Evaluating Newer Non-Hormonal Therapies for VMS

In "Evaluating Newer Non-Hormonal Therapies for VMS," our panel explores the similarities and distinctions between fezolinetant and elinzanetant as NK receptor antagonists, with a focus on how these differences inform clinical decision-making for a patient with inadequate response to MHT. The experts begin by establishing that both agents share NK3 receptor antagonism as their primary mechanism, producing meaningful reductions in VMS frequency and severity. However, elinzanetant's additional NK1 receptor antagonism — and its resulting effect on substance P — sets it apart by delivering superior sleep outcomes, a distinction the experts describe as clinically palpable for patients rather than merely statistical.

The discussion turns to the key clinical trials supporting each agent — the SKYLIGHT 1 study for fezolinetant and the OASIS 1 and 2 studies for elinzanetant — noting that both were randomized, placebo-controlled trials. Both medications demonstrated early onset of efficacy, with patients noticing symptom improvements as soon as one week into treatment, and both showed continued improvement in VMS frequency and severity through twelve weeks.

The experts then address the safety profiles of the two agents, noting that fezolinetant carries a higher risk of liver enzyme elevations, prompting monitoring requirements at baseline and six additional timepoints over the first nine months of treatment — a burden for both patients and clinicians. Elinzanetant demonstrated lower rates of liver enzyme elevations in clinical trials, translating to a more streamlined monitoring schedule. The panel concludes by underscoring the particular importance of sleep improvement for this patient, emphasizing that better sleep has meaningful downstream effects on cognition, word finding, focus, and overall quality of life.

Our next episode, "Emerging Evidence on NK Receptor Antagonism and Bone Health in VMS," features two menopause experts examining the current and evolving evidence on elinzanetant's effects on bone density, body composition, and metabolic parameters, and discussing how these findings factor into treatment selection for a patient with mild osteopenia.