A trial of a new class of drug finds that it can reduce menopausal hot flashes by nearly three quarters within 4 weeks, and that this effect starts within 3 days of starting to take it.
The experimental compound, which was initially developed to treat schizophrenia, still needs to undergo further trials to fully evaluate its safety and effectiveness in relieving hot flashes in menopausal women.
However, the researchers are hopeful that the new class of drug will soon offer an effective alternative for women who should not or do not wish to undergo hormone replacement therapy (HRT).
The results of the trial were reported in 2017. But more recently, the researchers carried out a new analysis that looked in more detail at the time course of the drug’s effects.
The findings of the new analysis, which was led by Imperial College London in the United Kingdom, are published in the journal Menopause.
“We already knew,” says senior study author Waljit Dhillo, who is a professor in the Department of Medicine at Imperial College London, “this compound could be a game-changer for menopausal women and get rid of three quarters of their hot flashes in 4 weeks.”
“But this new analysis,” he continues, “confirms the beneficial effect is obtained very quickly — within just 3 days.”
The menopause is a stage in a woman’s life in which her periods stop and her level of the hormone estrogen — which is produced by the ovaries — begins to decline and she loses her ability to become pregnant naturally. This typically occurs between the ages of 45 and 55.
“Hot flashes” is a common term for the recurring, temporary episodes of “vasomotor symptoms,” in which women approaching and going through menopause experience flushing, hot sensations in the face and upper body.
In the United States, around three quarters of all menopausal women report experiencing hot flashes.
Some women will feel hot flashes as no more than annoyances or embarrassments, but for many others, the episodes can be very uncomfortable, causing clothes to become drenched in sweat.
Hot flashes can also occur at night, during sleep, and therefore result in night sweats. In some cases, the symptoms are severe enough to impact quality of life.
Each woman’s experience of hot flashes tends to follow a pattern that is unique to her. Typically, their frequency increases as she approaches the menopause, then reaches a peak for around 2 years after the menopause and gradually wanes thereafter.
The experience of hot flashes can last from 6 months to 5 years, although in some cases, they can linger for 10 years or longer.
HRT has helped to ease the symptoms of the menopause in many women. However, because it is based on estrogen, it is not without risk.
The new paper describes how an experimental compound — referred to as MLE4901 — was tested in a randomized, double-blind, and placebo-controlled trial. The participants were 37 menopausal women of age 40–62 who were having at least seven hot flashes per day.
The team randomly assigned the women to receive a 4-week course of either a daily 80-milligram dose of the drug or a placebo.
After the 4 weeks, the women then switched over, so that those on the drug then took the placebo and those on the placebo then took the drug, for another 4 weeks.
The results revealed that when they were taking the experimental drug, the women experienced, on average, fewer hot flashes over the 4 weeks, when compared with the average number experienced over the 4 weeks when they took the placebo.
But an equally important trial result — which became apparent when the researchers carried out the new time-course analysis — was that the compound began to show a “significant effect” within just 3 days.
For example, by day 3 of treatment with the drug, the frequency of the hot flashes reduced by 72 percent “compared with baseline” and showed a “51 percentage point reduction compared with placebo,” note the study authors.
The size of this effect “persisted throughout the 4-week period,” they add, further observing that the drug also reduced severity of hot flashes by 38 percent by day 3.
Prof. Dhillo says that because MLE4901 has side effects that impact the liver, it will be other drugs with the same action that will be tested further in trials. One trial has already started in the U.S.
The researchers think that the compounds work by inhibiting neurokinin B (NKB), a substance in the brain that previous studies in animals and humans have suggested may trigger hot flashes.
The new analysis also found that the new drug relieved daytime hot flashes as well as night-time ones.
Also, the women reported that the number of hot flashes that disrupted their sleep at night fell by 82 percent and that they experienced 77 percent less impairment to concentration when on the drug.
However, the researchers could not say whether these further improvements were a result of fewer hot flashes or a direct result of the compound’s effect on the brain.
They are hopeful, nevertheless, that the drug may directly improve many menopausal symptoms — from hot flashes to sleeping disruption and impaired concentration, and even weight gain — because of the many parts of the brain affected by NKB.
Prof. Dhillo notes that the trial has enabled them to find a “new therapeutic use for the compound — which had previously been sitting on the shelf unused” — and that they expect that within 3 years, it will be making “a tangible difference to the lives of millions of women.”
“This class of new drugs may provide women with a much-needed alternative to HRT.”
Prof. Waljit Dhillo