How does Veozah (fezolinetant) work for perimenopause?

Veozah is the brand name for fezolinetant, a non-hormonal oral medication that received FDA approval in May 2023 for moderate to severe vasomotor symptoms (hot flashes and night sweats) caused by menopause. Fezolinetant represents a genuinely new pharmacological approach: rather than replacing declining hormones or broadly modulating neurotransmitter systems, it targets the specific neurological mechanism that produces hot flashes at its source in the hypothalamus.

To understand how fezolinetant works, it helps to understand the neurobiology of hot flashes in detail. Deep in the hypothalamus, a cluster of neurons called KNDy neurons (named for the three neuropeptides they co-release: kisspeptin, neurokinin B, and dynorphin) act as critical regulators of both reproductive hormones and body temperature. Neurokinin B (NKB) is the key peptide in this context: it is released by KNDy neurons and binds to NK3 receptors on neighboring neurons in the thermoregulatory center of the hypothalamus. This binding activates a cascade that triggers the peripheral vasomotor response, the sudden vasodilation and sweating of a hot flash.

In premenopausal women, estrogen suppresses KNDy neuron activity, keeping NKB release and NK3 receptor signaling at a controlled level. This estrogen-mediated suppression keeps the thermoregulatory system stable. When estrogen declines during perimenopause, KNDy neuron activity increases substantially and the suppression of NKB release is lost. The result is that NK3 receptors are repeatedly activated by NKB, firing the thermoregulatory cascade over and over, producing the frequent hot flashes and night sweats that characterize perimenopausal and postmenopausal experience.

Fezolinetant is a selective, competitive antagonist of the NK3 receptor. It binds to NK3 receptors and blocks NKB from activating them, directly interrupting the signaling pathway that triggers hot flashes. This is a mechanism-targeted approach: rather than correcting the upstream hormonal deficiency (as estrogen therapy does) or broadly modulating neurotransmitter systems (as SSRIs and SNRIs do), fezolinetant goes straight to the neural circuit that produces the symptom.

The clinical evidence supporting fezolinetant comes from the SKYLIGHT trial program, a series of well-designed randomized controlled trials. SKYLIGHT 1 and SKYLIGHT 2 were phase 3 trials showing that fezolinetant 45 mg once daily reduced hot flash frequency by approximately 58 to 63 percent and reduced hot flash severity significantly compared to placebo at 12 weeks, with sustained effects maintained through 52 weeks of treatment. The FDA approved the 45 mg dose; the 30 mg dose showed clinically meaningful but somewhat smaller effects. These are substantial reductions for a non-hormonal therapy, comparable in magnitude to what SNRIs and SSRIs achieve, though somewhat less than the 75 to 90 percent reductions seen with estrogen therapy.

Fezolinetant is hormone-free, which makes it a critically important option for women who cannot or choose not to use hormonal therapy: breast cancer survivors, women with elevated cardiovascular risk, women with clotting disorders, and women who simply prefer a non-hormonal approach. Because its mechanism is purely neurological rather than hormonal, it does not affect bone density, vaginal tissue, mood, or other domains that estrogen therapy addresses. Women with significant genitourinary symptoms, bone loss concerns, or mood-related perimenopausal symptoms will need separate management for those issues.

The most significant safety concern that emerged during trials was liver enzyme elevations in a small number of participants. The FDA requires liver function testing before starting fezolinetant and periodically during treatment. Fezolinetant is contraindicated in patients with hepatic impairment. This hepatic monitoring requirement distinguishes it from other non-hormonal options and adds a practical consideration to its use. Common side effects include abdominal pain, diarrhea, back pain, insomnia, and hot flashes at the start of treatment (which typically resolve).

Fezolinetant is taken as one 45 mg tablet once daily, orally. It does not interact with CYP2D6, making it safe to use with tamoxifen, which is a significant advantage for breast cancer survivors and high-risk women.

Tracking your symptoms over time, using a tool like PeriPlan, can help you monitor hot flash frequency and severity before starting fezolinetant and assess response at 12 weeks, the timeframe used in the clinical trials.

When to talk to your doctor: Discuss fezolinetant if you are seeking effective non-hormonal hot flash management, particularly if you have tried or cannot tolerate SSRIs, SNRIs, gabapentin, or clonidine. Your provider will need to check your liver function before prescribing. Mention any history of liver disease, alcohol use, or existing medications that are metabolized by CYP1A2 (fezolinetant is metabolized by this enzyme and can interact with certain medications).

This content is for informational purposes only and does not replace medical advice. Always consult your healthcare provider about your specific situation.