More than 50% of OB/GYNs don't know these facts about the latest nonhormonal VMS drug—do you?
Industry Buzz
“Just this year, we have an entire, new class of medications available to women—neurokinin antagonists. [These are] a game changer for those women who cannot or choose not to take hormones. This class of medications directly targets the body’s thermostat and, as such, treats vasomotor symptoms at the core.” — Christine Palmay, MD, family medicine physician
We finally have an FDA-approved nonhormonal drug to treat some of the worst symptoms of menopause—so why are the majority of today’s OB/GYNs in the dark about it?
MDLinx asked some basic clinical questions about fezolinetant (Veozah), and the results revealed some significant knowledge gaps—would you have been able to get them right?
We asked docs, “What is the FDA-approved dosage of fezolinetant to treat vasomotor symptoms (VMS) in menopausal women?” and 47% got it wrong. Then, we asked, “A woman being treated for VMS with fezolinetant should undergo liver enzyme monitoring at which intervals? And 67% didn’t know the answer.
These findings raise concerns about real-world understanding of a first-in-class drug many clinicians are prescribing.
Symptom relief, hormone-free
Approved by the US FDA in 2023 (shortly followed by approval in the EU),[] fezolinetant is a nonhormonal treatment for moderate to severe VMS (eg, hot flashes, night sweats) associated with menopause. Unlike traditional hormone therapy, fezolinetant selectively blocks neurokinin 3 (NK3) receptors in the hypothalamus, helping to stabilize the body’s thermoregulatory center.[]
“Just this year, we have an entire, new class of medications available to women—neurokinin antagonists,” says Christine Palmay, MD, a family medicine physician in Canada. “This class of medications is nonhormonal and indicated to treat moderate to severe vasomotor symptoms in menopausal women, and it’s a game changer for those women who cannot or choose not to take hormones. This class of medications directly targets the body’s thermostat and, as such, treats vasomotor symptoms at the core.”
This mechanism makes fezolinetant particularly useful for patients with contraindications to estrogen, including those with a history of hormone-sensitive cancers, thromboembolic events, or cardiovascular disease.[]
Diving in to the data
The efficacy and safety of fezolinetant have been rigorously evaluated across a series of pivotal Phase 3 clinical trials, collectively known as the BRIGHT SKY™ program, which includes SKYLIGHT 1, SKYLIGHT 2, and SKYLIGHT 4, as well as Moonlight 1 and Moonlight 3. These studies enrolled women aged 40-65 with a body mass index no higher than 38 kg/m², and who experienced a minimum average of 7-8 moderate to severe hot flashes per day, or 50-60 per week.[][][][]
In the 12-week randomized controlled trials, SKYLIGHT 1 and SKYLIGHT 2, the 45-mg once-daily dose of fezolinetant consistently demonstrated a significant reduction in both the frequency and severity of VMS compared to placebo. While the reduction in VMS frequency did not always meet the minimum clinically important difference (MCID) of >3.57 hot flashes daily, the reduction in VMS severity did exceed the MCID (>0.225 hot flashes daily) in SKYLIGHT 2.[5] Beneficial effects on VMS were sustained in 52-week follow-up extensions, indicating long-term efficacy.[]
Beyond objective measures, fezolinetant also showed significant improvements in patient-reported outcomes. Pooled data from the SKYLIGHT trials showed significant improvements in scores on the Menopause Quality of Life Questionnaire (MENQoL).[]
Additional research highlights positive impacts on sleep quality and work productivity—crucial aspects of daily life often disrupted by VMS. These improvements underscore the drug's ability to enhance overall quality of life for menopausal women.[]
A meta‑analysis of five studies totaling ~3,300 participants confirmed significant reductions in VMS and an acceptable safety profile.[]
Although the drug is often well-tolerated, a rare risk of serious liver injury prompted the FDA to add a Boxed Warning to the prescribing information in September 2024.[]
As Dr. Palmay notes, Canada also observes obligatory liver function tests (LFTs) with fezolinetant. “Veozah requires regular liver monitoring due to vigorous guidelines put forth by Health Canada. We have parameters in terms of liver enzyme testing that dictate when to avoid starting and/or stopping this medication. Any decision to start menopause therapy requires a conversation regarding personal risks and benefits—there is not a one-size-fits-all option,” she says.
Liver monitoring: When and why
MDLinx research shows a large gap in clinicians’ knowledge about liver monitoring with fezolinetant. This isn’t a minor detail—given fezolinetant’s Boxed Warning for hepatotoxicity, it’s imperative clinicians follow a strict liver monitoring schedule.[][]
Baseline liver enzymes (ALT, AST, bilirubin) must be obtained prior to initiation, followed by:
Monthly LFTs for the first 3 months
LFTs at 6 and 9 months
If ALT or AST exceeds 3× ULN, therapy should be re-evaluated or discontinued.
In the clinic
“Nonhormonal drugs including an NK3 antagonist such as fezolinetant, antidepressants, oxybutynin, or gabapentin are effective for VMS. The choice depends on patient preference, risk profile, and comorbidities,” according to OB/GYN Alyssa Dweck, MD.
As an oral, once-daily pill, fezolinetant is often an easier and more convenient option for patients—especially for those who cannot, or prefer not to, take estrogen-based therapies. And for patients experiencing new risk factors, some doctors also consider it as a step-down therapy in those previously on systemic hormone therapy.
Related: Many physicians still consider VMS to be transient and inconsequential, but new research suggests otherwise—are you all caught up?