If you’ve ever been mid-conversation when the heat rose through you like a wave—sudden, fierce, leaving you flushed and wondering if anyone noticed—I want you to know: we finally understand why.
For decades, hot flashes were dismissed as mysterious, psychosomatic, “just something that happens.” But science has caught up to what your body already knew. And the answer lies in a tiny cluster of neurons deep in your brain.
The Discovery That Changed Everything
In the early 2000s, researchers discovered a group of neurons in the hypothalamus that they named KNDy neurons (for kisspeptin, neurokinin B, and dynorphin—the signaling molecules they use).
These neurons sit right next to your brain’s thermostat. And they have estrogen receptors.
Here’s what happens:
When estrogen is present, it keeps these neurons calm. But when estrogen drops—or, crucially, when it fluctuates—these neurons become hyperactive. They flood your thermoregulatory center with neurokinin B, essentially narrowing your body’s comfort zone to almost nothing.
Normally, your body tolerates a range of temperatures before deciding you’re too hot or too cold. During perimenopause, that range shrinks dramatically. A change that wouldn’t have registered before now triggers your body’s full heat-dissipation response: blood vessels dilate, sweat pours, your skin flushes.
That’s a hot flash. It’s not in your head. It’s in your hypothalamus.
Why This Matters for Understanding Your Experience
This discovery explains things we couldn’t explain before:
Why withdrawal matters more than level: It’s not just low estrogen that causes symptoms—it’s the drop. Rapid fluctuations are more symptomatic than stable low estrogen. This is why early perimenopause, when hormones swing wildly, can feel worse than being firmly postmenopausal.
Why some women never get hot flashes: Individual variation in these neurons and their sensitivity to estrogen means some women sail through while others are drenched nightly. Neither is imagining anything.
Why new medications work: There’s a new class of drugs (NK3 receptor antagonists) that can block hot flashes without providing any estrogen at all—by directly calming these neurons. This is proof that the mechanism is real and targetable. (More in Support Options.)
The Mood Connection: Emerging Research
Here’s something else we’re learning—and I’ll be honest that the research is still emerging, but it’s too important not to share:
FSH itself may directly affect mood.
We used to think depression and anxiety during perimenopause were simply due to estrogen changes. But newer studies (2024-2025) suggest that rising FSH—independent of estrogen levels—correlates with depressive symptoms.
What we know:
- Perimenopausal women have 2-3 times higher risk of depression than premenopausal womenBromberger JT, et al. Depressive Symptoms During the Menopausal Transition: The Study of Women's Health Across the Nation (SWAN). Journal of Affective Disorders. 2007;103(1-3):267-272.
- The longer your perimenopause lasts, the higher your risk
- Interestingly, a rapid rise in FSH may actually be protective—a shorter transition seems easier on mood
- Women who were sensitive to hormonal mood changes before (severe PMS, postpartum depression) are at higher risk during perimenopauseBromberger JT, Epperson CN. Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstetrics and Gynecology Clinics of North America. 2018;45(4):663-678.
The Estradiol Variability Hypothesis
Some researchers now believe it’s not the level of estrogen that affects mood, but how sensitive you are to changes in estrogen. The direction, the speed, the magnitude of change.
This explains why:
- The chaotic transition is often harder than stable postmenopause
- Stabilizing hormone levels—even at low levels—often helps mood
- What helped for PMS might help now
- Your friend with similar hormone levels might feel completely different
What This Means for You
Your brain fog is real. Your mood changes are real. Your sleep disruption is real. These aren’t character flaws or failures of will. They’re your brain responding to a profound neurochemical shift.
Understanding this doesn’t make symptoms disappear. But it can help you stop questioning yourself. It can help you make informed choices about support strategies. And it can help you explain to others—partners, doctors, yourself—that what you’re experiencing has a biological basis.
Your brain is adapting to a new hormonal reality. It takes time. And you deserve support while it does.