Many women think of the menopause with dread, associating it with uncontrolled body temperature and hormonal shifts. In fact, 1 in 10 women report hot flushes as intolerable, severely impairing their quality of life and daily wellbeing. The most widespread solution to counteract menopausal flushes is oestrogen supplementation (also known as hormone replacement therapy, HRT) which often is not a sustainable solution due to serious long term health concerns, such as increased risk of breast and ovarian cancers, thromboembolism, and stroke. However a recent causative implication of hypothalamic neurokinin B and its receptor NK3R in hormone release and regulation of body temperature offers a promising targeted solution for this symptom of menopause.
Professor Waljit Dhillo and colleagues in the NIHR Imperial Biomedical Research Centre (BRC) have previously demonstrated that injecting pre-menopausal women with neurokinin B induced hot flushes, thus mimicking symptoms of post-menopausal women. They predicted that pharmacological blockade of neurokinin B receptor would be an effective novel strategy to combat menopausal flushes, without the need for potentially hazardous oestrogen exposure.
Such blockers have already been developed and their safety established. The resulting phase II trial of an NK3R inhibitor MLE4901 was led by NIHR Research Professor Dhillo, with infrastructure support from the NIHR Imperial BRC. The study demonstrated substantial improvements in the wellbeing of women with severe or bothersome hot flushes. Published in The Lancet and gaining significant press coverage, the study reported a reduction in the weekly number of hot flushes by 73% in women taking MLE4901 compared to no treatment, and by 45% when compared with placebo. Twice daily oral administration of MLE4901 significantly reduced severity, bother and interference of hot flushes, and these women also reported improvements in sleep-related symptoms, such as fatigue and irritability.
Although larger and longer studies are required, this novel practice-changing targeted therapeutic approach could benefit an estimated 10 million women in the UK alone, and transform their daily lives without a need for increased exposure to oestrogen or combination with other substances.