Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hot flushes affect 70% of menopausal women and are reported as being the most bothersome symptom by the majority. Hormone replacement therapy and other currently available alternative therapies are not without side-effects and/or have variable efficacy, and so an effective novel therapy could be practice-changing. Over the last 20 years, numerous studies in animal and human models have implicated neurokinin B, a hypothalamic neuropeptide, together with its receptor (NK3R) in the etiology of menopausal hot flushes. Most recently, a randomized, placebo-controlled trial of an NK3R antagonist in symptomatic menopausal women has proven concept suggesting a new therapeutic that can safely and effectively reduce hot flush frequency, severity, bother, and interference without the need for estrogen exposure. Here we review the physiology and neurocircuitry of the reproductive axis, hot flushes, and the evidence that supports this potential new therapeutic approach.
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PMID:Neurokinin 3 receptor antagonism - the magic bullet for hot flushes? 2904 6

Vasomotor symptoms (hot flushes, flashes, night sweats) occur in the majority of menopausal women, and are reported as being of the highest symptom priority as they often persist over many years and can be highly disruptive. Hormone therapy is the most effective available treatment but is not without risk if taken long term, and is sometimes contraindicated; for example, in women with a personal or family history of breast cancer, which is the most common female cancer worldwide. Other treatment alternatives are not as efficacious, can cause side effects, and/or are not widely available. A new, effective, targeted treatment could therefore benefit millions of women worldwide. This became possible to investigate after accumulated evidence from both animal and human models implicated heightened signaling of a hypothalamic neuropeptide together with its receptor (neurokinin B/NK3R) in the etiology of sex-steroid-deficient vasomotor symptoms. Four clinical trials of three chemically distinct oral NK3R antagonists for the treatment of menopausal flushes have since completed and published, which consistently demonstrate efficacy and tolerability of these agents. These suggest great promise to change practice in the future if ongoing further larger-scale studies of longer duration confirm the same; as, estrogen exposure will no longer be required to effectively and safely treat vasomotor symptoms.
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PMID:Neurokinin 3 receptor antagonists - prime time? 3313 40