Any new discoveries on Low SHBG curse ?

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... I’m 55, lean, very active cyclist, still beating guys half my age.
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Greetings from a fellow cyclist. Good to hear you're doing well. Good info in your post except for the myth about low SHBG leading one to "piss out most of the testosterone you inject, it passes quickly through your system." If you and your normal-SHBG twin are each injecting 70 mg TC per week then you are both metabolizing and excreting the same amount. The rate for both you and your twin is determined by the absorption rate of the testosterone depots, which is unaffected by SHBG. Free testosterone is the same for each twin. If there's a grain of truth in the myth, it lies in the speculation that low SHBG leads to faster intracellular metabolism of testosterone; a shorter residence time for unmetabolized testosterone in that environment would mean that less testosterone is put to work doing useful things.
 
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Disagree. Unless you have a norm shbg vs low shbg trt study to cite than your basic assumptions are incorrect. There are many more factors that affect metabolic rates per individual & low shbg is one of them. The low shbg guy will metabolize the testosterone faster & excrete through urine.
 
Disagree. Unless you have a norm shbg vs low shbg trt study to cite than your basic assumptions are incorrect. There are many more factors that affect metabolic rates per individual & low shbg is one of them.
When I started TRT at 200 mg every 3 weeks, middle of the second week I was still midrange, so this claim that low SHBG men excrete T faster through urination doesn’t hold up. My Total T was 1200 ng/dL 3 days after my injection, with an SHBG of 11.

The low shbg guy will metabolize the testosterone faster & excrete through urine.
Do you have a study to support this claim, that low SHBG men excrete T faster through urination.
 
Disagree. Unless you have a norm shbg vs low shbg trt study to cite than your basic assumptions are incorrect. There are many more factors that affect metabolic rates per individual & low shbg is one of them. The low shbg guy will metabolize the testosterone faster & excrete through urine.
Please be more specific about your claim. Are you saying that free testosterone drops faster in the low SHBG twin? Definitely false. The free testosterone profiles are basically the same. The reasoning is outlined in this post. There's also a sponge analogy for SHBG that may aid in visualization. The limiting factor on the overall rate of metabolism of testosterone is the rate of production/introduction; you can't metabolize testosterone that you don't have yet. Feel free to point out any flaws in the reasoning.

The myth you are defending most likely stems from the fact that if total testosterone is somehow kept constant then a reduction in SHBG does lead to an increase in free testosterone, which would in turn mean faster metabolization and excretion. But as I've pointed out before, this is not a physiological situation. In normal men the HPTA is regulating according to free testosterone, not total. And in men on TRT, free testosterone must be driven in direct proportion to the dose rate to satisfy the law of mass action. In the new paradigm one must think of total testosterone as being a function of free testosterone, SHBG and albumin.
 
You can try taking a high quality DIM supplement. See here: A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen

The takeaway: Serum SHBG also increased with DIM as compared to placebo (+ 25±22 and +1.1 ±19 nmol/L, respectively

Although we're not breast cancer patients taking tamoxifen, taking 150 mg DIM/day definitely increases my SHBG by 5-10.

My theory is that DIM can also acts as a weak AI - there's some stuff out there that says otherwise, but, if DIM raises SHBG, you would expect total E2 levels to increase absent any other effects. Thus if SHBG is raised, and total E2 levels stay the same, or even increase to a lesser extent than expected by the raise in SHBG - DIM can be lowering free E2 levels.
 
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My theory is that DIM can also acts as a weak AI - there's some stuff out there that says otherwise, but, if DIM raises SHBG, you would expect total E2 levels to increase absent any other effects. Thus if SHBG is raised, and total E2 levels stay the same, or even increase to a lesser extent than expected by the raise in SHBG - DIM can be lowering free E2 levels.
Isn't an AI expected to lower SHBG because of the increase in testosterone and decrease in estradiol? Perhaps DIM's estrogenic effects are responsible for the rise in SHBG.

