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New non-hormonal treatment in development for flushes

29 June 2020

Menopausal hot flushes and sweats affect around 80% of women, can cause significant distress and can last for many years. Hormone Replacement Therapy is recommended as first line treatment, but is not appropriate nor desired by all women with symptoms. This is especially relevant to women who have had hormone dependant cancer. Non hormonal treatments can be prescribed but many are unlicensed for this indication, have variable effectiveness and may have side effects.

Recent research has been shown that a chemical pathway involving neurokinin B/ neurokinin-3-receptor (NKB/NK3R) is involved in the development of hot flushes, interacting with the temperature controlling centre in the brain. Neurokinin B binds to the neurokinin-3-receptor to stimulate its effects. In postmenopausal women, estrogen deficiency increases neurokinin B so that the pathway is overstimulated, leading to flushes and sweats. Therefore, agents which act against neurokinin-3-receptor (NK3R antagonists) could suppress the pathway and reduce flushes and sweats.

One such antagonist, NT-814, has shown promising results. A two-week randomised study comparing NT-814 and placebo showed reduction in hot flush frequency by 84% compared to 39% in the placebo group, and waking due to night sweats reduction by 81% (vs 32% placebo) [1].

NT-814 has now been tested in a further randomized, double-blind, placebo-controlled 12-week study in menopausal women. This study showed that NT-814 significantly reduces hot flush frequency, improves sleep, mood and quality of life with no safety concerns [2].

Further studies are required and are underway, but the possibility of an effective, safe non-hormonal option for women who cannot, or prefer not to take HRT is an exciting prospect for the future.

References

  1. Trower M, Anderson RA, Ballantyne E, Joffe H, Kerr M, Pawsey S. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause. 2020;27(5):498-505. https://pubmed.ncbi.nlm.nih.gov/32068688/

  2. Simon J, Anderson -RA, Ballantyne E, Joffe H, Kerr M, Seymore S, Trower M, Pawsey S. OR11-03 NT-814, a Non-Hormonal Dual Neurokinin 1,3 Receptor Antagonist Markedly Improves Vasomotor Symptoms in Post-Menopausal Women; Results of a Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Study (SWITCH-1), Journal of the Endocrine Society, Volume 4, Issue Supplement_1, April-May 2020, OR11-03.

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