In a trial carried out at Imperial College London, researchers showed that women who suffered seven or more hot flushes a day could reduce the number by as much as 73%, as well as reducing their severity and impact.
HRT can be an effective treatment for some women but may not be suitable for everyone. The therapy, which involves taking regular oestrogen supplements to relieve symptoms, may increase the relative risk of breast cancer and can increase the risk of blood clots. This means that many women cannot take HRT to relieve their menopausal symptoms.
The team hopes that this successful early-stage study, involving a drug which targets receptors in the brain, could provide hope for women who are affected by hot flushes and for whom hormone replacement therapy (HRT) is either unsuitable or not preferred by the patient due to safety concerns.
In the latest study, which was funded by the MRC and NIHR and led by Professor Dhillo, 28 women with severe flushing were given a new drug compound called MLE4901, originally developed by AstraZeneca and licensed to Millendo Therapeutics, to try to relieve their symptoms.
Clinical model
At the heart of the approach is blocking a chemical called neurokinin B (NKB). Previous studies in animals revealed that increased levels of the chemical caused a flushing response in the tails of rats similar to a menopausal flush.
In human studies, analysis of brain tissue from post-menopausal women revealed elevated levels of NKB in their brains. The Imperial team has previously found that giving NKB to younger women in a temperature-controlled room caused flushing.
Bringing together all of these strands led the researchers to think that blocking the action of the chemical could potentially have the opposite effect and be a new effective treatment for menopausal flushing.
To test the idea, female volunteers with frequent flushing were administered MLE4901 which blocks the NK3 receptors of the brain, where NKB acts, to suppress the action of the chemical.
Trial specifics
In a randomised, double-blind, placebo-controlled trial, menopausal women aged between 40 and 62 years old – and who experienced seven or more hot flushes a day and had not had a period in at least 12 months – were recruited at Imperial College Healthcare NHS Trust hospitals.
Participants were randomly chosen to either first receive a 80 mg daily dose of the drug or a placebo over the course of a four week period, before switching to receive the other tablet for an additional four weeks. This ensured the women acted as their own controls during the study, and the effects of the drug were clear.
Dr Julia Prague, first author of the study, commented, "Despite the fact that for millions of women their menopausal symptoms are intolerable so many are suffering in silence because it is a taboo subject and treatment options are limited."
Professor Dhillo concluded: "This was a proof of concept study and proves that an NK3R blocker, MLE4901, significantly reduces menopausal flushing by 73% during a four-week treatment period. These are exciting findings which could be practice-changing. The plan now is to find out if the NK3R blocker, MLE4901, can be as safe and effective over a long term period in a larger group of patients."
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