Fezolinetant counseling: Framing sleep benefit beyond hot flashes

Real-world sleep data on fezolinetant (Veozah) gave ob-gyns an additional, evidence-based point to raise when counseling patients with vasomotor symptoms who were hesitant about hormone therapy, according to Marla Shapiro, CM, MDCM, CCFP, MHSc, FRCPC, FCFP, MSCP. Shapiro preferred to describe the drug class by its mechanism—neurokinin 3 receptor antagonists—rather than as “nonhormonal” therapy, because the site of action in the brain is well understood.

Neither menopausal hormone therapy nor neurokinin 3 receptor antagonists carried a sleep indication; both were indicated for the management of hot flashes and night sweats. Sleep disturbance, however, was common and often not discussed in perimenopausal women, many of whom entered menopause with a sleep comorbidity that had not been diagnosed or addressed. Whether sleep improved simply because hot flashes improved remained an open question, Shapiro said, noting that menopausal hormone therapy studies had shown that reducing hot flashes did not necessarily improve sleep. Against that backdrop, the sleep benefit observed in real-world data—captured by patient-reported questionnaires as well as actigraphy measuring the individual components of sleep—was a notable finding.¹

The finding aligned with what patients described in the clinic.

“Often what drives them in is the hot flashes and night sweats, but they all talk about sleep and next-day exhaustion and not feeling that they’ve had restorative sleep,” Shapiro said.

When asked to name their single most important treatment goal, most women identified the severity and frequency of hot flashes and night sweats, which remained the target of therapy. Improved sleep—seen as early as week 4 and maintained at weeks 8 and 12—was framed as an added benefit most patients would value.¹ More women than men experienced sleep difficulty across the life span, and perimenopausal women were particularly affected. Shapiro could tell patients that randomized clinical trial data supported the safety and efficacy of fezolinetant for vasomotor symptoms, with efficacy as early as week 1, and that subjective and objective data now showed sleep improvements by week 4. That combination supported informed decision-making about treatment options.

Real-world evidence also addressed a limitation common to all clinical trials, regardless of therapeutic area: enrolled participants may not represent the patients clinicians see in practice. Although the pivotal SKYLIGHT trial populations were ethnically diverse, included women with normal body mass index and women with obesity, and allowed subanalyses across these groups, the central question was whether trial results translated to the woman sitting across the desk. Accumulating real-world and long-term safety data reinforced the trial findings and enabled ongoing safety monitoring of the medication.

“Studies have a beginning and they have an end and they have end points, but real-world evidence just keeps rolling forward,” Shapiro said. Real-world evidence that validated trial results was reassuring for both the prescriber and the patient, she added.

Reference

1. Shapiro M, et al. Fezolinetant and real-world sleep outcomes in the phase 4 OPTION-VMS study: second preliminary analysis of patient-reported and actigraphy-derived endpoints. Presented at: International Menopause Society 20th World Congress on Menopause. September 30-October 3, 2026. Accessed October 19, 2026