Why All Men Should be Tested with the Sensitive Estradiol Test

[Bevaklp]

I didn't know that! Thanks.

 

[DragonBits]

My Estradiol measured less than 5 pg/ml on the standard test (Roche ECLIA) with a range of 7.6-42.6. Since my estradial is already too low, what is the point of finding out exactly how low it actually is?

 

[CoastWatcher]

My Estradiol measured less than 5 pg/ml on the standard test (Roche ECLIA) with a range of 7.6-42.6. Since my estradial is already too low, what is the point of finding out exactly how low it actually is?

I presume you will be testing again, since you need to monitor estradiol. When you do, only the sensitive, LC, MS/MS, test should be used.

 

[Dr Justin Saya MD]

My Estradiol measured less than 5 pg/ml on the standard test (Roche ECLIA) with a range of 7.6-42.6. Since my estradial is already too low, what is the point of finding out exactly how low it actually is?

Good point...the problem is you don’t REALLY know the estradiol is that low without using the LC-MS/MS. The standard RIA estradiol is often purported to overestimate E2 levels relative to the sensitive assay, but I’ve seen it go both ways many times. Main point being the standard assay is just less accurate (assuming the LC-MS/MS is done correctly).

 

[DragonBits]

Good point...the problem is you don’t REALLY know the estradiol is that low without using the LC-MS/MS. The standard RIA estradiol is often purported to overestimate E2 levels relative to the sensitive assay, but I’ve seen it go both ways many times. Main point being the standard assay is just less accurate (assuming the LC-MS/MS is done correctly).

I agree with you that the LC-MS/MS method is more accurate, and especially so for lower levels of E2. Though in my case it’s a moot point.

Partly I asked the question because I was wondering if there any value to knowing if my E2 was 2 pg/ml or 4 pg/ml or even 10 pg/ml?

I don’t see any value to knowing that, and the only reason at this time I wanted to know was intellectual curiosity.

Moot point because I do not have any exogenous testosterone in my system, and my free testosterone measured 5.5 pg/ml (Roche ECLIA methodology) and my TT was 390 ng/dl (LC/MS-MS method). Which would explain my low E2. (LH 3.6 mIU/mL)

If I were ordering testosterone independent of a doctor/clinic I would do so based on the evidence I have right now. But I already know my medical history for the past 8 years, while a doctor tends to treat a new patient as if they were a newly created human. Meaning they want to start from ground zero.

My reason for getting on this forum was to determine the best method to restart TRT. I had previously been on Nebido for 5 years, but it was mostly independent of a doctor. A doctor in Asia gave me my first injection, he didn’t do any hormone tests before hand, though he did run a PSA and EKG test. And I knew my TT level was likely low normal ~ 376 ng/dl from a test I had done a few years ago. Sure, I know it can change, but it didn’t feel like it changed. After that I pretty much went my own way.

BTW, I had contracted Defy and your intake specialist also repeated the need for the sensitive E2 test giving the same reasons as you stated.

I don’t have a problem with getting the panel Defy needs, and I have never measured IGF-1, so that at least would be new information for me. The rest of the panel, I could pretty much predict what it will indicate. But I have recently been taking Boron, it is reported to raise free T by 28% by lowing SHBG. In the past my SHBG ranged from 37-42 nmol/L. Any significant change in those two measurements I would attribute to the boron supplement. Though it’s not going to be enough of a change to bring me up to the level I would like to be at.

I have learned something new about the E2 standard Vs sensitive test. I had thought sensitive meant the test would measure lower levels of E2 than the standard, but I didn’t know the standard test was error prone.

BTW, I didn’t order the E2 test, an urologist I went to for a prostate exam and to request TRT for me ordered the test. His feelings were that the Low level of E2 was not clinically significant, the low level of free T he ignored and went by the level of Total T as being within normal limits. Talking to his nurse I disagreed, he then wanted to order another test that would include SHBG. I haven’t done the test as I assume it wouldn’t change his mind. And likely my insurance which is Medicare wouldn’t pay for TRT and for the same reason, so I lost interest in that route. He said he wasn't a numbers guy, my first hint that he was a numbers guy, so he would probably be difficult to deal with in any case.


(Honestly, bottom line is that everyone is a numbers guy, just some are more flexible about the numbers.)


In order to get Medicare to pay for TRT, I would probably have to get my TT down to 264.0 ng/dl, which would be nearly impossible to achieve without some sort of drug. So I also have abandoned the idea that maybe Medicare would pay for it.

