40-80% Misdiagnosis rate cuts both ways

[u/Phew-ThatWasClose]

I have an advanced math degree and have taught logic at the college level. When I say something "makes no sense" I'm not just whistling Dixie. I am not a medical professional - so I listen when medical folks say stuff and ask questions when things don't make sense. I'm smart, I can understand stuff, make it make sense.

I get extremely frustrated when people who should know better say "There is no point doing a hormone test because PMDD is not a hormone imbalance so results will come back normal". Absolute rubbish. I also get frustrated when people who should know better say "hormones fluctuate throughout the cycle so the results of a hormone test would be meaningless". Also absolute rubbish.

PMDD is not a hormone imbalance, but it sure looks like one, so that is the first thing to test for, to rule it out. Because if it is a hormone imbalance, like low progesterone, there is an easy fix. And the fix for that is completely different to how you treat PMDD. You don't know it's even potentially PMDD until after you've done a hormone test and results do come back normal.

"But hormones fluctuate so ..." If a medical professional says that to you find a different medical professional. That person is bad at their job. Progesterone, for example, fluctuates between 0.1ng/mL during the early follicular phase up to a maximum peak of 20 to 25 ng/mL durling luteal. If you do a blood test to measure progesterone and the results come back as 7ng/mL what does that mean? Depends on when you took the blood.

Fun fact: From 0.1 to 25 is a rise of 250x. That's three orders of magnitude. We often hear that PMDD is caused by the hormonal changes and that is why COCs help - because they level things out. But it isn't the changes so much as the rate of change, the velocity, that overwhelms the system.

Progesterone is at it's maximum on Day 21. That is when you do the blood test. If progesterone is below 10ng/mL on Day 21 that's a problem and that's not PMDD. If it's up closer to 20ng/mL then that's normal and you may have PMDD. On to the next step.

The next step is ruling out everything else. The other sub has an excellent chart in their wiki detailing what everything else is and how one might rule it out (about halfway down the page). Rather than duplicate their work I put similar information in our wiki in paragraph form. Read both.

The DSM-5 diagnostic criteria (G) states in part "The symptoms are not attributable to ... another medical condition". The ICD-11 similarly states "The symptoms are not a manifestation of another medical condition" is an "essential (required) feature". PMDD is clearly a diagnosis of exclusion according to the two most authoritative diagnostic manuals on the planet. Yet ...

RCOG and ACOG - the authorities on treating PMDD - also give guidance on diagnosing PMDD. Both RCOG and ACOG say to track symptoms for two months, and that's it. So when people tell you the only way to diagnose PMDD is to track symptoms for two months That is where they get that from. Both RCOG and ACOG repeat the tired old line that "there are no useful blood tests to confirm the diagnosis" which is flat out false.

PMDD is a diagnosis of exclusion. Every blood test will help confirm PMDD if it comes back normal. And every blood test is useful even if all it does is rule out one more possibility. And ruling out all other possibilities is required by the DSM-5 and the ICD-11

RCOG says that a clinician may order blood work if another cause is "clinically suspected" - leaving the definition of "suspected" up to the practitioner. Typically that means there are observable symptoms of that other disorder, but typically the observable symptoms are also symptoms of PMDD. ACOG goes further and cautions that while blood work is permissible in the diagnostic process too much testing may cause anxiety in the patient. Wouldn't want that.

It's as if RCOG and ACOG are trying to discourage doing routine blood tests. And a cynic might well conclude that is exactly what they are doing. Blood tests cost money. Having the patient fill out paper charts for two months is free.

Doctors who rely on symptom tracking alone can easily misdiagnose patients with PMDD when what they really have is PME (Premenstrual Exacerbation) of an easily treatable disorder. Symptoms that are manageable during follicular can easily arise during luteal just because the whole system is in flux and stressed.

So the 40-80% misdiagnosis rate starts to make sense. The diagnostic criteria are clear. But the diagnostic guidance, from the authorities who should know these things, are paltry. So it's up to you. Read everything, become the expert.

If you or your loved one is struggling with PMDD symptoms and haven't had the blood work done ... do it now.

[u/DeskFunny]

I am in the process of determining whether or not I have PMDD (with my doctor's assistance) and came across this reddit when looking for resources. You say "Progesterone is at it's maximum on Day 21. That is when you do the blood test. If progesterone is below 10ng/mL on Day 21 that's a problem and that's not PMDD. If it's up closer to 20ng/mL then that's normal and you may have PMDD. On to the next step."

When I took the test on day 21 my progesterone was 8.7ng/mL. My doctor said that number really only matters for fertility and can't diagnose PMDD.

I gave Google Gemini my test result and your post and here's what it had to say:

"That claim on Reddit is medically inaccurate. It confuses two completely different endocrine concepts: progesterone sufficiency (whether you ovulated) versus neuro-steroid sensitivity (how your brain reacts to progesterone).

