New hypothesis: Free E2 rant, E2:SHBG ratios, why does no one bother

[bixt]

So this relates to all forums, Reddit, various YouTube videos from doctors, pretty much every internet information source.

As of the past few years all the rage and focus is on FT. So much so that certain tests are referred to with derogatory names. “Piss poor”. That’s how important FT is to everyone is 2023. Years ago it was all about TT. I agree with all of this and it makes total sense.

But what about the OTHER important hormone, E2. Why are we content to measure plain Jane total E2 (analogous to testing TT). Why are we not testing free E2?

I find this highly problematic for many reasons.

It is akin to only using TT for test. We now know it’s the free fraction that’s doing the job which is why FT is so important in 2023. We no longer talk in absolutes and say that for example 600 TT is low, 2000TT is high and 1200TT is where symptom resolution occurs. We say that ft of 10 is low, ft of 25 is good, etc

On the other hand E2 is discussed and measured in absolutes. <20 is low, some people say for example 50 is the upper end, yet others say the sky is the limit.

I find this highly problematic. It is hypocritical that T must be measured by it’s free fraction, yet total E2 and not free E2 is fine.

Lastly no consideration is given to SHBG. The % of E2 which binds with SHBG is different than androgens. Dropping SHBG artificially in a patient taking exogenous T will not equally increase fT and fE2 equally. I will illustrate this below.

Take two hypothetical individuals with a measured gold standard fT of 25 and an E2 of 60. One has a normal SHBG, one has a low SHBG. Forumites will discuss those E2 figures and make comments and give advice on them freely without taking into account the fact that the ratio of free E2 to free T could be vastly different between the two. While both have fT 25 and E2 60, for all I know the low SHBG guy has 3 times the levels of free floating E2 causing havoc.

Coincidently plenty of low SHBG individuals notoriously have strange side effects. Its perhaps from this huge (relative to fT) amount of (unmeasured) free E2 floating around causing shit.

I think it time to consider testing free E2 (if such a thing even exists, I have never seen such bloods posted anywhere), or at the very least consider E2:SHBG ratios when assessing people’s cases.

As to what ideal values for either fE2, fE2:fT or (SHBG:E2):fT would be, I have no idea right now. When the fE2 data trickles in, perhaps years from now, we could crunch the numbers, design protocols on it and maybe dial in by numbers far better than we currently do.

 

[Cataceous]

I agree that free estradiol needs greater emphasis. @Gman86 posted a ton of his free estradiol data in this thread. They seem to correspond well to values calculated using the immunoassay-based total estradiol tests.

Take two hypothetical individuals with a measured gold standard fT of 25 and an E2 of 60. One has a normal SHBG, one has a low SHBG. ...​

I've used these "twin" experiments to illustrate that in individuals who differ only in their SHBG, total testosterone varies in response to SHBG. There is no pressure on free testosterone to change at the new steady state. You are now making the same mistake I did, which is to assume a fixed total estradiol. In fact estradiol is produced from free testosterone, and in proportion. With free levels proportional to the production rate you end up with free estradiol proportional to free testosterone. Therefore, in twins with different SHBG the level of free estradiol is unchanged, while the level of total estradiol is lower in the twin with lower SHBG.

It's true that there are still some subtleties connected to SHBG's role in transporting steroids. I suspect that macroscopically these can be neglected in favor of the law of mass action applied to the free hormone levels. However, they may well be significant in explaining why a twin with low SHBG may not fare as well as a twin with normal SHBG. One hypothesis is that low SHBG impairs androgenic activity more than it does estrogenic activity, even when free hormone levels are the same.

 

[Charliebizz]

I agree that free estradiol needs greater emphasis. @Gman86 posted a ton of his free estradiol data in this thread. They seem to correspond well to values calculated using the immunoassay-based total estradiol tests.

Take two hypothetical individuals with a measured gold standard fT of 25 and an E2 of 60. One has a normal SHBG, one has a low SHBG. ...​

I've used these "twin" experiments to illustrate that in individuals who differ only in their SHBG, total testosterone varies in response to SHBG. There is no pressure on free testosterone to change at the new steady state. You are now making the same mistake I did, which is to assume a fixed total estradiol. In fact estradiol is produced from free testosterone, and in proportion. With free levels proportional to the production rate you end up with free estradiol proportional to free testosterone. Therefore, in twins with different SHBG the level of free estradiol is unchanged, while the level of total estradiol is lower in the twin with lower SHBG.

It's true that there are still some subtleties connected to SHBG's role in transporting steroids. I suspect that macroscopically these can be neglected in favor of the law of mass action applied to the free hormone levels. However, they may well be significant in explaining why a twin with low SHBG may not fare as well as a twin with normal SHBG. One hypothesis is that low SHBG impairs androgenic activity more than it does estrogenic activity, even when free hormone levels are the same.

in many other groups I’m seeing most of the low shbg guys that are doing well are actually taking higher doses of testosterone. This forum seems to have most low shbg guys doing low dose, running lower tt levels and not feeling well. I’m a low shbg guy and been messing around with the cream. I’ve yet to get tested but I’ll tell you this my libido and erections way better the. On injections. I’m assuming my levels are pretty high but we shall see.