After reading “Challenges to the Measurement of Estradiol: An Endocrine Society Position Statement”, I can see why this is the case.

https://academic.oup.com/jcem/article/98/4/1376/2536715

 

[Vince Carter]

My Estradiol measured less than 5 pg/ml on the standard test (Roche ECLIA) with a range of 7.6-42.6. Since my estradial is already too low, what is the point of finding out exactly how low it actually is?

How low? Not in every case is LC/MS/MS going to be lower it's a typical kind of loose rule if you will that the Sensitive will read lower than standard. However, when I test and I pull standard and LC/MS/MS on the same blood draw and my sensitive is ALWAYS HIGHER than the standard. I'm an oddball like that.

 

[Vince Carter]

I agree with you that the LC-MS/MS method is more accurate, and especially so for lower levels of E2. Though in my case it's a moot point.

Partly I asked the question because I was wondering if there any value to knowing if my E2 was 2 pg/ml or 4 pg/ml or even 10 pg/ml?

I don't see any value to knowing that, and the only reason at this time I wanted to know was intellectual curiosity.

Moot point because I do not have any exogenous testosterone in my system, and my free testosterone measured 5.5 pg/ml (Roche ECLIA methodology) and my TT was 390 ng/dl (LC/MS-MS method). Which would explain my low E2. (LH 3.6 mIU/mL)

If I were ordering testosterone independent of a doctor/clinic I would do so based on the evidence I have right now. But I already know my medical history for the past 8 years, while a doctor tends to treat a new patient as if they were a newly created human. Meaning they want to start from ground zero.

My reason for getting on this forum was to determine the best method to restart TRT. I had previously been on Nebido for 5 years, but it was mostly independent of a doctor. A doctor in Asia gave me my first injection, he didn't do any hormone tests before hand, though he did run a PSA and EKG test. And I knew my TT level was likely low normal ~ 376 ng/dl from a test I had done a few years ago. Sure, I know it can change, but it didn't feel like it changed. After that I pretty much went my own way.

BTW, I had contracted Defy and your intake specialist also repeated the need for the sensitive E2 test giving the same reasons as you stated.

I don't have a problem with getting the panel Defy needs, and I have never measured IGF-1, so that at least would be new information for me. The rest of the panel, I could pretty much predict what it will indicate. But I have recently been taking Boron, it is reported to raise free T by 28% by lowing SHBG. In the past my SHBG ranged from 37-42 nmol/L. Any significant change in those two measurements I would attribute to the boron supplement. Though it's not going to be enough of a change to bring me up to the level I would like to be at.

I have learned something new about the E2 standard Vs sensitive test. I had thought sensitive meant the test would measure lower levels of E2 than the standard, but I didn't know the standard test was error prone.

BTW, I didn't order the E2 test, an urologist I went to for a prostate exam and to request TRT for me ordered the test. His feelings were that the Low level of E2 was not clinically significant, the low level of free T he ignored and went by the level of Total T as being within normal limits. Talking to his nurse I disagreed, he then wanted to order another test that would include SHBG. I haven't done the test as I assume it wouldn't change his mind. And likely my insurance which is Medicare wouldn't pay for TRT and for the same reason, so I lost interest in that route. He said he wasn't a numbers guy, my first hint that he was a numbers guy, so he would probably be difficult to deal with in any case.


(Honestly, bottom line is that everyone is a numbers guy, just some are more flexible about the numbers.)


In order to get Medicare to pay for TRT, I would probably have to get my TT down to 264.0 ng/dl, which would be nearly impossible to achieve without some sort of drug. So I also have abandoned the idea that maybe Medicare would pay for it.

After reading “Challenges to the Measurement of Estradiol: An Endocrine Society Position Statement”, I can see why this is the case.

https://academic.oup.com/jcem/article/98/4/1376/2536715

no matter how you spin it Standard is the wrong test....Im not sure with that wall of text what you're actually after.

 

[DragonBits]

Vince, I wasn't trying to spin it. The only thing I was wondering was, if your E2 is below 5 pg/m, does it matter how low? So far, no one has said if it matters.


I do think it's odd that life extension specifically disagrees and recommends most people get the standard E2 test. I would opt for the sensitive test even before I read the reasons on this forum.

 

[johndoesmith]

Vince, I wasn't trying to spin it. The only thing I was wondering was, if your E2 is below 5 pg/m, does it matter how low? So far, no one has said if it matters.


I do think it's odd that life extension specifically disagrees and recommends most people get the standard E2 test. I would opt for the sensitive test even before I read the reasons on this forum.

