VMS and Menopause: KNDy Neurons, NK Receptors, and Practical Insights

Panelists discuss how KNDy neurons, which coexpress kisspeptin, neurokinin B (NKB), and dynorphin genes, play a crucial role in hormonal reproduction and the development of vasomotor symptoms (VMS) in menopause.

Panelists discuss how neurokinin 3 (NK3) receptors contribute to vasomotor symptoms (VMS) and how antagonism of NK3 receptors with drugs like fezolinetant can effectively reduce VMS, while also exploring the dual receptor action of elinzanetant, which blocks both NK1 and NK3 receptors to improve VMS and associated sleep disturbances.

Panelists discuss how to simplify the physiology of KNDy neurons and neurokinin (NK) receptors for primary care physicians, explaining how NK3 antagonism reduces hot flashes, while NK1 antagonism helps alleviate sleep disturbances and night sweats, with fezolinetant and elinzanetant serving as key nonhormonal treatment options.

Panelists discuss why a warning about serious liver injury was added to the prescribing information for fezolinetant following a postmarketing case of drug-induced liver injury, and review updated guidelines for baseline liver testing, recommended monitoring, symptoms indicating the need to discontinue the medication, and key points for addressing patient concerns about liver health.

Panelists discuss why elinzanetant is likely to be associated with a lower risk of liver injury due to its distinct molecular structure compared to fezolinetant, and compare the adverse event profiles of the 2 drugs, highlighting that elinzanetant is more commonly associated with headache and fatigue while fezolinetant is linked to abdominal pain, diarrhea, insomnia, and back pain.

Panelists discuss clinical trial data suggesting a small but higher incidence of endometrial hyperplasia or malignancy with fezolinetant, while no cases of endometrial hyperplasia or malignancy were observed with elinzanetant in a long-term safety study.

Panelists discuss key considerations for women taking hormonal therapy, emphasizing the importance of individualized treatment plans and shared decision-making to evaluate the risk-benefit profile of therapy.

Panelists discuss alternative therapies for women who are not candidates for or choose not to use hormonal therapy, review nonhormonal treatment options recommended by the North American Menopause Society, and explore the growing importance of Level I evidence and consensus opinions in creating a more holistic view of available therapies, both hormonal and nonhormonal.

Panelists discuss strategies for simplifying complex information for primary care physicians (PCPs), provide tips on how PCPs can effectively communicate evidence-based treatment options to patients, and outline actionable points and key takeaways to enhance patient care in managing menopause symptoms.