Managing Vasomotor Symptoms With NK3 Receptor Antagonism

Fezolinetant, an NK3 receptor antagonist approved in 2023, represents a milestone in nonhormonal menopause therapy. The panel discusses how it acts by modulating KNDy neuron activity in the hypothalamus, stabilizing thermoregulation, and reducing hot flash frequency and severity.

Clinical trial data, particularly from the phase 3 SKYLIGHT studies, demonstrated significant reductions in vasomotor symptoms (VMS) within weeks of treatment initiation. Safety profiles were favorable, with mild to moderate adverse events and minimal liver concerns compared with earlier therapies.

This approach marks a paradigm shift by targeting central neural pathways rather than peripheral hormones, expanding therapeutic options for diverse patient populations seeking safer alternatives.