Could a new non-hormonal treatment reduce menopause’s hot flashes?

By Claire Wolters | Fact-checked by Davi Sherman
Published May 15, 2023

Key Takeaways

  • Hormonal estrogen treatments may relieve vasomotor symptoms in menopause.

  • But not everyone with menopause can tolerate hormonal treatments.

  • Now, some companies are seeking FDA approval for non-hormonal VMS treatments.

People who go through menopause may benefit from hormonal treatments that replenish lost estrogen and regulate body temperature. But not all people can tolerate hormonal treatments, and some face barriers to accessing quality care.

Decreases in estrogen levels and increases in the brain’s Neurokinin B receptor are believed to be the primary drivers of menopause’s vasomotor symptoms (VMS), including hot flashes and night sweats. As people’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,” explains Rahman.

Kisspeptin, neurokinin B, and dynorphin (KNDy) are neurons in the brain’s hypothalamus that work with hormones like estrogen. 

Many of 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, or 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), she adds. 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 says.

Now, some companies are seeking Food and Drug Administration (FDA) approval to give these patients a new, non-hormonal option. And some studies suggest it could 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 neurokin B receptor, estrogen’s copilot when it comes to aggravating VMS symptoms.

One drug being studied (and recently received FDA-approval) is Fezolinetant, a neurokinin 3 receptor (NK3R) antagonist that works to reduce NKB levels and alleviate VMS symptoms.[] (The NKB receptor primarily works through the NK3R receptor.) A double-blind, placebo-controlled study on menopausal women in multiple countries between July 2019 and August 2021 found fezolinentant to significantly reduce VMS symptoms and their frequency. Other studies have found that “NK3R antagonism rapidly relieves vasomotor symptoms without the need for estrogen exposure.”[][]

If approved, this therapy could be 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 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. I can only hope that insurance will cover this med, or it is not cost-prohibitive for patients who need it.”

What this means for you

Some people take hormonal estrogen treatments to relieve menopause’s vasomotor symptoms. But people who cannot take estrogen due to health conditions have to alleviate their symptoms with lifestyle changes. Now, new non-hormonal therapies are seeking FDA approval.

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