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E2 Reference Range 25.8 - 60.7 pg/ml - Is this Wrong?

NOTE: I want to focus the discussion on E2 even though I’m including my entire TRT protocol.

I read that the E2 reference range is 25 - 60 pg/ml. this is the reference range used by my clinic. But almost every post I read here seems to suggest this reference range is wrong…and that anything above 30 is too high.

Are there different ways of measuring E2 or is my clinic using some outdated or inaccurate reference range?

My e2 was 32 before starting any kind of therapy.

I’m 36 years old, so I tried a trial of HCG monotherapy at 500iu EOD, where my E2 went up to 46 after the first week.

I got put on an AI once a week. Eventually E2 got down to 33. after a couple more weeks.

After about 2 months on HCG mono I decided it wasn’t for me. I was moody and just felt off even though my energy levels increased. I did a final blood test before switching to TRT and my e2 was at 40.

Then I switched to TRT, and this was 5 weeks ago.

-62.5 mg testosterone 2X a week
-HCG 500IU 2X a week
-arimidex 0.125mg 2x a week.

After two weeks on this, my E2 went down to 23 pg/ml:

Total T: 1304 (lab tested only one day after injection…this was a misunderstanding, I should have waited another 2 or 3 days)

E2: 23 pg/ml (took a 0.125 arimidex pill the previous day)

And honestly…I felt better during this time…like my mood was more stable then before.

23 pg/ml is below their ref range of 25.8 to 60.7 pg/ml, so my doc told me to take the arimidex of 0.125 only once a week.

She also lowered my tesosterone dosage to 100mg /week since it was above therapeutic levels.

So since we were changing my protocol, she wanted to have another lab test done in 2 weeks…which we did and the results came at:

E2: 40 pg/ml
Total T: 1080 ng/dl

So the E2 went from 23 to 40 in 2 weeks after halfing the AI dosage. This worried me.

My doc said to continue this protocol. She thinks 40 should be where I should keep my E2.

But here’s the thing: I just felt much better during the time I tested at 23 pg/ml…my libido felt better, I had more frequent and stronger morning wood. And I could get out of bed much more easily.

So having experienced being at levels in the low 20s, low 30s, and low to mid 40s…and I can say that I think I felt best when I was in the 20s.

It’s been 2 or 2.5 weeks since I switched to 0.125 only once a week…and I feel much worse, especially in the mornings, starting about a week ago.

My doctor wants my next lab test to be in one month. But my concern is that if my e2 went from 23 to 40 in 2 weeks just after halfing my dose…I worry it will continue to go up to the 50s or 60s in a month.

So what do you think? Am I jumping to conclusions by blaming my condition on E2…could it be the exogenous testosterone at 5 weeks hasn’t stabilized yet?

Could be.

There are two different estrogen tests, there’s the Liquid Chromatography–Mass Spectrometry and the Roche ECLIA methodology and both have different ranges.

If you haven’t injected the same dosage for at least 6 weeks, then your levels aren’t stable. If you doctor changed the dosage of T at anytime within that 5 weeks, you just hit the reset button and now must wait another 6 weeks for levels to become stable.

Anytime you change the dosage, even if you’ve been on TRT for years, you have to allow 6 weeks until your body adapts to the new dosage.

Okay so the Roche ECLIA methodology is the one that measures between 8 pg/ml to 40 pg/ml and I’m assuming (couldn’t find any result) the liquid chromatography mass spectrometry range is 25 to 60 pg/ml.

How to people on TRT decide which reference range to go by? They just let their doctor/hospital choose for them? It sounds like people here mostly go by the Roche reference range.

My E2 was 32 pg/ml before using any HCG or testosterone. So perfectly normal by one reference range but a little bit high going by the other.

Here are a few examples of both tests run concurrently:

IA%20LC%2028-27%20clear IA%20LC%2041-53

The ECLIA test (aka immunoassay or IA) for E2 management is commonly used for those on TRT. It is not an incorrect test or a test for women, but simply one way to check estradiol levels. The other commonly utilized test is the LC/MS/MS method (aka liquid chromatography dual mass spectrometry, sensitive or ultrasensitive). It is the more expensive of the two. There are inherent advantages and disadvantages to each of these two methods. I have been fortunate to be able to speak with professionals who work with both methods. One is a PhD researcher for Pfizer and the other is a medical doctor at Quest. I’ll summarize their comments.

