Genevieve Neal-Perry, MD, PhD, discusses new nonhormonal treatments for hot flashes

The treatment landscape for menopausal vasomotor symptoms has expanded dramatically in recent years, driven by the introduction of a new class of nonhormonal therapies that directly target the brain pathways responsible for hot flashes. According to Genevieve Neal-Perry, MD, PhD, Department Chair of Obstetrics and Gynecology at UNC School of Medicine, this represents one of the most significant advances in decades, offering more precise and effective options beyond traditional hormone therapy.

Historically, estrogen-based hormone therapy has been the most effective treatment for hot flashes, but it is not suitable for all patients. Women with a history of hormonally sensitive cancers, elevated risk of blood clots, or other contraindications often have limited safe options. The approval of neurokinin receptor antagonists has changed this reality by providing therapies that specifically act on the hypothalamic neurons involved in thermoregulation, rather than broadly affecting multiple body systems.

Fezolinetant, approved in 2023, was the first medication in this class and has demonstrated strong efficacy in reducing hot flashes and improving quality of life. More recently, elinzanetant, which targets both neurokinin-1 and neurokinin-3 receptors, has become available as another nonhormonal option. Both drugs are highly effective, but they differ in their side effect profiles and practical considerations. Elinzanetant may be preferable for women who experience significant sleep problems, as it tends to be more sedating, whereas fezolinetant is less likely to cause drowsiness.

Both medications have been associated with potential liver enzyme elevations, and monitoring is required, though current protocols may differ in duration between the 2 agents. Coverage and access also vary, with fezolinetant more widely included on insurance formularies because of its earlier approval.

Looking ahead, important unanswered questions remain. Severe, untreated hot flashes have been linked to greater risks of cardiovascular disease, inflammation, and cognitive decline, including dementia. Researchers are now working to determine whether treating vasomotor symptoms with neurokinin receptor antagonists can modify these long-term risks in ways similar to, or distinct from, estrogen therapy. These therapies may be especially valuable for breast cancer survivors, a population that often cannot use hormonal treatments, though more data are needed to guide optimal, coordinated care.

Finally, real-world evidence is emerging to complement clinical trial data. Early findings presented at professional meetings suggest fezolinetant may be more effective than selective serotonin reuptake inhibitors for hot flash management, with reassuring safety data and minimal liver concerns in practice. Ongoing real-world studies are expected to further refine how these medications can be used to deliver more personalized, effective symptom relief.

No relevant discosures.