 

[Systemlord]

I believe the problem for a lot of low SHBG men isn’t the high normal levels, but the constantly elevated hormones. I couldn’t tolerate anything over 500 ng/dL on injections, however on short acting esters, I can handle 1052 ng/dL no problem!

I feel no different at peak than I do at trough, 1052-300>.

My SHBG was 11 and is hovering around 24 now.

I wonder about the internal conflict in someone with bad case metabolic syndrome, where the TRT is pulling in one direction, while the MBS is pulling in the other direction. This is where I believe some of the symptoms come from in some guys that struggle on TRT.

 

[Charliebizz]

I believe the problem for a lot of low SHBG men isn’t the high normal levels, but the constantly elevated hormones. I couldn’t tolerate anything over 500 ng/dL on injections, however on short acting esters, I can handle 1052 ng/dL no problem!

I feel no different at peak than I do at trough, 1052-300>.

My SHBG was 11 and is hovering around 24 now.

I wonder about the internal conflict in someone with bad case metabolic syndrome, where the TRT is pulling in one direction, while the MBS is pulling in the other direction. This is where I believe some of the symptoms come from in some guys that struggle on TRT.

Maybe something to that. I’ve seen a physician on t-nation who has majority of his men on 1-2x a week injections. good amount with low shbg and he reports they feel great and they all on doses higher then 120 a week. But a lot of them keep the trough high. not really sure what to make of it. But just an observation it seems most low shbg guys I’ve seen doing well keep t levels pretty high.

that said. my levels fluctuate a good amount even on 3x a week injections. I’ve tested a few times Ive dropped as much as 400 pts when testing 8hrs after injection vs 26 hours. And I still dont feel great on injections.

 

[Systemlord]

Maybe something to that. I’ve seen a physician on t-nation who has majority of his men on 1-2x a week injections. good amount with low shbg and he reports they feel great and they all on doses higher then 120 a week. But a lot of them keep the trough high. not really sure what to make of it. But just an observation it seems most low shbg guys I’ve seen doing well keep t levels pretty high.

that said. my levels fluctuate a good amount even on 3x a week injections. I’ve tested a few times Ive dropped as much as 400 pts when testing 8hrs after injection vs 26 hours. And I still dont feel great on injections.

I have heard a doctor on Youtube talk about men with underlining health problems may not tolerate high T very well, at least until they get control of those underlining health issues.

 

[t_spacemonkey]

my SHBG is 11. I run into high e2 side effects at higher T doses, but I don't feel very good below 150mg/week. TBH the best I feel is around 200mg/week. but ironically my total T is around 500ng/dl and free T is around 25 at that level. so where is that T going?
my libido goes up proportionally with a high T dose and energy/mood as well.
but I get weird e2 symptoms as well, mostly mental however, like restlessness which goes away when I take an AI. which also makes me question the anti-AI group a bit.
maybe I am one of the few which will do well with high T/week+small dose AI 1-2x week.
still trying to adjust dosing. my e2 is consistently around 70 or higher

 

[Systemlord]

my libido goes up proportionally with a high T dose and energy/mood as well.
but I get weird e2 symptoms as well, mostly mental however, like restlessness which goes away when I take an AI.

Higher estrogen, you hold onto more water, so maybe it’s not so much the higher estrogen as it is more water in your tissues.

Have you tried dandelion root as a weak diuretic?

 

[Charliebizz]

I have heard a doctor on Youtube talk about men with underlining health problems may not tolerate high T very well, at least until they get control of those underlining health issues.

It’s strange. Trt helps with libido, erections,recovery from workouts and my performance at hockey. Really just my mental well-being started to go down the tubes. I recently started low dose lexapro again (2.5mg) and so far so good. My only real complaint is I’m still so damn tired on trt. i Do have some symptoms of metabolic issues. One being low body temps. My thyroid numbers are good. Ive tried thyroid in the past and didn’t feel any better. All my other “metabolic markers” in labs are great. The only things that stand out are low shbg and my low hdl and high triglycerides. However if I cut carbs they get much better.

 

[Systemlord]

High triglycerides is metabolic syndrome.

 

[Charliebizz]

High triglycerides is metabolic syndrome.

All I have to do is lower my carb intake and they come back well within normal range. I’ve had high triglycerides since I was a kid

 

[Systemlord]

Not all carbs are created equal, cut the bad ones out.

 

[TRicker]

in many other groups I’m seeing most of the low shbg guys that are doing well are actually taking higher doses of testosterone

Do you happen to know if any of the low shbg guys that take higher doses also take an ai? I have low shbg as well, and definitely do better on higher doses. Finding the sweet spot for estrogen is the problem.

 

[Charliebizz]

Do you happen to know if any of the low shbg guys that take higher doses also take an ai? I have low shbg as well, and definitely do better on higher doses. Finding the sweet spot for estrogen is the problem.

Majority no. The one physician on t-nation had a nice spreadsheet of his patients what dose they were on, what t levels, estrogen, shbg, and he said only a hand full of his patients used a.i just because they “believed” they needed it.

I don't want to get into the a.i debate. But me personally I would never touch them. And if I couldn't make trt work without them I would get off trt