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Visualising and controlling the cause of hot flushes at menopause

36 months
Approved budget:
Professor David Grattan
Dr Jenny Clarkson
Dr Sharon Ladyman
Health issue:
Obstetric complications/perinatal care
Proposal type:
Lay summary
Approximately 70% of women experience hot flushes during menopause. These often debilitating symptoms persist for 7 years on average, markedly reducing quality of life. Hot flushes emerge because of declining ovarian steroid levels, and while steroid hormone replacement therapy is effective, it is contraindicated for many. Neurons expressing kisspeptin are major targets of ovarian steroids, and during menopause it is hypothesised that these neurons become hyperactive in the absence of estrogen and drive the generation of hot flushes. This project aims to examine if hot flushes can be abrogated by reducing the hyperactivity of the kisspeptin neurons. We will use a state-of-the-art technique that allows us to directly observe the activity of kisspeptin neurons in conscious, freely-behaving mice, concurrently with measuring both core body and skin temperatures. We will evaluate the efficacy of several non-steroidal hormone therapies on suppressing the hyperactivity of these neurons in a low-estrogen model system.