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MICA: Neurokinin 3 Receptor Antagonism as a Novel Treatment for Menopausal Hot Flushes

Waljit Dhillo

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Medical Research Council (MRC)
Hot flushes affect 70% of menopausal women, with up to 20% of these women describing them as 'intolerable'. Furthermore hot flushes can last up to 20 years, therefore having a significant and long-lasting effect on quality of life. Hormone Replacement Therapy is the mainstay of treatment but confers an increased risk of breast cancer, stroke and thromboembolism. Hence current guidelines recommend a limited duration of therapy and in several cases HRT is contra-indicated. Other options such as SSRIs and Clonidine are less effective than HRT. The reducing use of HRT worldwide highlights an unmet need to develop non-hormonal alternative treatments. Neurokinin B (NKB) is a recently identified hypothalamic neuropeptide. Recent studies in humans, monkeys and rodents indicate that NKB signalling within the hypothalamus mediates menopausal hot flushes. Furthermore we have recently demonstrated that administration of NKB to women elicits hot flush symptoms. We therefore hypothesise that NK3 receptor (the primary receptor for NKB) antagonism is a novel treatment for menopausal hot flushes. To test this hypothesis we propose a randomised, double-blinded, placebo-controlled, 2-way crossover study in 42 menopausal women with untreated hot flushes. Participants will receive 28 days of either oral AZD2624 or placebo in random order separated by a 14 day washout period. The primary outcome will be number of hot flushes. Secondary outcomes will include hot flush severity (FDA scale), quality of life and sternal skin conductance (measure of sweating). The study will be carried out by a team who have extensive experience in clinical trials hormonal administration and menopausal hot flushing.

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