Pathophysiology of Vasomotor Symptoms in Menopause

This educational roundtable convenes leaders in women’s health to discuss the pathophysiology and quality-of-life impact of vasomotor symptoms (VMS), emphasizing their neuroendocrine basis and connections to thermoregulation and overall health. Pauline Maki, MD, opens the program by highlighting how estrogen withdrawal affects KNDy neurons in the hypothalamus, triggering dysregulated thermoregulation that manifests as hot flashes and night sweats. The discussion underscores that untreated VMS can lead not only to discomfort and sleep disruption but also to potential cardiovascular, cognitive, and bone consequences over time. Panelists share real-world observations on how these symptoms interfere with professional productivity, relationships, and psychological well-being.

The conversation then transitions to emerging nonhormonal treatments targeting the NK receptor pathway. The group analyzes fezolinetant, the first FDA-approved NK3 receptor antagonist for VMS, and reviews efficacy and safety results from the SKYLIGHT trials, which demonstrated rapid symptom improvement within weeks. Discussion expands to elinzanetant, a dual NK3/NK1 receptor antagonist currently under FDA review, with findings from the OASIS 1-4 trials suggesting additive benefits for mood and sleep regulation alongside hot flash relief. The experts also discuss the broader implications of NK receptor biology, noting its expression in multiple organ systems and potential future relevance for bone, bladder, and emotional health.

Finally, the panel explores clinical integration and safety monitoring as these therapies enter broader use. They share insights on patient selection, timing of treatment initiation, and strategies to manage mild hepatic effects. The conversation emphasizes practical decision-making for choosing between NK3-only and dual NK3/NK1 antagonists, as well as tailoring therapy to patient preferences and comorbidities. The series concludes with key takeaways on the importance of clinician awareness, proactive education, and multidisciplinary collaboration in adopting these novel therapies — marking a significant shift in the nonhormonal management of menopausal VMS.