Evidence explainerMenopause & Perimenopause

Can't or Won't Take Hormones? The Non-Hormonal Hot Flash Treatments That Beat Placebo

Two new brain-targeted pills, an older list of repurposed drugs, and behavioral therapy all have trial data for hot flashes. Here is how they compare, and the side effects to watch.

By Kymata Health editorial teamPublished October 10, 2026Last verified October 10, 2026

Medical review pending. Written by our editorial team from the studies and documents cited below; a credentialed clinician has not reviewed it yet. Educational only, not medical advice.

Key takeaways

  • Fezolinetant 45 mg cut moderate to severe hot flashes by about 2.6 more per day than placebo at 12 weeks in SKYLIGHT 1 [1].
  • Elinzanetant 120 mg cut them by about 3.2 more per day than placebo at 12 weeks in OASIS 1 and 2, and improved sleep scores [2].
  • Veozah (fezolinetant) carries a boxed warning for rare but serious liver injury, with liver tests before and during treatment [3].
  • Lynkuet (elinzanetant) was approved in 2025 at 120 mg once daily at bedtime [4].
  • The 2023 nonhormone position statement also recommends CBT, clinical hypnosis, SSRIs or SNRIs, gabapentin and oxybutynin, and recommends against supplements and herbal remedies [5].

The new class: neurokinin blockers

Fezolinetant blocks the neurokinin-3 receptor in the brain's temperature-control circuit; elinzanetant blocks both neurokinin-1 and neurokinin-3 receptors [1][2].

In SKYLIGHT 1 (527 women aged 40 to 65 with 7 or more moderate to severe hot flashes a day), fezolinetant 30 mg and 45 mg reduced daily frequency by 2.39 and 2.55 more than placebo at week 12, with improvement visible after 1 week and maintained to 52 weeks [1].

In OASIS 1 and 2 (796 postmenopausal women), elinzanetant 120 mg reduced daily frequency by about 3.2 more than placebo at week 12 in both trials, and improved sleep disturbance and menopause quality-of-life scores [2].

The liver caveat

Fezolinetant was approved in May 2023 with a warning about elevated liver enzymes. After post-marketing cases of liver injury, the FDA issued a Drug Safety Communication in September 2024 and upgraded it to a boxed warning in December 2024 [3]. The FDA advises stopping the drug and getting tested for symptoms such as unusual fatigue, nausea, itching, yellow skin or eyes, pale stools or dark urine [3].

Elinzanetant's label lists 120 mg (two 60 mg capsules) once daily at bedtime [4]. It is newer, so its post-marketing safety record is shorter; ask your prescriber which liver tests they will order.

Older options that also work

The 2023 nonhormone position statement gives its strongest recommendation (Level I) to cognitive behavioral therapy, clinical hypnosis, SSRIs and SNRIs, gabapentin and fezolinetant, and Levels I to II to oxybutynin [5]. Weight loss and stellate ganglion block get weaker recommendations [5].

Each has trade-offs: some SSRIs interact with tamoxifen, gabapentin can cause drowsiness, and oxybutynin is an anticholinergic. That is a conversation for your prescriber, not a reason to skip treatment.

Quick answers

Is Veozah safe?

It beat placebo in phase 3 trials, but the FDA added a boxed warning in December 2024 for rare but serious liver injury, so liver tests are required [3].

How fast do the new pills work?

In SKYLIGHT 1, improvement in hot flash frequency was seen after 1 week [1]; in OASIS 1 and 2 the drop was significant by week 4 [2].

Can I use these after breast cancer?

Whether a non-hormonal drug fits after breast cancer is a decision for your oncology team; the phase 3 trials above were in postmenopausal women with moderate to severe hot flashes [1][2].

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References

  1. [1]Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet, 2023. PMID 36924778
  2. [2]Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA, 2024. PMID 39172446
  3. [3]FDA adds Boxed Warning for rare but serious liver injury with Veozah (fezolinetant). U.S. Food and Drug Administration, Drug Safety Communication, 2024.
  4. [4]LYNKUET (elinzanetant) capsules: prescribing information, initial U.S. approval 2025. U.S. Food and Drug Administration (Drugs@FDA), 2025.
  5. [5]The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause, 2023. PMID 37252752

Dietary supplements are not intended to diagnose, treat, cure or prevent any disease, and these statements have not been evaluated by the FDA. Prescription options need a licensed clinician. Talk to your clinician or pharmacist before starting anything new, especially if you take prescription medicines, are pregnant or breastfeeding.

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