NK3 as a Drug Target: From Scientific Discovery to Guideline-Recognized Therapy

This episode, titled 'NK3 as a Drug Target: From Scientific Discovery to Guideline-Recognized Therapy,' features panelists discussing the following critical questions:

1. How did the identification of the KNDy neuron system lead researchers to the NK3 receptor as a target? What made it a compelling focus for drug development?
2. What does this mechanism mean for patients who cannot or will not take hormone therapy?
3. How have the guidelines around menopause and hormone therapy evolved since the addition of KNDy receptor antagonists?

Led by the moderator, the panelists examined how the discovery of the KNDy neuron system represented a watershed moment in VMS research, shifting the field's understanding beyond simple estrogen deficiency and opening a mechanistically grounded, non-hormonal drug development pathway for the first time. The discussion highlighted the profound clinical significance of this discovery for the large and underserved population of women who cannot or choose not to take hormone therapy, including breast cancer survivors, those on ovarian suppression, and women who have moved past the window of opportunity for estrogen initiation for whom NK3 receptor antagonists now offer a purpose-built, FDA-approved treatment option. The panelists also traced the rapid evolution of clinical guidelines to reflect this innovation, noting that fezolinetant earned a recommendation from The Menopause Society's 2023 non-hormone therapy position statement, and that the International Menopause Society's 2025 guidelines go further by designating neurokinin antagonists as the preferred non-hormonal treatment for VMS.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

In the next episode, 'Two New Tools for VMS: A Clinical and Pharmacological Comparison of NK Receptor Antagonists,' panelists will continue their discussion on vasomotor symptoms and menopause and highlight the key similarities and differences between fezolinetant and elinzanetant, including their mechanisms of action, half-life data, drug interaction profiles, liver function monitoring requirements, and practical clinical considerations for patient counseling and treatment selection.