The Next Evolution of Non-Hormonal Menopause Care: Fezolinetant

Hot flashes and night sweats, otherwise known as vasomotor symptoms, are among the most common symptoms of menopause. For some, they are occasional and mild. For others, they may disrupt sleep, interfere with work or exercise, affect mood and cognition, and overall, can reduce one’s quality of life.

The significant impact vasomotor symptoms can have on one’s daily life has driven efforts to better understand why they occur and to develop more effective treatment options. As researchers learned more about how hot flashes develop in the brain, they were able to develop other medications, like fezolinetant (brand name, Veozah), a medication that targets a physiologic process in the brain involved in vasomotor symptoms.

Why Was a New Treatment Needed?

Hormone replacement therapy (HRT) remains the most effective treatment for vasomotor symptoms. However, some cannot use HRT because of their medical history, while others prefer to avoid it due to side effects or concerns about risks.

For decades, the non-hormonal options available to non-hormone users were herbal remedies and medications originally developed for other conditions, such as depression, seizure disorders, hypertension, or overactive bladder. Although these medications can reduce hot flashes for some, none were designed specifically to treat menopausal vasomotor symptoms, and could cause adverse effects such as drowsiness, fatigue, dizziness or difficulty with concentration.

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At the same time, researchers were learning more about the brain pathways and neurochemicals involved in hot flashes. The discovery of the neurokinin B signaling pathway and mechanism behind vasomotor symptoms in the thermoregulatory area of the brain led to the development of a new medication that targeted the underlying receptors and neurochemicals involved in vasomotor symptoms.

Fezolinetant was the first in its class of neurokinin 3 receptor antagonists, and was developed to fill this therapeutic gap in the non-hormonal treatment of vasomotor symptoms. 

How Fezolinetant Works

The hypothalamus contains a group of nerve cells called KNDy neurons that help regulate body temperature. During the reproductive years, estrogen helps keep this system functioning in balance and the core body temperature within a normal range. As estrogen levels decline during menopause transition, signaling by a neurochemical messenger called neurokinin B (NKB) increases, making these neurons more active.

This increased activity narrows the body's normal temperature regulation range, causing even small changes in body temperature to trigger heat-loss responses such as hot flashes and sweating.

Fezolinetant works by blocking a receptor called neurokinin 3 (NK3), which prevents NKB from activating this pathway. This reduces overstimulation of the KNDy neurons and helps stabilize the body's temperature regulation, reducing the quantity and intensity of hot flashes.

“Patients who use fezolinetant typically report a very quick reduction in those vasomotor symptoms, within days to weeks, and very similar to hormone therapy which makes it a nice alternative option for those who cannot or can no longer use hormone therapy.” Dr Traci Kurtzer 

What Studies Show

Clinical trials of fezolinetant showed that it reduced both the frequency and severity of moderate to severe hot flashes. Many on the medication experienced improvement within the first few weeks of treatment and continued to show progress over time. Symptom improvement was sustained over the full year of monitoring.

Recent real-world studies suggest these changes extend beyond controlled clinical trial settings. Users of fezolinetant also reported better sleep, likely from reduced night sweats and restlessness from just feeling warm.

Beyond Hot Flash Relief

Hot flashes and night sweats can affect many aspects of daily life beyond the episodes themselves. Frequent symptoms, particularly those that disrupt sleep, have been associated with fatigue, difficulty concentrating, reduced productivity, and higher rates of anxiety and depressive symptoms. Alone or combined, these effects can have an impact on quality of life during menopause.

In addition to reducing hot flashes and night sweats, recent real-world studies found that those taking fezolinetant reported lower anxiety and depressed mood, with changes observed as early as four weeks after starting treatment.

Because fezolinetant does not affect serotonin or other neurotransmitters typically targeted by antidepressants, researchers believe these changes are more likely related to reducing the physical burden of vasomotor symptoms, improving sleep, and allowing users to function more comfortably and effectively during the day.

Safety and Practical Considerations

Like every prescription medication, fezolinetant offers potential benefits as well as important safety considerations.

Before starting fezolinetant, a baseline set of normal liver function tests is required and there is ongoing monitoring, monthly to start and then quarterly, during the first year of treatment because rare cases of serious liver injury have been reported. For those who are appropriate candidates, these monitoring recommendations are intended to help clinicians identify uncommon problems early while allowing treatment to continue safely for the vast majority.