A separate study shows that DIM's estrogenic effects can be mediated through ERβ but not ERα activation of estrogen response element and DIM selectively activated multiple endogenous genes through ERβ[40]. The possible mechanisms by which DIM induces these effects do not involve binding to ERβ but may involve a ligand-independent mechanism by recruiting coactivators to target genes[40]. It was reported that induction of p21 expression by DIM was independent of estrogen-receptor signaling[21].
[R]
 
Isn't an AI expected to lower SHBG because of the increase in testosterone and decrease in estradiol? Perhaps DIM's estrogenic effects are responsible for the rise in SHBG.

A separate study shows that DIM's estrogenic effects can be mediated through ERβ but not ERα activation of estrogen response element and DIM selectively activated multiple endogenous genes through ERβ[40]. The possible mechanisms by which DIM induces these effects do not involve binding to ERβ but may involve a ligand-independent mechanism by recruiting coactivators to target genes[40]. It was reported that induction of p21 expression by DIM was independent of estrogen-receptor signaling[21].
[R]
To be clear I have no science behind DIM acting as an AI lol - just a general trend from my (n=1) labs that DIM significantly raises my SHBG while seeming to not effect total E2. I used to have a bunch of bookmarks on SHBG metabolism and was going to make a post here about 6 months ago for the low SHBG guys, but I've had some other health issues, stopped taking DIM, and got a new computer and lost most of those bookmarks. Oops

As far as SHBG - my question boils down to how exactly is DIM raising SHBG? Like as in your link we know DIM can have estrogenic effects - but if DIM was so powerfully acting as an estrogen, enough to significantly increase SHBG, wouldn't people notice those effects while taking it? I mean, how much would you have to increase your E2 levels to increase SHBG by 10 units? I'm guessing enough that you'd notice some negative effects.

Low SHBG is negatively associated with a lot of health issues - for instance, insulin resistance and obesity can lower SHBG, but it appears to be a positive feedback loop - insulin sensitivity lowers SHBG, which lowers insulin sensitivity, etc. etc.

Your link shows DIM activating ERβ, but not ERα. My original thought was that perhaps the liver, where SHBG is mainly produced, has an extremely high density of ERβ, and very little ERα. Now read this link:
Estrogen Receptor beta (ERβ) Regulation of Lipid Homeostasis—Does Sex Matter

Some outtakes:
E2 treatment reduces adiposity in both sexes and improves metabolic adaptation to obesity through the activation of both ERs [3,4]. However, it also mediates cell proliferation through activation of ERα present in target tissues and can thus contribute to malignant growth in these tissues. These detrimental effects render the use of E2- and/or ERα-selective agonists as a treatment for obesity difficult, whereas ERβ is thought to counteract these activities [5]. Recently, selective activation of ERβ has demonstrated beneficial outcomes on metabolic control in obesity [6,7,8,9], probably through feedback mechanisms, since ERβ is expressed at very low levels in metabolic tissues including the liver.
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Indeed, liver cells express very little the ERβ subtype compared to ERα; therefore, the effects observed by the activation of ERβ by a ligand might result from a feedback loop or crosstalk from other tissues.
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More recently, extensive research has demonstrated beneficial metabolic outcomes of ERβ activation and has defined a central role for ERβ in metabolic control. However, further research is needed to elucidate the role of ERβ in lipid homeostasis. Targeting ERβ in order to tackle metabolic disorders associated with obesity without inducing the side effects of ERα activation could be a potential solution


It appears to be the opposite of my original theory - the liver has relatively little ERb compared to ERa. However, "Targeting ERβ in order to tackle metabolic disorders associated with obesity without inducing the side effects of ERα activation" isn't this exactly what DIM does? And is it possible that some of these benefits are due to an increase in SHBG?

