Thanks for taking the time to write this up, I appreciate the explanation.The principle is the same with exogenous testosterone. Instead of internal HPTA regulation of free testosterone there is external regulation via our control of the dose rate. Your example would get complicated if you're talking about injecting pure testosterone and DHT. But typically these hormones are injected as long-acting esters, which lead to a slow and steady introduction of the base hormones into circulation. The DHT does effectively make less SHBG available to bind testosterone. I illustrated above that this does not affect free testosterone when T and DHT are being introduced at constant rates.
Another point about your example is that overall metabolism of testosterone is limited by the rate of production or dosing. If testosterone is slowly being absorbed from a depot then you cannot on average metabolize testosterone at a faster rate than it is coming in. If you provide a sudden spike of pure DHT then you would have a brief surge in free T and its metabolism. But as the DHT declines things go the other way, with a short-lived excess of available SHBG causing free T to fall below baseline. If you take the average of free testosterone over the transient period then you'd find that it's the same as during the original steady state.
Somebody proposed a sponge analogy for SHBG, which is fleshed-out here. I find it useful for getting a sense of SHBG's role as a storage buffer for testosterone. It also highlights that the main action we care about is the "flow" of free testosterone from production/dosing to eventual metabolism and elimination.
First post. Can’t get E2 under control, starting to worry
- Thread starter Stalerigatoni
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Thanks for taking the time to write this up, I appreciate the explanation.
Wow. Totally speaks for itself.
Yet you use those precious few minutes to write abusive drivel? I find it troubling that you are apparently a practicing physician. Pity the poor patient who questions anything you say.
Charliebizz
Well-Known Member
@RobRoy you quoted my post. I am not a super moderator lol. I’m just a regular joe on trt. And actually believes in most of the things you say. No reason to get all crazy. I was just posting my labs to show that when my dht was mid range on injections my free t was the same when my dht was very high on cream.
I was injecting 3x a week at the time I don’t recall when I actually took the labs test. And on cream I was doing 3 clicks am 3 pm.
We all know the type of small business owner who gets agravated when something is questioned.
Robroy uses an analogy of plant watering, the thing is, the thirst that is quenched may vary, all men may not be equal in their saturation point, meaning adverse effects do occur before the receptors in tissues are done taking more in, over simplifying things has a strong appeal.
I don’t get it….why? Why would you feel the need to come on here and rip on someone? I accept the fact you have extensive training and clinical experience, and have probably done good things for many patients. However, to act like ALL of the science is settled in this field and you have ALL of the answers for EVERYONE is a bit smug. Rouzier comes across the same way, so the kool aid must enhance some predisposition to act like an a***ole as part of the package.
Charliebizz
Well-Known Member
Because @RobRoy refuses to answer a few questions and I feel when he feels the heat his default is to lash out. What grown man asks to be banned. I’m not here to talk shit and attack anyone. But I’ve heard my fair share of stories from former patients to know to stay away from his practice. While I believe in much of his theory’s and cream has been a huge win for me. I think he is very unprofessional. I love having him here for civil debate. But grow up.
Seems this statement was around when standard trt was one bolus dose every 2-3 weeks, it seems like weekly injections are the new standard, gel could also be labeled standard trt. The standard would largely depend on the practicioner i guess.
In Europe standard trt is 1ml/250mg injected every two weeks or so sust/enan, or nebido full dose, or gel, you hear the same statement here as well from doctors.
Good points. I thought they meant optimizing T dosing protocol alone works only for ~80%. For the rest they cannot find a "feel good" balance without any ancillary drugs/blood donation.
I think it’s probably accurate….the middle 75-80 percent on the bell curve will probably notice improvements and not have any real side effects with the doctor following the Pfizer instructions or the Endocrine Society recommendations. As I’ve stated, I know SEVERAL guys (as we all probably do) on the standard 1/2 cc or so once a week and they move on with their life and it doesn’t cause any issues….Ive commented before just how jealous that makes me!
I know a lot of men on TRT in real life. And every one takes one shot a week in the ballpark of 100mg and feels great. One guy splits it up into twice a week and that's only because I suggested it because he said he felt tired the last day or two.
They don't even think about it unless it's injection day, and I honestly think that's one of the biggest contributing factors to their success on TRT.
Couldn’t agree more….I ll probably have to start lower (60-70 mg range), but I have not given once a week dosing a fair shot since early on when I was prescribed 200 mg a week. It may be time to do that….
FunkOdyssey
Seeker of Wisdom
By this logic, it is not worth measuring testosterone either, because testosterone does not exert its effects in serum, only in tissues. The fact is, the hormones we are measuring, circulating in serum, make their way into tissues and exert effects there. This is equally true for both testosterone and estradiol, and that is why it is worth measuring and concerning yourself with both hormones.
There is no unidirectional transporter in tissues that only allows E2 produced locally via aromatization to travel out from that tissue to the serum. E2 can just as easily pass from serum INTO tissues and exert effects as an endocrine hormone.
One of the best models in men to prove that is with estradiol administration in the context of androgen deprivation therapy (ADT). In these scenarios, men with prostate cancer are chemically castrated, reducing both T and E2 to nil, and then estradiol is administered to relieve men of some of the negative side effects.
When you restore serum E2 to physiological levels in men on ADT, their markers of bone health improve. Bone resorption is halted and bone density increases. There is no aromatization of testosterone occurring in these men. This is E2 measured in serum, traveling from the serum into the tissue, exerting endocrine effects. The same physiologic serum E2 levels will also relieve vasomotor symptoms like hot flashes in these men.
Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial - PubMed
Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.
pubmed.ncbi.nlm.nih.gov
Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial - PubMed
In men with castrate levels of E2 and TS, daily transdermal E2: 0.9-1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test...
pubmed.ncbi.nlm.nih.gov
What happens when you go beyond physiologic serum E2 levels in men on ADT with estradiol administration? Gynecomastia. You are basically performing a gender transition on them, as the endocrine effects of high serum E2 work their magic in the tissues, in the absence of T and DHT to balance it.
Nipple tenderness was noted in 1 of 12 men receiving 0.9 mg, 2 of 12 men receiving 1.8 mg
and none using placebo gel in this study. In the PATCH trial, 75% of men receiving a high dose transdermal E2 regimen, sufficient to induce castrate T concentrations without GnRH analogs, experienced gynaecomastia compared to 19% of men receiving GnRH analogs (8). It is unknown to what extent long-term low dose transdermal E2 add-back will increase the incidence of breast adverse effects above that caused by GnRH analogs alone.
Basically what the anti-AI crowd has done is taken the nugget of truth that E2 often or even primarily functions as a paracrine hormone in men, and said that is the ONLY conceivable thing happening with E2. We will deny that high serum levels of E2 could ever possibly have undesired endocrine effects. We will bury our heads as far in the sand as necessary, creating carefully policed echo chambers on the Internet, such that we never have to consider that possibility again.
Just because AI's are not a safe and effective solution to undesirable effects of excessive E2 doesn't mean it is impossible for excessive E2 to cause undesirable effects. You've thrown the baby out with the bathwater.
Charliebizz
Well-Known Member
But how does that pertain to trt. If you have high enough e2 to “transition” you would have high enough testosterone on trt for that not to happen lol.By this logic, it is not worth measuring testosterone either, because testosterone does not exert its effects in serum, only in tissues. The fact is, the hormones we are measuring, circulating in serum, make their way into tissues and exert effects there. This is equally true for both testosterone and estradiol, and that is why it is worth measuring and concerning yourself with both hormones.
There is no unidirectional transporter in tissues that only allows E2 produced locally via aromatization to travel out from that tissue to the serum. E2 can just as easily pass from serum INTO tissues and exert effects as an endocrine hormone.
One of the best models in men to prove that is with estradiol administration in the context of androgen deprivation therapy (ADT). In these scenarios, men with prostate cancer are chemically castrated, reducing both T and E2 to nil, and then estradiol is administered to relieve men of some of the negative side effects.
When you restore serum E2 to physiological levels in men on ADT, their markers of bone health improve. Bone resorption is halted and bone density increases. There is no aromatization of testosterone occurring in these men. This is E2 measured in serum, traveling from the serum into the tissue, exerting endocrine effects. The same physiologic serum E2 levels will also relieve vasomotor symptoms like hot flashes in these men.
Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial - PubMed
Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial - PubMed
In men with castrate levels of E2 and TS, daily transdermal E2: 0.9-1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test...
What happens when you go beyond physiologic serum E2 levels in men on ADT with estradiol administration? Gynecomastia. You are basically performing a gender transition on them, as the endocrine effects of high serum E2 work their magic in the tissues, in the absence of T and DHT to balance it.
Nipple tenderness was noted in 1 of 12 men receiving 0.9 mg, 2 of 12 men receiving 1.8 mg
and none using placebo gel in this study. In the PATCH trial, 75% of men receiving a high dose transdermal E2 regimen, sufficient to induce castrate T concentrations without GnRH analogs, experienced gynaecomastia compared to 19% of men receiving GnRH analogs (8). It is unknown to what extent long-term low dose transdermal E2 add-back will increase the incidence of breast adverse effects above that caused by GnRH analogs alone.
Basically what the anti-AI crowd has done is taken the nugget of truth that E2 often or even primarily functions as a paracrine hormone in men, and said that is the ONLY conceivable thing happening with E2. We will deny that high serum levels of E2 could ever possibly have undesired endocrine effects. We will bury our heads as far in the sand as necessary, creating carefully policed echo chambers on the Internet, such that we never have to consider that possibility again.
Just because AI's are not a safe and effective solution to undesirable effects of excessive E2 doesn't mean it is impossible for excessive E2 to cause undesirable effects. You've thrown the baby out with the bathwater.
FunkOdyssey
Seeker of Wisdom
The point is that E2 can act as an endocrine hormone in men, meaning it can be produced in one location, travel through the blood, and exert effects at a distant location. It pertains to TRT because TRT increases your serum E2 and this endocrine form of E2 signaling at the same time, for good, and for ill.
Yes and pretty sure many will notice the adverse effects of added e2 orally or otherwise like myself, the most hardcore antiAI docs out there are bragging on their e2 add ons of course, meanwhile if you take notes, on the hardcore side of "there is no such thing as too high e2" certain behaviour traits seem common.
I was going to post this after a certain reply in this thread but didn't want to stir the pot too much lol
Have you guys seen this research: Controlling the polycythemia effect associated with TRT
I think madman's post of this research hasn't gotten much attention.
Thanks for all the discussions and sharing of experiences. I gave up on optimizing my androgel with ancillaries (hcg, anastrozol, dhea, proviron). Yesterday I started with testosterone undecanoate subq.
I think madman's post of this research hasn't gotten much attention.
Thanks for all the discussions and sharing of experiences. I gave up on optimizing my androgel with ancillaries (hcg, anastrozol, dhea, proviron). Yesterday I started with testosterone undecanoate subq.
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