The ECLIA method is the more reliable of the two in terms of consistent results. The equipment is easier to operate thus accuracy is less reliant on the skill of the operator. If the same sample were to be tested twenty times, there would be very little, if any, difference in the results.

The ECLIA method is not as “sensitive” in that it will not pick up E2 levels below 15pg/mL. If your E2 level with this test is 1-14pg/mL, the reported result will be “<15”. Because of this, it is not recommended for menopausal women, men in whom very low levels of E2 are suspected, or children. In other words, if your levels are below 15pg/mL, and it is important to know if the level is 1 or 14pg/mL, you do not want this test. For us, this is likely moot, since if you are experiencing low E2 symptoms and your test comes back at <15, you have your answer. For a woman being treated with anti-estrogen therapy for breast cancer, it may be necessary to know if the E2 level is zero or fourteen because therapeutically, they want zero estrogen.

A disadvantage to IA testing is that it may pick up other steroid metabolites, which in men would be very low levels, but still could alter the result. Another potential disadvantage is that elevated levels of C-reactive protein (CRP) may elevate the result. CRP is elevated in serious infections, cancer, auto-immune diseases, like rheumatoid arthritis and other rheumatoid diseases, cardiovascular disease and morbid obesity. Even birth control pills could increase CRP. A normal CRP level is 0-5 to 10mg/L. In the referenced illnesses, CRP can go over 100, or even over 200mg/L. Unless battling one of these serious conditions, CRP interference is unlikely.
The LC/MS/MS method will pick up lower E2 levels and would be indicated in menopausal women and some men if very low E2 levels are suspected and it is desired to know exactly how low, children and the previously mentioned women on anti-estrogen therapy. It will not be influenced by elevated CRP levels or other steroid metabolites.

While some may believe the ECLIA test is for women, on the contrary, as it pertains to women on anti-estrogen therapy, such as breast cancer patients, the LC/MS/MS is the test for women as CRP levels are a consideration and it is necessary to know if the treatment has achieved an estrogen level of zero.

On the other side of the coin, LC/MS/MS equipment is “temperamental” (as stated by the PhD who operates both) and results are more likely to be inconsistent. Because of this, researchers will often run the same sample multiple times.

It is not clear if FDA approval is significant, but this appears on Quest’s lab reports: This test was developed, and its analytical performance characteristics have been determined by Quest Diagnostics Nichols Institute San Juan Capistrano. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. This statement is on LabCorp’s results: This test was developed and its performance characteristics determined by LabCorp. It has not been cleared by the Food and Drug Administration.

It is unlikely that any difference in the same sample run through both methods will be clinically significant. Estradiol must be evaluated, and it should be checked initially and ongoing after starting TRT. It obviously makes sense to use the same method throughout. Most important are previous history and symptoms related to low or high E2. Those are correlated with before and after lab results. Any estradiol management should not be utilized without symptoms confirmed by lab results.

Heres my reference range. Does that help? I’m in the US and this is LabCorp’s ranges for sens E2.


Ok I misunderstood and got the methods reversed. Here are my labs and range


lab an reference range

Are you in the US? I have never seen 25 to 60 before. Maybe your clinic does their own blood analysis.

I’m in Thailand. I also found this: https://tctmed.com/normal-estradiol-levels/

The Range of Normal Estradiol Levels in Men

For men, normal total estradiol levels are somewhere between 20–55 pg/mL (2.0–5.5 ng/dL) and 10-40 pg/mL (1.0-4.0 ng/dL), depending on who you ask.

The first range is based off a study of the total estradiol levels of 115 healthy men. You can read the study in its entirety here.

The same study with the same group of men found that free estradiol levels ranged between 0.3–1.3 pg/mL (0.03–0.13 ng/dL).