Detailed definition
Fezolinetant is the first FDA-approved neurokinin-3 receptor antagonist for vasomotor symptoms. The drug was approved in May 2023 based on the SKYLIGHT trials, which showed significant reductions in moderate-to-severe hot flash frequency and severity vs. placebo by 4 and 12 weeks. The mechanism: estrogen normally restrains the activity of KNDy (kisspeptin/neurokinin B/dynorphin) neurons in the hypothalamic arcuate nucleus that influence the thermoregulatory center. Estrogen withdrawal leads to KNDy neuron hypertrophy and excessive neurokinin B signaling, dysregulating the thermoneutral zone. NK3 receptor antagonism rebalances this circuit without altering estrogen levels. Standard dosing is 45 mg orally once daily. The FDA initially required liver function monitoring at baseline and during the first 9 months because of hepatotoxicity signals; updated labeling reflects monitoring requirements. Fezolinetant does not treat GSM, mood, or bone — it is specifically a vasomotor-symptom drug.
Why it matters in menopause
Fezolinetant is the first non-hormonal hot flash drug that targets the underlying mechanism rather than working downstream (like SSRIs or gabapentin). For breast cancer survivors and other women who cannot use estrogen, it is a meaningful new option. The trade-off is liver-function monitoring and substantial cost relative to generic SSRIs.
Related terms
Sources
External references: Wikipedia.