With all the emphasis on free T and free t3/t4 these days, why is not important to test free estradiol or free DHT? LabCorp has tests for these but I’ve never seen anyone get them done.
Is there a reason I’m not considering other than it’s just not standard so it’s difficult to compare apples to oranges?
Free estrogen testing is expense, $100> per test. We can’t assume if everyone had an E2 of 25 that free E2 would be the same for everyone, especially men with SHBG <10. The reference ranges are an unknown, so it will be up to you to figure your optimal ranges.
If you find yourself feeling optimal with free E2 on the bottom end of the ranges, you have your optimal range, however if you are at the top end of the ranges and not feeling your best…
When my TT is below midrange 417 ng/dL, my FT is close to the top of the ranges and I’m willing to bet free E2 is as well.
It makes sense people wouldn’t use it if it’s that expensive. I didn’t get that far, I just checked to see if labcorp even had the tests and saw that they did
It also makes sense that there aren’t currently any normal ranges so we’d kind of be getting data and have no idea what it means. But, the same can be said for every test at one point or another. People have to use it for normal ranges to be established and for the community to understand what works and what doesn’t.
It just came across as odd to me how important everyone makes free T sound but no one seems to question why the “free” part doesn’t matter with e2 or dht.
I was also curious if my free e2 was effectively still low somehow because of my high shbg and thought this might be a way to check. I’m certainly not paying $400 to find out what mine is, though.
In physiolojik’s AI thread he goes into some depth about the different estrogens (sub-estrogens?). I remember reading it a year ago but that’s about it. E1, E2 & E3.
The short answer is that it’s technically very difficult to measure free E2 and DHT because
one needs to separate free from bound by dialysis or ultracentrifugation without changing the ratio that is found in serum (but that’s also the problem for free T but itself presents a major challenge)
specifically for free E2 and DHT, their levels in serum are a factor 50 to 500 lower than that of free T. The very low concentration of free E2 and DHT in the range of appr 1 pg/ml makes it very difficult to quantify these analytes with a reasonable accuracy and precision (that’s why the tests are so expensive)
Free E2 and DHT can be estimated from their total concentration and the level of SHBG. Affinity of E2 to SHBG is about 3 fold lower and affinity if DHT to SHBG is about 3 fold higher compared to the affinity of T to SHBG.
Mathematically calculating the free levels of all ligands is challenging. Vermeulen or Anderson use a 1 ligand 2 protein model to calculate free T, basically ignoring the presence of the other ligands which presents a certain limitation of the calculated free T levels (but still good enough for clinical decision making). Calculating the free levels of T, E2 and DHT requires a 3 ligands 2 protein model which makes things much more complicate.
Anyhow Mazer came up with a simple Excel spreadsheet to calculate the free forms. One can download it here (at the end of the article):
Clinically there is now a lot of evidence that free T and the T to E2 ratio are the most important parameters. As the ratio T to E2 is not different from the ratio free T to free E2 there is no added benefit in measuring free E2 given the technically difficult assay.
Thanks for this post @johann77, it’s great. I’m having a hard time finding the spreadsheet. Maybe it’s because I’m on my phone? Where in the article is it again?