I believe you're looking at this wrong, by asking if knowing how low your E2 actually is matters. As has been stated(by you as well), it may end up that a sensitive test reads higher than the standard, in which case that is critical information to have.

I've often believed I could predict my lab results, and just the other day I had some ran, and was completely wrong. I've been on TRT for a bit now, and have been told I'm rather knowledgeable on the subject(such as by Dr. Saya and Nelson Vergel, as well as other knowledgeable members on this forum). We often get hyper focused on our own cases and cannot see them as clearly as we can see another person's case.

Also, Life Extension is just plain wrong on the Immunoassay being the same as the LC/MS-MS test.

 

[DragonBits]

I believe you're looking at this wrong, by asking if knowing how low your E2 actually is matters. As has been stated(by you as well), it may end up that a sensitive test reads higher than the standard, in which case that is critical information to have.

I've often believed I could predict my lab results, and just the other day I had some ran, and was completely wrong. I've been on TRT for a bit now, and have been told I'm rather knowledgeable on the subject(such as by Dr. Saya and Nelson Vergel, as well as other knowledgeable members on this forum). We often get hyper focused on our own cases and cannot see them as clearly as we can see another person's case.

Also, Life Extension is just plain wrong on the Immunoassay being the same as the LC/MS-MS test.

From the LEF site:
“The LC-MS estradiol test is primarily suggested for situations with very low estrogen levels. It can also be used to monitor E2 levels in both men and woman and may be more accurate compared to immunoassays of estradiol; however, Life Extension® has found the majority of customers do not need this more costly test to get adequate information from the regular immunoassay estradiol test.”

LEF doesn’t say they are the same, only that MOST people get ADEQUATE information from the standard test.

What I really HATE is the loose wording most companies use on their documentation. What is LOW ESTROGEN? What is MOST? What is ADEQUATE?

This isn’t just LEF, it’s widespread everywhere. Because it’s far easier to write LOW rather than give an actual pg/mL level that DEFINES low estrogen.

When I was more naïve, I thought the sensitive test would be able to give me information about estrogen levels below 5 pg/mL.

Not what they mean at all, all test Labs use similar loose wording (not just LEF) and LOW is below somewhere around 35.0 pg/ml, which would be many if not the bulk of men.

So, the sensitive test is more ACCURATE probably for the majority of men.

Standard E2test range 7.6-42.6 (For men)
Sensitive E2 test range 8.0 - 35.0 (for men)

If E2 was close to zero, it would be possible I have an aromatase deficiency, though I doubt it because my E2 was 27.6 pg/ml when I was taking Clomid.

When I do get the sensitive E2 test, several months will have passed, I won’t be able to compare the two tests, but assuming my FT is about the same, I would expect my E2 is about the same. I will be pleasantly surprised if either FT or E2 is higher.

Once you start exogenous testosterone (TRT) I would expect many hormone levels will be moving around in somewhat unpredictable ways and timeframes. For instance. SHBG not only binds with testosterone, it also binds with estrogen. So, I guess lower SGBG levels should mean higher estrogen and higher FT. There are so many feedback loops it seems to me it will take a while to regain a new balance under TRT. I am guessing a while means 1-2 years.

BTW, I am not taking a side here, just chatting about the complexity of hormones in general. I am in favor of getting more accurate information and the sensitive test.

 

[Vince]

From the LEF site:
“Life Extension® has found the majority of customers do not need this more costly test to get adequate information from the regular immunoassay estradiol test.”

They're definitely wrong. They need to do more research.

 

[johndoesmith]

From the LEF site:
“The LC-MS estradiol test is primarily suggested for situations with very low estrogen levels. It can also be used to monitor E2 levels in both men and woman and may be more accurate compared to immunoassays of estradiol; however, Life Extension® has found the majority of customers do not need this more costly test to get adequate information from the regular immunoassay estradiol test.”

LEF doesn’t say they are the same, only that MOST people get ADEQUATE information from the standard test.

What I really HATE is the loose wording most companies use on their documentation. What is LOW ESTROGEN? What is MOST? What is ADEQUATE?

This isn’t just LEF, it’s widespread everywhere. Because it’s far easier to write LOW rather than give an actual pg/mL level that DEFINES low estrogen.

When I was more naïve, I thought the sensitive test would be able to give me information about estrogen levels below 5 pg/mL.

Not what they mean at all, all test Labs use similar loose wording (not just LEF) and LOW is below somewhere around 35.0 pg/ml, which would be many if not the bulk of men.

So, the sensitive test is more ACCURATE probably for the majority of men.