As far as DIM acting as an AI - I really wish we had a relatively accurate "Free E2" calculator, like we do with Free Testosterone. That way we could see how much you would expect Total E2 to raise, given an increase in SHBG.
 
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As far as DIM acting as an AI - I really wish we had a relatively accurate "Free E2" calculator, like we do with Free Testosterone. That way we could see how much you would expect Total E2 to raise, given an increase in SHBG.
This free E2 calculator seems to be pretty decent. See what kind of numbers you get.

By the way, were you at PeakT under the same user name? If so you had some interesting posts there, and I've mentioned a couple of them over here.
 
my SHBG is 11. i am on 210mg T weekly. i feel great. libido through the roof. 0 symptoms from SHBG as far as i can tell. you have no clue if your symptoms are shgb related and most likely they are not
My SHGB is like yours. I struggle to get things right. Currently I'm doing around 180mg weekly. Curious if you inject daily?
 
Disagree. Unless you have a norm shbg vs low shbg trt study to cite than your basic assumptions are incorrect. There are many more factors that affect metabolic rates per individual & low shbg is one of them. The low shbg guy will metabolize the testosterone faster & excrete through urine.
Which test ester are you using? :)
 
I m just checking with the community to see if there is a new discovery with Low SHBG individuals ?
Any new treatment ?
Any new strategies to raise it ?

It is a bad curse .
I recommend booking/paying for a consult with Dr. Andrew Winge. It will be the best $300 you spent. He'll go over EVERYTHING from labs to your protocol to advising on SHBG specific to YOU. He is a very honest guy and knows every medical nuance of TRT. He's an active ER physician right now and runs a men's clinic on the side.

He is, from experience, the best TRT doc in the USA, knows absolutely everything inside and out not just from testosterone but related medicine too. See his YouTube channel ManMedicine. My SHBG is single digit but I feel good.
 
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What are your complaints ?
I've been on TRT more than 20 years. The best I experienced was the first six months on Androgel. Then I started having absorption issues. I have tried about every delivery method available since then and just don't feel like I get the benefits I should. The SHGB was not even looked at back then. I think the last lab it was in single digits. I'm currently injecting 30mg daily and I can't tell much difference. I have the 200 mg scrotal cream too and I try it occasionally and it does nothing. Libido sucks, stay tired most of the time, etc. I'm getting labs done tomorrow and I would be happy for you to look at them and give me your advice.
 
I've been on TRT more than 20 years. The best I experienced was the first six months on Androgel. Then I started having absorption issues. I have tried about every delivery method available since then and just don't feel like I get the benefits I should. The SHGB was not even looked at back then. I think the last lab it was in single digits. I'm currently injecting 30mg daily and I can't tell much difference. I have the 200 mg scrotal cream too and I try it occasionally and it does nothing. Libido sucks, stay tired most of the time, etc. I'm getting labs done tomorrow and I would be happy for you to look at them and give me your advice.
You should consider Jatenzo, Kyzatrex or Orlando oral testosterone.
 
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I m just checking with the community to see if there is a new discovery with Low SHBG individuals ?
Any new treatment ?
Any new strategies to raise it ?

It is a bad curse .
Been on TRT since 2017. I was a low teens SHBG guy and felt best with daily injections……felt OK but not great. I started a high protein version of the Keto diet October of 22, not to try and raise SHBG, but to attempt to address my pre-diabetic emerging condition. As I became Keto adapted my SHBG raised significantly and has remained there. My last three bloodwork’s were 29, 27, and 28. For over 5 years I was between 11 and 15.
 
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Been on TRT since 2017. I was a low teens SHBG guy and felt best with daily injections……felt OK but not great. I started a high protein version of the Keto diet October of 22, not to try and raise SHBG, but to attempt to address my pre-diabetic emerging condition. As I became Keto adapted my SHBG raised significantly and has remained there. My last three bloodwork’s were 29, 27, and 28. For over 5 years I was between 11 and 15.
But do you feel any different Trt wise ?
 
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