Experimental Drug Substantially Reduces Menopausal Hot Flushes

An investigational drug compound shows promise in the treatment of patients experiencing hot flushes brought on by menopause. A study published by The Lancet suggests that the novel drug could reduce the number of hot flushes by 73%, and reduce its severity and impact.

The study authors hope that these findings could provide hope to patients who experience significant hot flushes and for those who cannot receive hormone replacement therapy (HRT).

"If a woman is having more than 7 flushes a day and the drug is getting rid of three-quarters of them, that's pretty life-changing,” said researcher Waljit Dhillo, PhD. "For day to day living and work, that's a significant impact on quality of life. If we can reduce flushing by 73% it's a game-changer for those patients."

During menopause, the body stops making estrogen, which causes the onset of hot flushes and sweating. For some women, this change may be mildly inconvenient, but others may experience severe symptoms that can impact work, social, and home life.

HRT is an effective therapy that involves taking estrogen supplements; however, it may increase the risk of breast cancer and blood clots, making it unsafe for certain patients.

Included in the current study were 28 women experiencing severe menopause-related flushes. These women were treated with MLE4901, a novel drug that targets the neurokinin 3 (NK3) receptors in the brain, to relieve symptoms.

Previous animal studies showed that increased levels of the chemical neurokinin B (NKB) resulted in a flushing response in rats. In human studies, brain tissue from post-menopausal women showed high levels of NKB. Additionally, the team of researchers discovered that giving NKB to young women caused flushing.

These findings caused the study authors to speculate that blocking NKB could potentially reduce flushing, and present a novel treatment for patients experiencing symptoms of menopause.

Patients were randomized to receive 80-mg of MLE4901 daily or a placebo over 4 weeks and then switched to receive the other treatment for an additional 4 weeks. Since the patients were their own controls, the authors said the efficacy of the drug was clear, according to the study.

The authors reported that treatment with MLE4901 was linked to a reduction in the occurrence and severity of hot flushes compared with placebo. It also reduced the impact of the hot flushes, and improved sleep among patients, according to the study.

“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,” said first author Julia Prague, MBBS, BSc, MRCP. "It was so exciting to see the lives of those who participated in the study become transformed when their flushes improved once taking the new drug. They could sleep through the night, and be less embarrassed in the daytime; they told me they felt 'human again.'"

One of the study participants said that she was interested in participating because a successful treatment could significantly improve the lives of women undergoing menopause. She noted a significant improvement in quality of sleep when taking MLE4901.

Treatment with an NK3 receptor blocker would be considered much safer for patients who cannot receive HRT over concerns of breast cancer and blood clots.

"A lot of women are choosing not to take HRT because it is oestrogen [sic]-based,” Dr Dhillo said. “This new drug is a pill which blocks the NK3 receptor, so it won't have the side effects associated with oestrogen [sic]."

An additional, potentially safer treatment option offered to menopausal women could dramatically improve quality of life, according to the authors. Further studies will aim to confirm these findings.

"This was a proof of concept study and proves that an NK3R blocker, MLE4901, significantly reduces menopausal flushing by 73% during a 4-week treatment period,” Dr Dhillo concluded. "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."