Hot Flushes: What's Happening in the Brain

A hot flush feels like it originates in your skin. It doesn't. It originates in a small cluster of neurons in your hypothalamus, and understanding what those neurons are doing explains both why flushes feel so strange and why an entirely new class of drug now exists to switch them off.

The thermostat, narrowed

Your body maintains core temperature within a narrow band. Above the top of that band you sweat and your blood vessels dilate to dump heat. Below the bottom you shiver and your vessels constrict. Between the two is the thermoneutral zone — where you do nothing at all, because nothing is required.

In women having hot flushes, that zone appears to be dramatically narrowed. A rise in core temperature so small you'd never consciously register it now crosses the ceiling, and the full heat-dumping response fires: blood vessels in the skin open, sweating starts, heart rate rises. Then the overcorrection — you've shed real heat, you drop below the floor, and you get the chill and the shiver that follows a flush.

This is why flushes feel disproportionate. The response isn't broken. It's a correctly executed emergency response to a temperature change that shouldn't have qualified as an emergency.

The neurons responsible

The mechanism sat unexplained for decades. What changed came from an unexpected direction — research into a group of neurons in the hypothalamic arcuate nucleus known as KNDy neurons, named for the three substances they produce: kisspeptin, neurokinin B and dynorphin.

These neurons are ordinarily restrained by estrogen. When estrogen falls, they enlarge and become hyperactive — an effect observed in post-mortem tissue from postmenopausal women. They sit immediately adjacent to the brain's thermoregulatory centre, and their hyperactivity, signalling through neurokinin B, appears to be what narrows the thermoneutral zone.

That finding produced a testable prediction: block the receptor that neurokinin B acts on, and flushes should reduce without touching estrogen anywhere in the body.

The drugs that came out of it

The prediction held.

Fezolinetant, an NK3 receptor antagonist, was approved by the FDA in May 2023 as the first non-hormonal drug of this class for moderate to severe hot flushes. Elinzanetant, which blocks both NK1 and NK3 receptors, followed — approved in the UK, Canada, Australia and Switzerland, and by the FDA in October 2025.

Both reduce flush frequency and severity substantially in trials. Both are non-hormonal, which matters for women who can't take estrogen — including many breast cancer survivors, in whom treatment-induced flushes are often severe.

They aren't automatically the right choice. Hormone therapy remains the most effective treatment for hot flushes, fezolinetant requires liver monitoring, and both are new enough that long-term data is still accumulating. But the existence of a mechanism-targeted alternative is a genuine change in the landscape, and worth knowing exists.

What a flush actually does to you

Physiologically: skin blood flow increases sharply, sweating begins, heart rate rises by perhaps seven to fifteen beats per minute, and skin temperature climbs while core temperature falls slightly. Most last one to five minutes.

Frequency varies enormously. Some women get two a week. Some get twenty a day. Around three quarters of women experience them at some point.

There's also an anticipatory element that's easy to underestimate. If you've had a flush in a meeting, you enter the next meeting alert to the possibility, and that alertness is itself physiologically arousing. This isn't a claim that flushes are psychological — they demonstrably aren't. It's part of why cognitive behavioural therapy, which addresses the response to the flush rather than the flush itself, produces measurable benefit and is now recommended in NICE guidance.

What doesn't work as well as you'd think

The Menopause Society reviewed the non-hormonal evidence in 2023 and reached some conclusions that contradict standard advice.

Avoiding triggers: not recommended, on the current evidence. Cooling techniques: not recommended. Paced breathing: not recommended. Exercise, specifically as a treatment for flushes: not recommended — which is not an argument against exercise, which is good for a great many other things, just not demonstrated to reduce flushes.

Supplements and herbal remedies, including black cohosh and soy extracts: not recommended.

What did make the recommended list: cognitive behavioural therapy, clinical hypnosis, certain SSRIs and SNRIs, gabapentin, fezolinetant, oxybutynin, and weight loss in women with higher body weight.

None of that means your cotton sheets and your desk fan are wasted. Comfort is worth having. It means that if you're managing flushes primarily through avoidance and they're still dominating your life, the problem is not your discipline. It's that avoidance was never a very effective treatment.

Sources

- Rance NE, Dacks PA, Mittelman-Smith MA, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy neurons. Frontiers in Neuroendocrinology. 2013;34(3):211–227. - The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause. 2023;30(6):573–590. - US Food and Drug Administration. Approval of fezolinetant (Veozah), May 2023; approval of elinzanetant (Lynkuet), October 2025. - National Institute for Health and Care Excellence. Menopause: identification and management (NG23), CBT recommendations. Updated 2024. - Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. Journal of Steroid Biochemistry and Molecular Biology. 2014;142:115–120.