in East Asia: a phase 3 randomized study (MOONLIGHT I).The Journal of international medical research · 2024Trial
- Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.The Journal of clinical endocrinology and metabolism · 2023Trial
- Q-122 as a novel, non-hormonal, oral treatment for vasomotor symptoms in women taking tamoxifen or an aromatase inhibitor after breast cancer: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet (London, England) · 2022Trial
- Trial
- Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men.The Journal of clinical endocrinology and metabolism · 2020Trial
- Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA).Menopause (New York, N.Y.) · 2020Trial
- Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial.Menopause (New York, N.Y.) · 2020Trial
- A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause.Menopause (New York, N.Y.) · 2020Trial
- Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.Lancet (London, England) · 2017Trial
110 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Despite affecting millions of individuals, the etiology of hot flushes remains unknown. Here we review the physiology of hot flushes, CNS pathways regulating heat-dissipation effectors, and effects of estrogen on thermoregulation in animal models. Based on the marked changes in hypothalamic kisspeptin, neurokinin B and dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy neurons play a role in the mechanism of flushes. In the rat, KNDy neurons project to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R), the primary receptor for NKB. Furthermore, activation of NK₃R in the median preoptic nucleus, part of the heat-defense pathway, reduces body temperature. Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation. These data suggest that arcuate KNDy neurons relay estrogen signals to preoptic structures regulating heat-dissipation effectors, supporting the hypothesis that KNDy neurons participate in the generation of flushes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.