- Neurokinin B is a peptide that causes hot flushes. In a randomized crossover study, an intravenous infusion produced flushing in 8 of 10 healthy women, against 0 of 10 on vehicle (P = 0.0007), which is direct causal evidence obtained in women rather than inferred from men or animals.
- After estrogen withdrawal, KNDy neurons in the hypothalamic infundibular nucleus enlarge and increase their kisspeptin and neurokinin B expression, which is the mechanism linking menopause to the thermoregulatory misfire experienced as a hot flush.
- The treatments that came out of this pathway block the neurokinin 3 receptor and are small molecules, not peptides: fezolinetant was FDA-approved in May 2023 and elinzanetant, a dual NK-1/NK-3 antagonist, followed in 2025.
- Vasomotor symptoms affect roughly 65 to 75 percent of women after menopause, making this the best-characterized peptide mechanism in women's health and a useful benchmark for what real female evidence looks like.
Most of this database documents absence: compounds studied in men and sold to women, with the female column left honestly blank. This article is the opposite case, and it is worth reading precisely because it shows what the alternative looks like when a mechanism is properly worked out in women.
Hot flushes and night sweats, together called vasomotor symptoms, affect roughly 65 to 75 percent of women after menopause. They were treated for decades as a vague consequence of low estrogen. They are now one of the best-understood pathways in women's health, and the molecule at the center of it is a peptide.
The KNDy neuron
In the infundibular nucleus of the hypothalamus, in the region that also governs body temperature, sits a population of neurons that co-express three signals: kisspeptin, neurokinin B and dynorphin. From those initials they are called KNDy neurons. In a cycling woman, ovarian estrogen provides negative feedback that restrains them.
When that feedback is withdrawn at menopause, the restraint goes with it. The neurons hypertrophy, visibly enlarging in postmenopausal hypothalamic tissue, and increase their expression of kisspeptin and neurokinin B. They sit adjacent to the thermoregulatory center, and their overactivity spills into it. The result is a body that misreads its own core temperature and triggers a full heat-dissipation response, cutaneous vasodilation and sweating, in a woman who was not too hot.
The experiment that proved it
Mechanistic stories are cheap. This one is unusual because somebody tested it directly, in the population that has the symptom.
In a randomized, double-blind, placebo-controlled two-way crossover study, ten healthy women received a 30-minute intravenous infusion of neurokinin B and, on a separate occasion, vehicle, in random order. Eight of the ten flushed during the neurokinin B infusion. None flushed on vehicle (P = 0.0007). The episodes carried the elevations in heart rate and skin temperature that characterize a menopausal flush.
It is causal rather than correlational: the peptide was administered and the symptom appeared. It was done in women, for a condition women have, with the symptom itself as the endpoint rather than a surrogate marker. Ten participants is a small study, and it should be described as small. But it answers its question in the right population, which is more than most of the compounds in this database can say at any sample size.
The twist: the drugs are not peptides
Here is where the marketing usually goes wrong. Neurokinin B is a peptide, kisspeptin is a peptide, and the pathway is described in peptide terms throughout. It would be natural to conclude that the treatment is a peptide too. It is not.
The therapeutic move was to block the receptor that neurokinin B acts on, the neurokinin 3 receptor, and the molecules that do it are small-molecule antagonists. A phase 2 trial of an NK3 antagonist reported rapid reduction in vasomotor symptoms, and two drugs have since reached approval: fezolinetant (Veozah), approved by the FDA in May 2023 as the first NK3 receptor antagonist for moderate to severe menopausal hot flushes, and elinzanetant (Lynkuet), a dual NK-1/NK-3 antagonist approved in the United States in 2025.
| Molecule | What it is | Role in this story |
|---|---|---|
| Neurokinin B | Peptide (endogenous) | The cause. Infusing it induces flushes in women |
| Kisspeptin | Peptide (endogenous) | Co-expressed in the same KNDy neurons; central to reproductive-axis signaling |
| Fezolinetant | Small molecule (NK3 antagonist) | The treatment. FDA-approved May 2023 |
| Elinzanetant | Small molecule (dual NK-1/NK-3 antagonist) | The treatment. US approval 2025 |
What this means for reading everything else
Two things are worth carrying away from this pathway when you read about any other compound at this life stage.
- A mechanism involving a peptide does not imply a peptide treatment. The intervention can be, and here is, a molecule that blocks the peptide. Being able to tell those apart is most of the skill in reading this category.
- This is what adequate female evidence looks like, and it is a fair benchmark for the rest. A causal experiment in women, a symptom endpoint rather than a surrogate, and approved drugs whose trials enrolled the affected population. When a research compound is marketed for menopausal symptoms, the question is whether anything remotely like this exists behind it. For the compounds covered in perimenopause and menopause: what the peptide evidence actually says, the answer is usually no.
None of this is medical advice, and the approved drugs named here are prescription medicines that carry their own risks and monitoring requirements, including hepatic monitoring for fezolinetant. The point of the article is not what to take. It is what a properly answered question looks like, so the unanswered ones are easier to spot.