FDA-approved brain-based treatment for menopausal hot flashes

Hot flashes.

Fezolinetant offers a way to treat hot flashes without resorting to hormone therapy.Credit: SpeedKingsz/Shutterstock

U.S. regulators have approved a first-of-its-kind treatment that targets the neural pathways that cause hot flashes, a condition that affects more than 80% of menopausal women.

The U.S. Food and Drug Administration’s (FDA) approval on May 12 for fesolinetant (Veozah) provides a way to treat hot flashes without resorting to hormone therapy. “A lot of us in women’s health are really excited,” says Joanne Pinkerton, a gynecologist at the University of Virginia Health System in Charlottesville. “It’s very rare to see a breakthrough change in women’s health.” I recognize that not everyone who self-identifies goes through menopause, and not everyone who goes through menopause is female.)

The transition to menopause is a natural process that usually occurs between the ages of 45 and 55, culminating in decreased estrogen production and cessation of menstruation.

This transition can lead to complex symptoms of varying intensity and duration, including fatigue, anxiety, headaches and hot flashes. Hot flashes are the most common symptom, which feels like a sudden wave of heat that hits the upper body, causing women to feel hot, hot, and sweaty. Some people may also experience dizziness or heart palpitations.

Hot flashes during the day can interfere with work, sex, exercise, and socializing. Nocturnal hot flashes can cause sleep disturbances and over time can adversely affect a woman’s health. “Hot flashes are more than just nuisances,” says Pinkerton. “This has a significant impact on women’s lives.”

US researchers found that black women tend to have more frequent and severe hot flashes than white women.1.

Treatment without hormones

For decades, hormone replacement therapy has been the most effective treatment for hot flashes. It replaces estrogen and possibly other hormones that are naturally under-produced. But for many women, especially those with a history of stroke, migraines, or certain breast cancers, this is not an option.

In the 1990s, Naomi Lance, a neuropathologist at the University of Arizona in Tucson, found a larger group of brain cells in the brains of postmenopausal women than in premenopausal women. Dr. Lance further added that these cells, called KNDy neurons, respond to a molecule called neurokinin B, and when you block the receptors that allow these neurons to recognize neurokinin B, symptoms mimic hot flashes in rats. I found that it can be blocked.

Subsequent clinical studies found similar pathways at work in women’s brains. Fezolinetant, made by Tokyo-based Astellas Pharma Inc., works by blocking a protein called the neurokinin-3 receptor that mediates the heat dissipation response to neurokinin B.

Clinical trials of fesolinetant have shown that it can significantly reduce the frequency of hot flashes by approximately 60% in women experiencing moderate or severe hot flashes each week, compared to a 45% reduction in women who receive a placebo. was shown.2. Participants also reported that the drug reduced the severity of hot flashes and improved sleep quality.

However, for most women, fesolinetant does not completely eliminate hot flushes. Dr. Pinkerton is testing similar drugs that block receptors for both neurokinin-3 and related molecules called neurokinin-1. This may also improve mood and sleep quality.

Other connections

At the University of California, Los Angeles, neuroendocrinologist Stephanie Correa is studying how body temperature is regulated in rodents in hopes of devising additional treatments. “Body temperature is regulated by circuits in the brain that have many connections,” she says. “And Fezorinetant really focuses on her one of those connections.”

But much of the research on the basic biology of thermoregulation has historically been done in male rodents, she notes, making it difficult to trace these connections. How these results are reflected in people, especially women, is still an open question.

In the meantime, even partial relief of hot flashes is a big step forward, Correa said. Marcy English, vice president of biopharmaceutical development at Astellas Pharma, said some of the pivotal clinical trials of fesolinetant were conducted at the height of the COVID-19 pandemic. The company initially believed that trial researchers, like many others, would struggle to enroll participants at a time when many people were staying at home and shunning the medical field. .

However, the demand for potential therapeutics remained high. “Researchers in the field have told us, ‘No, you don’t get it.’ Everyone still wants to participate in this study,” says English. “It was amazing.”

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