Veozah (Fezolinetant) for Hot Flashes: How It Works and What to Expect

Veozah, the brand name for fezolinetant, is a non-hormonal prescription pill approved by the FDA in May 2023 specifically for moderate-to-severe vasomotor symptoms (hot flashes and night sweats) associated with menopause. Unlike hormone therapy, which works by replacing the estrogen your ovaries stop producing, fezolinetant works entirely differently: it's a neurokinin 3 (NK3) receptor antagonist that targets a specific neural pathway in the brain involved in temperature regulation, without touching hormone levels at all.

This distinction matters most for women who have medical reasons to avoid hormone therapy — a personal history of estrogen-sensitive breast cancer, a history of blood clots or stroke, or simply a strong personal preference to avoid hormones. It also matters for women who've tried hormone therapy and didn't tolerate it well, or who want a non-hormonal option to try first before considering HRT.

Fezolinetant targets a group of neurons in the hypothalamus (specifically KNDy neurons, which produce kisspeptin, neurokinin B, and dynorphin) that play a central role in regulating body temperature. Before menopause, estrogen keeps these neurons in check. As estrogen drops during the menopause transition, these neurons become overactive and enlarged, disrupting the hypothalamus's temperature set point — this is a major reason hot flashes happen: your body mistakenly senses it's overheating and triggers sweating and flushing to cool down, even when your actual body temperature hasn't changed.

Fezolinetant blocks the NK3 receptor, which neurokinin B binds to, effectively calming this overactive signaling without needing to replace estrogen at all. This is a genuinely novel mechanism — it was the first drug of its kind approved for menopause symptoms, representing years of research into the neuroscience of vasomotor symptoms rather than simply another hormonal approach.

The SKYLIGHT 1 and SKYLIGHT 2 trials, published by Lederman et al. in The Lancet in 2023, were randomized, placebo-controlled trials enrolling women with moderate-to-severe vasomotor symptoms. Both trials found fezolinetant 45mg significantly reduced the frequency of moderate-to-severe hot flashes compared to placebo as early as week 1, with effects continuing to improve and remaining significant through week 12, the primary endpoint. Hot flash severity also improved significantly. A companion long-term safety trial, SKYLIGHT 4, followed participants for up to 52 weeks and supported the durability and general safety profile of continued use.

Participants in the fezolinetant groups reported meaningful improvements not just in raw hot flash counts but in sleep disruption caused by night sweats and in quality-of-life measures related to vasomotor symptoms — reflecting that the drug's benefit extends beyond simply counting fewer flashes to actually improving daily functioning.

The most common side effects reported in trials were abdominal pain, diarrhea, insomnia, back pain, and hot flushes during the initial adjustment period. The most important safety consideration is a small risk of elevated liver enzymes, observed in a subset of trial participants, which is why the FDA label requires baseline liver function testing before starting, followed by monitoring at months 3, 6, and 9 of treatment. Most elevations were asymptomatic and resolved after stopping the medication, but this monitoring schedule is a real commitment, not optional paperwork.

Fezolinetant also has some drug interaction considerations, particularly with CYP1A2 inhibitors (including some antidepressants and the birth control pill component ethinyl estradiol combined with certain progestins), so it's important to review your full medication list with your prescriber. It's not recommended for use during pregnancy or in women with severe kidney or liver impairment.

Good candidates for fezolinetant include women with moderate-to-severe hot flashes and night sweats who have a personal or family history that makes hormone therapy higher-risk (certain breast cancers, blood clot history), women who prefer to avoid hormones on principle, and women who've tried HRT and experienced side effects they didn't tolerate. It's also a reasonable first option to discuss alongside HRT for anyone simply weighing choices, since it doesn't foreclose starting hormone therapy later.

It's not typically the first choice for women who also want the bone density, vaginal, or broader systemic benefits that estrogen therapy can provide, since fezolinetant is specifically targeted at vasomotor symptoms and doesn't address those other domains. A telehealth menopause specialist or your regular OB/GYN can prescribe it after reviewing your history and baseline liver labs, and it's worth discussing your specific priorities so you land on the option, or combination, that fits your actual situation rather than defaulting to whichever one you heard about first.