Standard E2test range 7.6-42.6 (For men)
Sensitive E2 test range 8.0 - 35.0 (for men)

If E2 was close to zero, it would be possible I have an aromatase deficiency, though I doubt it because my E2 was 27.6 pg/ml when I was taking Clomid.

When I do get the sensitive E2 test, several months will have passed, I won’t be able to compare the two tests, but assuming my FT is about the same, I would expect my E2 is about the same. I will be pleasantly surprised if either FT or E2 is higher.

Once you start exogenous testosterone (TRT) I would expect many hormone levels will be moving around in somewhat unpredictable ways and timeframes. For instance. SHBG not only binds with testosterone, it also binds with estrogen. So, I guess lower SGBG levels should mean higher estrogen and higher FT. There are so many feedback loops it seems to me it will take a while to regain a new balance under TRT. I am guessing a while means 1-2 years.

BTW, I am not taking a side here, just chatting about the complexity of hormones in general. I am in favor of getting more accurate information and the sensitive test.

Don't have the time to reply fully, but you'd be one of a handful of men to have an aromatase deficiency, and usually it's very obvious.

Not sure what the LEFs hard stance against the sensitive test is, they sell labs, they should give options for people to buy labs, not get unwanted opinions.

 

[viktor]

no entiendo cuales serian los niveles hormonales optimos _?

 

[Nelson Vergel]

Finally, a study comparing the regular versus sensitive estradiol tests.

Study: Comparison of total estradiol measured by immunoassay and LC-MS/MS (sensitive)

Of the subjects, 60 men had total estradiol measured by both the assays. The mean and median total estradiol concentrations measured by immunoassay were 3.95 ± 1.31 and 3.9 [3.1–4.8] ng/dL, respectively. In contrast, the mean and median total estradiol concentrations measured by LC-MS/MS were lower by almost half (2.16 ± 1.66 and 1.9 [0.8–3.2] ng/dL, respectively; P < 0.001 for comparison with immunoassay). The total estradiol concentrations measured by the two assays correlated only weakly (r = 0.37, P = 0.004).
Reference

 

[Valene]

What a huge difference since if you assumed the non-sensitive test was correct, you'd increase the dosage of an aromatase inhibitor, which in this case would put you in jeopardy of osteoporosis (or other medical conditions, since the estradiol is less than 10 pg/ml) if used long-term.

 

[Cataceous]

This thread might be summarized as follows: Estradiol testing via immunoassays cannot be trusted because of the possibility of significant systematic errors. However, what's neglected is that mass spectrometry—sensitive—testing cannot be trusted either, because of the possibility of significant random errors from poor technique.

For me the standard estradiol test is more reliable, period. But I had to first calibrate it against the sensitive test to demonstrate a consistent and relatively small systematic error.

 

[Vince Carter]

This thread might be summarized as follows: Estradiol testing via immunoassays cannot be trusted because of the possibility of significant systematic errors. However, what's neglected is that mass spectrometry—sensitive—testing cannot be trusted either, because of the possibility of significant random errors from poor technique.

For me the standard estradiol test is more reliable, period. But I had to first calibrate it against the sensitive test to demonstrate a consistent and relatively small systematic error.

You had a series of poor LC/MS/MS tests that you were able to prove, right?

 

[Cataceous]

You had a series of poor LC/MS/MS tests that you were able to prove, right?

Yes, and it's buttressed by the comments of others on the pitfalls of MS:

It needs to be noted that mass spectrometry assays are highly complex and require both a high degree of manual adjustments and controlling of operational conditions. Therefore, a high level of skill and knowledge is required to properly set up and operate these methods. Inappropriately operated mass spectrometry methods can lead to profoundly incorrect and inconsistent results. To facilitate the implementation of mass spectrometry in the clinical laboratory, the Clinical and Laboratory Standards Institute (www.CLSI.org) is developing a series of guidance documents, with one specifically addressing methods for steroid hormones. Furthermore, organizations such as the American Association of Clinical Chemistry (www.AACC.org) are offering training opportunities on mass spectrometry for the clinical laboratory.

This comment was made at least four years ago, so you might think the situation would be improving. But one of my botched sensitive tests was just last December.

 

[Cataceous]

This post by "oldolylifter" is excellent and worth including in its entirety:

This is what I believe, based on a little research, regarding the IA v LC/MS/MS issue:

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.

 

[Vince Carter]

So you saw a test or tests of yours that was inexplicably high or low? Because I've seen that in my own tests, part of why I run three tests, LC/MS/MS, ECLIA, and Free Estrogen, to try and have side-by-side comparisons.