Could a new non-hormonal treatment reduce menopause’s hot flashes?
Key Takeaways
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“When you hit menopause, your estrogen levels decline, and this causes your NKB signaling pathways to increase, and this causes a potential upregulation of the KNDy neurons [Kisspeptin, neurokinin B, and dynorphin] and thermal dysregulation.” — Sameena Rahman, MD, board-certified OB/GYN
People who go through menopause may benefit from hormonal treatments that replenish lost estrogen and regulate body temperature. But not everyone can tolerate hormonal treatments, and some face barriers to accessing quality care.
Estrogen drops, NKB rises—and the brain heats up
Decreases in estrogen levels and increases in the brain’s Neurokinin B (NKB) receptor are believed to be the primary drivers of menopause’s vasomotor symptoms (VMS), including hot flashes and night sweats. As patient’s estrogen levels decrease, these symptoms can become “vast and relentless,” says Sameena Rahman, MD, a board-certified OB/GYN at the Center for Gynecology and Cosmetics in Chicago.
“When you hit menopause, your estrogen levels decline, and this causes your NKB signaling pathways to increase, and this causes a potential upregulation of the KNDy neurons [Kisspeptin, neurokinin B, and dynorphin] and thermal dysregulation,” Dr. Rahman tells MDLinx.
Kisspeptin, neurokinin B, and dynorphin (KNDy) are neurons in the brain’s hypothalamus that work with hormones like estrogen.
When hormones aren’t an option...
Many of Dr. Rahman’s patients benefit from hormonal treatments, which are the “gold standard of care,” she says. But others—in particular, patients who have conditions like active or advanced breast cancer, undiagnosed uterine or vaginal bleeding, liver disease, or histories of heart attacks or unprovoked blood clots in their legs or lungs—cannot or may not be able to take them, she says.
Instead, these patients often must manage symptoms through lifestyle alterations or behavioral modifications, like regulating indoor temperatures at home or work, using portable fans, and wearing layered clothing (to take on and off as needed), according to Dr. Rahman. Some people may also benefit from losing weight; undergoing therapies like cognitive behavioral therapy or hypnosis; or taking supplements, like vitamin E, or prescribed SSRI/SNRI antidepressants or anti-seizure medications, she adds.
Luckily, there’s an FDA-approved option that gives these patients a new, non-hormonal option. And it may work just as well, if not better, than the hormonal therapies currently on the table.[]
How does a non-hormonal VMS treatment work?
Non-hormonal VMS treatment works by targeting the brain’s NKB receptor, estrogen’s copilot when it comes to aggravating VMS symptoms.
Fezolinetant, a neurokinin 3 receptor (NK3R) antagonist that works to reduce NKB levels and alleviate VMS symptoms, received FDA approval in 2023.[] (The NKB receptor primarily works through the NK3R receptor.)
A double-blind, placebo-controlled study on menopausal women found that fezolinetant significantly reduced VMS symptoms and their frequency. Other studies have found that “NK3R antagonism rapidly relieves vasomotor symptoms without the need for estrogen exposure.”[][]
In a more recent January 2025 meta-analysis of five randomized controlled trials that included 3,295 postmenopausal women, researchers found fezolinetant reduced hot flash frequency and severity, while improving sleep and quality of life. Fezolinetant at either 30 mg or 45 mg once daily is both effective and generally well tolerated.[]
This therapy is the first non-hormonal treatment for menopause VMS symptoms, filling a gap for those who have been relying on behavioral modifications.[]
“There is not a one size fits all equation for treating VMS,” says Dr. Rahman. “It is exciting to see a new potential for medications for women, and that research is expanding for women in the midlife who are often the forgotten patient base.”