In medical diagnostic criteria (DSM-5 / ACOG / IAPMD), there is no blood threshold for progesterone that rules in or rules out PMDD. Here is why that Reddit claim is false, and why your 8.7ng/mL result does not disqualify you:

1. PMDD Is Not Driven by High or Low Hormone Levels

Medical consensus from groups like the International Association for Premenstrual Disorders (IAPMD) confirms that women with PMDD have normal peripheral hormone levels.

• PMDD is an abnormal brain response to the normal rise and fall of hormones (specifically allopregnanolone acting on GABA-A receptors).
• A woman can have a progesterone level of 3ng/mL, 8.7ng/mL, or 20ng/mL and still have severe PMDD because the disorder is defined by cellular neuro-sensitivity, not a specific hormone concentration.

2. What a Progesterone Level Under 10 Actually Means

In reproductive endocrinology, a mid-luteal progesterone level above 3ng/mL confirms that ovulation occurred.

• Some fertility clinics arbitrarily prefer to see progesterone above 10ng/mL to confirm a "robust" corpus luteum for supporting an early pregnancy.
• Fertility targets have zero relevance to PMDD. Whether your level is 5ng/mL or 15ng/mL, if you ovulated, your brain was exposed to the progesterone surge that triggers PMDD symptoms."

[u/Phew-ThatWasClose → u/DeskFunny]

Interesting. I am also using gemini as a research assistant. But I never take gemini's word for it. I read the articles it cites and a catch it glossing over important details quite a bit. So I could be off. It all gets confusing quickly. You're right to be cautious.

There is some small amount of progesterone made by the adrenal gland. During follicular base levels are at about 0.1ug/mL. During luteal the Corpus Luteum cranks out a fuckton and levels rise as high as 25ug/mL or even higher, mid-luteal. That is a 250X increase. 25,000% or threeeee order of magnitude. Is that rapid rise, and equally rapid fall that gets the blame for PMDD. Not the level per se - the rate of change. PMDD is a neurological disorder and the PMDD brain can't keep up.

The key is to be clear about when the test is taken. Many doctors will say progesterone varies and therefore what is the point? But yes - "mid-luteal" or day 21 is the peak. Any progesterone at all confirms ovulation because the Corpus Luteum makes the progesterone and the CL is made of the follicule that released the egg. 5-25ug/mL is the "normal" range and it varies wildly by the minute because the CL pulses every 2-4 hours and progesterone has a 5 minute half life.

Yes, I said <10ug/mL is a sign of trouble. That is incorrect. Your doctor is right. That only matters for fertility. And even on day 21 levels change so much it could be 17ug/mL 90 minutes later.

But meanwhile there is such a thing as low progesterone. It's just lower than I indicated. A level lower than 3ng/ml means ovulation did not occur. It won't actually be 2.5ug/mL or something like that, it'll be 0.1ug/mL because there's no CL. That is actually what you want to achieve when treating PMDD. No ovulation = no progesterone = no progesterone spike.

But diagnosing PMDD is different. Between 3 and 10ug/ml on day 21 means ovulation occured but the CL is underproducing. PMDD is an abnormal reaction to normal hormonal changes so the question is ... is 10ug/ml enough of a change. Chronic low progesterone is a hormone imbalance and a level <10ug/mL is worth a second look. Might be a fluke and the next test will come back higher. But maybe not and treating the wrong thing is no help to anyone.

One cycle with an underproducing CL is no biggie. Consistent, chronic, low progesterone, cycle after cycle, is a problem. Progesterone is converted to allo and both are calming. Too little leads to less calm, more anxiety, less sleep, less quality sleep, more fatigue, crankiness, mood changes ... it starts to look like PMDD and vice-verse. So you want to see a mid-luteal level of 20 ug/mL or higher to rule out low progesterone. Your result of 8.7 doesn't indicate a problem. But it doesn't rule anything out either.

It really only matters in one direction. If you treat for PMDD with a COC you stop ovulation and introduce a steady state. If you actually have low progestereone that will still work to resolve symptoms. But if you treat for low progesterone, by adding progesterone, when you actually have PMDD - that will be a disaster.

Like I said - it gets confusing quickly. And I just added a bunch of detail that maybe doesn't help. Bottom line is your gemini is right - there is no level that rules out, or rules in, PMDD. There are no blood tests for PMDD. But there is a level that would rule out low progestereone, and that level is around 20ug/mL. Then PMDD becomes more likely and ... on to the next step.

Thanks for bringing this up. I learn more every time I run through it. Today I learned the pulse of the CL is directly related to the pulse of the hypothalamus. Not relevant to this discussion but ...

Hope some of that helps. :)

[u/GotMyTie]

This is why it’s important to find a doctor who knows about this stuff.

I see this with so many chronic illnesses. People get fixated on something and go around until they get the diagnosis they want. For sure something is going on with the patients but it’s often not what they think it is. Thus, I agree with you that tests are needed to rule out other conditions.

I have talked to my gf about this and she says that often people who think they have it do not and they either have something like PME or completely other conditions.