Key takeaways:
- Fezolinetant (Veozah) and elinzanetant (Lynkuet) are both effective for VMS, but elinzanetant's additional NK1 receptor antagonism—which modulates substance P signaling—may offer more targeted benefit for sleep disruption beyond hot flash suppression.
- Approximately one quarter of women presenting to the Menopause and Women's Sexual Health Clinic with midlife sleep disturbance were found to be at intermediate or high risk for obstructive sleep apnea, underscoring the importance of screening before attributing sleep symptoms to VMS alone.
- With an estimated half of postmenopausal women affected by some form of sleep disorder, systematic evaluation of the primary driver—VMS, insomnia, mood disorder, or obstructive sleep apnea—is essential to selecting the right treatment approach.
The arrival of 2 neurokinin receptor antagonists on the market has meaningfully expanded non-hormonal options for vasomotor symptom (VMS)-related sleep disruption—but effective management requires distinguishing between sleep disturbance that will respond to VMS treatment and sleep pathology that needs its own dedicated intervention, according to Stephanie S. Faubion, MD, MBA, FACP, MSCP, IF, director, Mayo Clinic Center for Women’s Health; professor and chair, Department of Medicine, Mayo Clinic, Jacksonville, Florida; and medical director, The Menopause Society. presented a talk titled "Is Quality Sleep in Menopause Just a Dream? Navigating Hot Flashes, Night Sweats, and Sleep Disturbances with Novel Non-Hormonal Therapies" at SLEEP 2026 with Shelby Harris, PsyD.
Faubion described the neurokinin receptor antagonist class as the most significant development in non-hormonal VMS management in recent years, tracing its origins to foundational research by Naomi Rance, MD, PhD, over the past decade and a half. Two agents are now available: fezolinetant (Veozah), approved in 2023, and elinzanetant (Lynkuet), approved in fall 2025. Both are effective for VMS relief and quality-of-life improvement, but their receptor profiles differ in a clinically relevant way. Fezolinetant targets the NK3 receptor, which is primarily involved in vasomotor symptom regulation. Elinzanetant targets both NK1 and NK3 receptors—and NK1 blockade, which modulates substance P signaling, may confer additional sleep-specific benefits beyond hot flash reduction.
"We think that elinzanetant may be a little more targeted to sleep specifically in addition to vasomotor symptoms," Faubion said.
For clinicians, however, selecting the right agent is only part of the challenge. Identifying what is actually driving the sleep disruption—VMS, primary insomnia, a mood disorder, or an undiagnosed sleep disorder—is a prerequisite for effective treatment.
"It's really important for the clinician to figure out what is contributing to what so that we're addressing the right things," Faubion said. "We might honestly treat insomnia in a different way than we would treat nighttime hot flashes."
Obstructive sleep apnea warrants particular attention. Data from the Menopause and Women's Sexual Health Clinic showed that approximately one quarter of patients presenting with midlife sleep disturbance and vasomotor symptoms were found to be at intermediate or high risk for obstructive sleep apnea, with a meaningful proportion going on to receive a formal diagnosis.
"I would err on the side of screening them because it's easy to screen and it's a bad thing to miss," Faubion said. The clinical presentation in women may differ from the classic male pattern: Loud snoring is often absent, whereas morning headaches, fatigue, and predominantly nocturnal rather than daytime sweating may be more prominent features.
Restless leg syndrome is another midlife-prevalent condition that can disrupt sleep and is frequently overlooked. In women experiencing heavy menstrual bleeding around the menopause transition, iron deficiency may be contributing—a reversible and easily addressable cause of worsening restless leg symptoms.
The overall burden of sleep dysfunction in this population is substantial. Approximately half of postmenopausal women are estimated to have some form of sleep disorder, making systematic screening essential rather than optional. For women with significant hot flashes who are appropriate candidates, hormone therapy remains a highly effective option—particularly for those under 60 or within 10 years of menopause onset—with benefits that may extend to both nocturnal hot flash suppression and insomnia symptoms independent of VMS.
