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Labs Inside. E2 vs E2 Sensitive. What about "Estradiol, Free"?

TRT Protocol has been 40mg Test Cyp e3d. No AI. I had been on this protocol for 3 weeks before I completed the labs below. I recently did a few labs and this is what came up:

04/30/2019 , Labcorp, ordered by general practitioner

Estradiol, Serum, MS

15 pg/mL, Reference Range: Adult Males: 8.0 - 35

04/30/2019 , Quest Diagnostics, ordered by myself at DirectLabs.com

Estradiol, LC/MS/MS

27 pg/mL, Reference Range: Adults: < OR = 29

Estradiol, Free

0.56 pg/mL, Reference Range: Adults < OR = 0.45

The above labs were taken 3 hours apart, at 2 separate locations. All other labs show that everything else is within range (including Prolactin, Free T, Total T, etc., SBHG, thyroid, etc.)

So what gives?

I think that the first lab was a “standard E2” test and not the “sensitive E2” test that is suggested here. The 2nd lab is the “sensitive E2” test suggested by some here: https://directlabs.com/TestDetail.aspx?testid=974

The “sensitive” E2 number is substantially higher than the “standard” E2 number.

Questions:

  1. Should I guide my protocol according to the 1st (MS [standard]) E2 test or the 2nd (LC/MS/MS [sensitive]) test? The 2nd lab is the “sensitive E2” test and the number is substantially higher than the “standard E2” lab. Either way, both E2 ranges are within normal limits, so I’m not super worried…

2) …However, what about my “Estradiol, Free”? That was above the reference range and is considered high, according to Quest Diagnostic reference range. Is “Estradiol, Free” something I should be concerned about? Should I adjust my TRT protocol accordingly in order to bring “Estradiol, Free” down?

As always, any and all input is greatly appreciated.

Thanks again.

You should be guided by how you feel and assign it to your labs. If you estrogen feels high, then it’s no surprise since free estrogen is elevated.

SHBG may be in range, but low normal and high normal SHBG can affect free testosterone by 50%, so in range doesn’t provide much detail about how you bind androgens. If SHBG is on the lower end, more frequent injections may be best.

I as well have seen bogus sensitive E2 labs, my latest scored high and felt like it was on the lower end. You could argue your E2 is somewhere in the middle of those two different labs tests.

If you did labs everyday, you would see a different level, your levels are not static numbers forever flat, they fluctuate like a moving target and are always changing. Another thing, there is no normal range for free E2, so for this fact you can only assign your number to yourself and not anyone else (population).

Your protocol should always be guided by how you feel.

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.

My most recent E2 labs with both methods. Immunoassay has been in the 50s, LC/MS/MS has been in the 70s. Note the CRP.

IA%20LC%2050-71

This may help you with E2.

I compared a sensitive vs non-sensitive test on Quest; same day; same blood draw, same lab. The results are here. They are different and confusing.