Women who can’t or choose not to take hormones to relieve hot flashes, a common symptom in menopause, have always been forced to consider other, far less effective treatments. But now there is a new alternative.
The US Food and Drug Administration (FDA) has approved fezolinetant (Veozah), a non-hormonal medicine for hot flashes. Developed by Astellas Pharma, this is the second non-hormonal drug licensed for hot flashes in the US and research to date suggests it will be helpful in reducing hot flashes and night sweats.
We need better nonhormonal therapies for those women who can’t or choose not to take hormone therapy, says JoAnn Pinkerton, MD, professor of obstetrics and gynecology and director of the Midlife Health Center at the University of Virginia Health at charlottesville.
More than a million American women go through menopause each year, according to a book published by StatPearls in 2022. This happens when estrogen levels drop and women stop menstruating.
As production of the hormones estrogen and progesterone decreases in the years leading up to and after menopause, a wide range of symptoms can occur, including mood swings, joint pain, vaginal dryness, insomnia, and memory problems. Vasomotor symptoms, or hot flashes and night sweats, occur in about 75 percent of menopausal women, according to the North American Menopause Society (NAMS).
While the exact cause of hot flashes and night sweats isn’t known, reduced levels of estrogen are thought to interfere with normal body temperature regulation processes in the brain, says Dr. Pinkerton.
Fezolinetant is the first drug in a new family of drugs known as neurokinin 3 receptor antagonists, designed to block the activity in the hypothalamus region of the brain that causes the body’s internal thermostat to malfunction.
People prescribed Veozah should take one 45-milligram (mg) pill, once a day, with or without food. The pill should be taken at the same times each day, according to the FDA press release. Veozah will be available in pharmacies within the next three weeks, and the pill will cost $550 for a month’s supply, according to the company. They also plan to offer a financial support program to make the drug more affordable.
How Fezolinetant works
In a key study of late-stage fezolinetant published in February 2023 in Journal of Clinical Endocrinology and Metabolism, researchers randomly assigned 500 menopausal women to take either a placebo or a 30 or 45 mg fezolinetant pill. All had an average of at least seven moderate to severe hot flashes per day when they joined the study.
After 12 weeks of treatment, the average daily number of hot flashes dropped from 11.2 to 4.8 for people on the lowest dose of fezolinetant, eliminating an average of 1.9 more daily episodes compared to placebo. Participants on the highest dose of fezolinetant saw their average number of daily hot flashes drop from 11.8 to 4.5, eliminating 2.5 more episodes than on placebo.
A separate late-stage study published in Hand in March found similar results in about 525 participants with moderate to severe hot flashes who were randomly assigned to take a placebo or one of the same two doses of fezolinetant for 12 weeks. Compared with a placebo, the average daily number of hot flashes decreased by 2.4 more with the lowest dose of fezolinetant and by 2.6 more with the highest dose.
No studies have tested fezolinetant directly against hormones for hot flashes. But the results of fezolinetant’s late-stage studies suggest that this drug may work almost as well as hormones to reduce the frequency and severity of hot flashes, Pinkerton says. Fezolinetant is also significantly more effective than the only other FDA-approved nonhormonal drug for hot flashes, paroxetine (Brisdelle), Pinkerton adds, although these drugs haven’t been studied head-to-head.
Paroxetine belongs to a family of medicines known as selective serotonin reuptake inhibitors (SSRIs) that were originally developed to treat depression. It can eliminate about one more hot flash per day than a placebo, according to an analysis published in British Journal of Obstetrics and Gynecology. The FDA approved the drug even though an independent FDA advisory committee advised against approval due to its limited efficacy.
Is Fezolinetant safe?
A year-long safety study with more than 1,800 participants found that most side effects of fezolinetant were mild or moderate, according to findings published in April 2023 in Obstetrics and Gynecology. Headache was the most common side effect, experienced by about 9 percent of people taking fezolinetant, similar to the proportion of placebo participants with this symptom. But the prescribing information includes a warning for elevated liver transaminases or liver damage. Before using Veozah, people should have blood tests to check for liver damage. During treatment with Veozah, routine blood tests should be done every three months for the first nine months of use.
This study also looked at the potential for changes in endometrial tissue that could indicate an elevated risk of uterine cancer and reductions in bone density that could lead to an increased risk of fractures. There were no significant changes in endometrial tissue or bone health associated with the treatment.
Paroxetine has been associated with a rare increased risk of fractures, according to FDA safety information. This drug also has other rare side effects, including an increased risk of suicidal thoughts and bleeding.
For most under the age of 60, hormone therapy is safe and effective for hot flashes if they take these drugs within the first 10 years of menopause, says Makeba Williams, MD, associate professor and director of midlife medicine and menopause at Washington University in Washington. St. Louis School of Medicine.
The fear of hormone therapy persists
Many women have been reluctant to use hormones for menopausal symptoms since 2002, when the Women’s Health Initiative (WHI) study linked treatments containing a certain type of estrogen and progestin to an increased risk of heart attacks, strokes and breast cancer . Even though subsequent analyzes and studies have found that the benefits of hormones far outweigh the risks for most women, the WHI findings continue to make many women fear hormones, says Dr. Williams.
Today, hormone therapy remains the most effective option for hot flashes, according to NAMS. Women over 60 may want to avoid hormones due to an increased risk of heart attack and stroke, and people with a history of breast cancer are also advised against using menopause hormones. But most women can use these medicines for symptoms like hot flashes that develop within the first decade after menopause, NAMS advises.
However, due in part to persistent safety concerns raised by the WHI study, three out of four women who experience hot flashes and other menopausal symptoms are not receiving treatment, according to an independent survey conducted in 2021.
For any woman concerned about the risks of hormones, fezolinetant could very well be the next alternative, Williams notes. I see fezolinetant becoming a first-line option for women with moderate to severe vasomotor symptoms who have a contraindication or aversion to hormone therapy, she says.
Additional reporting by Linda Thrasybule.
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