Can your oestrogen be "normal" and still cause symptoms?
Yes. And this case is the clearest example I've seen of why.
A patient came to me after four years of being told her results were fine. Not borderline. Not "let’s test again." Fine. Oestradiol sitting at a genuinely reasonable level for her stage of perimenopause, progesterone was low normal, nothing flagged on any panel, nothing obvious to fix.
Meanwhile she couldn't hold a sentence together. Her mood swung without warning, not into rage, but a dark depressive state. Her memory had gone. She described waking up as a different person most days, with no way to predict which one.
Two things can be true at once. Her levels were fine. She wasn't.
The story perimenopause content keeps telling
If you've spent any time on socials scrolling through perimenopause content, you've likely run into a particular version: progesterone falls first, oestrogen stays high or erratic for a while, and most symptoms come from the imbalance between them. The opposition of oestrogen to progesterone ratios.
That version is often correct. Progesterone does frequently decline first, because ovulation becomes less reliable before oestrogen production winds down. Anovulatory cycles, where you don’t release an egg, produce no corpus luteum, which means no meaningful progesterone. That's real, it's common, and it explains a large number of women.
It didn't explain her.
Her picture started earlier in the cycle. The instability wasn't confined to the second half of her cycle in the way a luteal-phase progesterone deficiency usually presents, the way they tell you perimenopause goes. It was there in the follicular phase — the part of the cycle that's “supposed” to be the stable stretch, where oestrogen climbs steadily toward ovulation.
I use the term follicular phase deficiency for this pattern, or frankly, the Canary in the Coal Mine. It isn't a formal diagnostic category, and you won't find it in a textbook — it's how I describe a picture I keep seeing in clinic, where the disruption sits in the first half of the cycle rather than the second, and where the standard progesterone-first framing doesn't fit the symptoms.
The Clue Everyone Had Missed
Before she got to me, more than one practitioner had tried to "balance" her hormones. That usually means the same thing: assume oestrogen is too high relative to progesterone, push clearance, support detoxification pathways, bring the oestrogen down.
Simples. Not in perimenopause, and certainly not for this patient.
Every time they pushed, she got dramatically worse. Mood and memory both. Not a mild adjustment period — a cliff.
That reaction is information. You don't crash that hard on clearance support unless you were depending on every bit of oestrogen signal you had. It's the opposite of what you'd expect from someone with too much.
This is where the "oestrogen is the enemy" idea does real damage. It's a persistent belief in parts of naturopathy, and it leads to prescriptions aimed at lowering a hormone that is, in fact, doing enormous load-bearing work — in the brain, the bones, the blood vessels, and the womb space tissue. The symptoms usually blamed on oestrogen are more often oestrogen without adequate progesterone to oppose it, or oestrogen that isn't clearing efficiently. Those are different problems with different solutions.
Testing the receptors instead of the hormone
When someone's presentation is this unusual, and when standard interpretations have already failed twice, guessing gets expensive. Supplements aren't cheap. Neither are the months lost to a prescription that was never going to land.
So we tested her genetics. Not to diagnose anything — genetics doesn't diagnose. To find out whether the way her body handles oestrogen could explain a picture that made no sense on paper.
Oestrogen receptors
ESR1 (oestrogen receptor alpha) — rs2234693 (PvuII), rs9340799 (XbaI), rs2144025
ESR2 (oestrogen receptor beta) — rs4986938, rs1256049
GPER1 / GPR30 (membrane oestrogen receptor) — rs11544831
Variants across all three receptor types. Not one system, several.
And for her, that environment made sense of the pattern: a receptor system responding sharply to change. Which means she felt every shift in oestrogen, in a life stage defined by nothing but shifts.
Perimenopause is a bad time to be this sensitive to oestrogen fluctuation.
*A note on what this means. No single one of these variants predicts how a woman will feel. What they do is describe the environment the hormone is landing in.
Then the dopamine layer
She also has ADHD, which is its own thread in this — and one very few people are connecting.
DRD2 / ANKK1 — rs1800497 (Taq1A)
SLC6A3 / DAT1 — rs28363170
The relevant part is what oestrogen does to that system. Oestradiol modulates dopamine via multiple mechanisms. It's also why so many women with ADHD report their symptoms becoming markedly harder to manage through perimenopause, and why symptom severity can track the menstrual cycle.
So: a dopamine system already running lean, sitting underneath an oestrogen signal that swings unpredictably and lands unusually hard.
That isn't two separate conditions. It's one problem wearing two names. And can you imagine this hitting in perimenopause?
And vitamin D, which nobody tests properly
Her serum vitamin D wasn't the interesting part. She had a history of it dropping heavily in winter and rarely did it rise with supplementation, red-flag #1.
VDR (vitamin D receptor) — rs2228570 (FokI), rs1544410 (BsmI)
CYP2R1 (hepatic 25-hydroxylase) — rs10741657, rs10766197
CYP27B1 (renal and neuronal 1α-hydroxylase) — rs10877026
Which raises the obvious point: a serum vitamin D result tells you what's in circulation. It doesn't tell you what's being activated, or what the receptor does with it once it arrives.
It also links us back to her ADHD picture as well as her challenges with depressive type symptoms. Vitamin D is linked to both dopamine and serotonin. This woman really stood no chance.
The pattern underneath all three
Adequate on paper. Not translating in the body.
Oestrogen present, but a receptor environment that made every fluctuation felt. Dopamine already narrow, and dependent on an oestrogen signal that’s not going to hold until post menopause, are we really waiting 10 years? Vitamin D circulating, with the activation and receptor steps in question.
Three systems, one theme. Which is why "your levels are fine" kept being true, and kept leaving her helpless.
One more layer worth naming
Progesterone doesn't only calm things down. It changes how oestrogen receptors behave — progesterone down-regulating oestrogen receptor expression is well established in the womb space; this is why we have lighter bleeds when progesterone is adequate and why we see changes in our breasts over the cycle. The receptors dance with each other.
Whether that translates directly to receptor behaviour in the perimenopausal brain is not something anyone has measured (not that I can find anyway). I want to be clear that this is inference, not a documented finding.
But if it holds even partially, then as her progesterone shifted, the receptor environment shifted underneath it. Meaning, when progesterone drops it’ll further influence her ability to feel oestrogen properly.
What we actually did
Support aimed at the receptor environment and the systems around it, rather than at moving a number that was never the problem.
She's currently supported with targeted phyto-oestrogens, alternating cyclically between Estrovera, and standardised Soy Isoflavones and specific dietary interventions - fibre diversity, meeting protein targets, and carb cycling.
We are targeting vitamin D repletion with co-prescribed Magnesium and K2.
Additional support is aimed at supporting her brain and capacity with adaptogens, nervines, supporting methylation, and zinc and creatine supplementation. As well as weight training three times weekly.
She is also, in my assessment, a strong candidate for MHT — and that's a conversation for her and her doctor. I work alongside prescribing, not instead of it. Body-identical oestradiol therapy doesn't top up a deficiency in a case like this. Alike the plant oestrogen’s, it puts a buffer in to stabilise her. For a woman whose receptors respond to every swing, stability is the main aim, not supplementation.
What to take from this
Genetics didn't diagnose her. It confirmed a pattern that was already visible in her history and her response to treatment, and it stopped us guessing.
It allowed us to understand why a woman with a perfectly fine hormone panel woke up as a different woman every morning.
Melissa White, BHSc Naturopathy — perimenopause naturopath, Toowoomba | telehealth Australia-wide.
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This article is educational and not a substitute for individual medical advice. Genetic variants described here are association-level findings and do not diagnose any condition.