However, the medication is not appropriate for everyone and should not be used with certain medications or with some baseline liver and kidney conditions. Although most do very well with use, potential side effects can include abdominal pain, flushing, nausea, and elevated liver enzymes. All those with liver enzyme abnormalities had resolution to normal levels with drug discontinuation and no long term adverse effects. 

A Safe and Effective Alternative to HRT

The development of fezolinetant illustrates how advances in understanding the biology and physiology of menopause can lead to new treatment options. By targeting one of the main pathways involved in hot flashes and night sweats, patients and clinicians now have an effective primary, nonhormonal approach rather than having to use medications really intended for other conditions. As research continues to expand our understanding of menopause and the science behind the symptoms, additional targeted therapies will become available and further broaden treatment options for menopausal symptoms. It’s an exciting time in menopause care and we are happy to be here to help our patients navigate these complex decisions and regain their quality of life!

“I really love helping out my colleagues and those patients with complex medical histories that make menopause care more challenging. I will always try to think outside of the box to get as many as possible on hormones, given the other preventative health and quality of life benefits from hormone therapy. However, we do have a lot of options, some old and some new, to help those who cannot use hormone replacement therapy… So, you should never feel you just have no choice but to suffer.” - Dr Traci Kurtzer

*Disclosure: Dr Kurtzer was a former member of the physician Advisory Board and the Speaker’s Bureau on behalf of Veozah (fezolinetant) for Astellas Pharma Inc. 

Frequently Asked Questions

How does fezolinetant work to reduce hot flashes?

Fezolinetant targets the hypothalamus, the area of the brain that regulates body temperature. As estrogen levels decline during menopause, a neurochemical messenger called neurokinin B (NKB) increases and overstimulates a group of nerve cells called KNDy neurons, narrowing the body's normal temperature range. Fezolinetant works by blocking the neurokinin 3 (NK3) receptor, preventing NKB from activating this pathway. This stabilizes the body's temperature regulation and quickly reduces the number and intensity of hot flashes.

Why was fezolinetant developed as a new non-hormonal alternative?

For decades, the only non-hormonal options available for managing menopausal symptoms were herbal remedies or medications originally designed for other conditions, such as depression, seizures, or hypertension. These older medications were not specifically designed for menopause and often caused adverse effects like drowsiness, dizziness, and difficulty concentrating. Fezolinetant was developed as the first in its class to fill this therapeutic gap by directly targeting the specific brain pathway responsible for vasomotor symptoms.

What safety monitoring is required when taking fezolinetant?

Because rare cases of serious liver injury have been reported, patients are required to get a baseline set of normal liver function tests before starting fezolinetant. Ongoing liver monitoring is also required throughout the first year of treatment, occurring monthly at the start and moving to a quarterly schedule later on, to help clinicians identify any uncommon problems early.

References

The 2023 Nonhormone Therapy Position Statement of The Menopause Society Advisory Panel. Menopause. 2023;30(6):573-590. doi:10.1097/GME.0000000000002200.

Gatson AL, Jenkins JL, Hornsby LB, Phillippe HM. Fezolinetant: a novel nonhormonal therapy for vasomotor symptoms due to menopause. Expert Opin Pharmacother. 2024;25(10):1145-1153. doi:10.1080/14656566.2024.2363967.

Mueck AO, Genazzani AR, Regidor PA. Targeting vasomotor symptoms with the new drug fezolinetant: an expert overview. Gynecol Endocrinol. 2025;41(1):2526560.

Neal-Perry G, Ottery FD, Lederman S, et al. Early onset, maintenance of effect, and day-/night-time findings following fezolinetant treatment for moderate to severe vasomotor symptoms associated with menopause: a pooled phase 3 analysis. Maturitas. 2025;194:108740.

Wang X, Liu Y, Zhang H. Efficacy and safety of fezolinetant and elinzanetant for vasomotor symptoms in postmenopausal women: a systematic review and meta-analysis. J Affect Disord. 2025;372:112-121.

Becker KA, et al. Long-term safety and tolerability of fezolinetant for vasomotor symptoms: results from a 52-week phase 3 study. J Clin Endocrinol Metab. 2024;109(6):e215-e224.

Maki PM, et al. Non-hormone medication addresses menopausal symptoms in women: the OPTION-VMS study. Presented at: ENDO 2026; Endocrine Society Annual Meeting; July 2026.

Santoro N, Waldbaum A, Nappi RE, et al. Fezolinetant effect on vasomotor symptoms due to menopause in women unsuitable for hormone therapy. Menopause. 2024;31(4):285-294.