Clinical comparison · Menopause & vasomotor symptoms · Updated 2026-07-02
Fezolinetant is a non-hormonal NK3-receptor antagonist for menopausal hot flashes; estradiol is hormone therapy. This table reproduces labeled and trial-reported facts verbatim, per cell. Their pivotal trials used different designs and endpoints, so the numbers are not a direct head-to-head. The page does not recommend one over the other.
Every value below is reproduced verbatim from an FDA prescribing-information document or a published clinical trial, and each cell links to its source. This page does not rank the two options, does not declare one safer or more effective, and is not medical advice.
| Dimension | Fezolinetant | Estradiol |
|---|---|---|
| Drug class | Neurokinin-3 (NK3) receptor antagonist — non-hormonal[1] | Estrogen (bioidentical 17-beta-estradiol)[2] |
| FDA-approved use | Moderate-to-severe vasomotor symptoms due to menopause[1] | Moderate-to-severe vasomotor symptoms; other menopausal indications[3] |
| Pivotal VMS efficacy | VMS frequency reduced ~6.3/day at week 12 vs ~3.7 placebo (45 mg, SKYLIGHT 1)[1] | Estrogen reduces hot-flash frequency by ~75% vs placebo (class data)[2] |
| Boxed / serious warning | Boxed warning (2024): rare serious liver injury; monitor LFTs[4] | No boxed warning; VTE and stroke listed as serious risks (route-dependent)[2] |
| Route | 45 mg oral tablet once daily[1] | Transdermal patch/gel, oral tablet, or vaginal[3] |
| Pregnancy | Indicated only for postmenopausal women; not studied in pregnancy[1] | Contraindicated in pregnancy (FDA category X)[3] |
What SKYLIGHT 1 measured
SKYLIGHT 1 (Lederman et al., The Lancet 2023) was a phase 3 placebo-controlled trial of fezolinetant that measured change in daily moderate-to-severe vasomotor-symptom frequency and severity. For the 45 mg dose it reported a least-squares-mean reduction of about 6.3 episodes/day at week 12 versus about 3.7 with placebo — a placebo-adjusted difference of about 2.55 fewer episodes/day (p<0.001). SKYLIGHT 1 (Lancet 2023)
Why the numbers are not directly comparable
The fezolinetant figure is an absolute change in episodes/day from SKYLIGHT 1; the estrogen figure is a percentage reduction summarized across estrogen trials. Different metrics, populations, and eras mean these are not a head-to-head result. NAMS 2022 Hormone Therapy Position Statement
No. Fezolinetant is a non-hormonal neurokinin-3 (NK3) receptor antagonist approved for moderate-to-severe menopausal hot flashes (FDA Veozah label).
Yes. In 2024 the FDA added a boxed warning for rare but serious liver injury and advised liver-function monitoring (FDA Veozah label, 2024).
In SKYLIGHT 1, fezolinetant 45 mg reduced moderate-to-severe hot-flash frequency by about 6.3 episodes per day at week 12 versus about 3.7 with placebo — a placebo-adjusted difference of roughly 2.55 fewer episodes per day (The Lancet, 2023).
Editorial reviews from ClearHormones of telehealth providers in this category. These are not treatment recommendations, and prescribing decisions rest with a licensed clinician.