clear0cn
Member
@Tyler81 i'm just curious how your experiment turned out?
MESO-Rx
Anabolic Steroids
Steps I am taking to raise my SHBG.
- Thread starter Tyler81
- Start date
I am too, although the low fat part doesn't make sense. Hopefully he corrected that.
Tyler may have been influenced a member of a different forum who successfully doubled his SHBG with most of the methods above.
However, I have seen identical results with berberine alone.
There are a few adjustments I'd make to this regimen. I'll get to those shortly.
Hopefully, Tyler will respond with his results.
However, I have seen identical results with berberine alone.
There are a few adjustments I'd make to this regimen. I'll get to those shortly.
Hopefully, Tyler will respond with his results.
Personally I wouldn't touch metformin with a ten foot barge pole if it raised my SHBG but he obviously has sensible motivations.
Why is that?
The higher the shbg the less test that is available for muscle building purposes.
This is an oversimplification.
In the eugonadal male, elevated SHBG, if it exceeds endogenous steroid production, will limit the free diffusion of steroid hormones through biomembranes.
However, SHBG and testosterone level are positively correlated in healthy men. The more SHBG expressed by the liver, the higher the level of sustainable serum testosterone before steroid metabolism accelerates. SHBG elevation does not reduce FT in healthy men, unless SHBG production is excessive enough that adaption cannot occur.
In contrast, deficient SHBG will not increase androgenic signalling. In healthy men, low SHBG levels will cause early hypothalamic feedback due to elevated free androgen and estrogen until homeostasis is reached and free testosterone level returns to baseline 2-3%. It will not increase free testosterone.
In men on TRT, low SHBG will increase free diffusion through cell membranes, but accelerate hepatic metabolic clearance and reduce intracellular and extracellular AR signalling. In one study, for example, human androgen dependent prostate cancer cells respond to SHBG+T better than they do to pure free T. Why? SHBG is brought into a cell via the extracellular megalin receptor, where it is used to prolong the activity of steroid molecules within a cell. Without SHBG, free testosterone is rapidly glucuronidated and effluxed from the cell. SHBG and T work in concert.
The literature provides us with a case of a totally SHBG deficient male. His complaints were low libido and low musculature, even though he was otherwise fully androgenized. These complaints were not remedied with testosterone supplementation. The study authors concluded that a tissue dependent effect of SHBG on androgenic signalling was proven.
Moreover, there is an extracellular receptor for SHBG that requires SHBG to be unoccupied by a hormone to bind. Once bound, it catches a free steroid molecule and completes the extracellular AR signalling pathway. If SHBG is low, this activity can be nearly completely inhibited.
One interesting thing to note is that on a protien-per-molecule level, SHBG and testosterone are produced in nearly identical quantities. The molecular weights of testosterone versus SHBG are very different, but by serum concentration, a healthy male produces slightly more SHBG than he does testosterone. This is actually required for proper hormone balance and function.
There are no studies that show an independent effect of free testosterone elevation on musculature. This is pure conjecture based on ill-informed "broscience" mythology. In all studies where testosterone positively correlates with lean tissue growth, total testosterone is increased proportionately to SHBG and FT% is within the normal range.
If we look for a case of testosterone administration with low SHBG and a therefore excessively free testosterone percentage, and expect to see better "results in the gym" -- we will not. We have not.
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All that sounds great but overlooks the HIGH affinity SHBG has for TT.
The net effect being, TT offloading from SHBG is minimal until near sub-physiologic levels are reached.
Bottom line changes in SHBG are very unlikely to have a significant impact on anabolic processes.
JIM
The net effect being, TT offloading from SHBG is minimal until near sub-physiologic levels are reached.
Bottom line changes in SHBG are very unlikely to have a significant impact on anabolic processes.
JIM
Wow. Thanks for the write up.
clear0cn
Member
Is this why men on trt with low SHGB need more frequent dosage to feel good?
This is a classic horse before the carriage argument and implies SHBG is directly responsible for anabolic processes.
And while SHBG seems to play
some role, SKM anabolism is a function of TT, and the interaction of other intracellular androgens.
And these androgens are maintained in a diffusable free form outside the cell bc of their loose attachment to ALBUMIN.
I’d be wary. James has a history of posting unsupported theories regarding SHBG. Dr. Scally and Jim had a field day with the theories
I just finished reading your replies to his posts. All very interesting.
Define “liver problems”?
I will tell you I’ve seen a number of folk who ARE hypogonadal and not one improved bc of an independent increase or decrease in SHBG!
And the micromanagement many lament are an effective means of manipulating SHBG are not evidence based, esp from a therapeutic perspective
IME a large portion of these SHBG folk are in search of a physiologic explanation for a psycho-social problem, from obesity to anxiety and depression.
Jim
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Unsupported theories? There is a CASE STUDY in the literature of a low/no SHBG male. The effect is low musculature -- low libido.
For starters, TRT with low SHBG sets an extremely low bar for tolerable total testosterone levels before excessive aromatization becomes a problem.
I am quite irritated by your inability to follow the actual conversation. This thread about normalizing deficient SHBG -- not attempting to alter it in isolation.
Deficient SHBG leads to:
1. Accelerated hepatic metabolic clearance of testosterone. As SHBG decreases, MCR increases. As levels decline beneath the lower end of the physiological range, the MCR becomes exponential rather than linear. However, the MCR of estradiol is relatively unaffected by SHBG alterations. Therefore, estrogen is excreted at a much slower rate than testosterone.
2. Excessive free estradiol. SHBG binds estradiol, and due to the lower affinity of SHBG for estradiol versus DHT or testosterone, the free-to-bound ratio of estradiol is the one most affected by low SHBG.
3. Excessive free testosterone. The primary side effect of excessive free testosterone is elevated estradiol. See #2., where this excessive increase in estradiol also circulates in an excessively free state.
For this reason, all reputable clinics (Defy, Dr. Crisler) treat low SHBG patients differently than those with normal SHBG. The current standard of care for impaired SHBG production is twice weekly to daily injections of testosterone. This is the only way that practitioners have found to minimize the free hormone excess from low SHBG. Don't take it from me, though. Call up any of these clinics and ask them yourself. If you instead favor poorly typed broscience and mythology, check out our resident Dr. ALLCAPS (a.k.a. Dr. JIM.)
Finally, you could do yourself the favor of reading the more recent SHBG related studies. It is no longer considered "just a binding protien." We have learned that it plays a direct role in C-AMP signalling and AR signalling.
If there's something you don't believe, just ask me for the study. Don't just shotgun me with an insufferable rants of disjointed soundbytes loosely related to the topic at hand.
As far as psycho-social problems go, the primary concern for low SHBG men is estradiol issues. The anxiety, depression and obesity that you've mentioned are symptoms of hypogonadism, and it is widely known than men with low SHBG often have poor to no response to TRT. You can search Reddit, if you like. See hundreds of low SHBG threads.
You seem to like to conflate these problems with low SHBG, when in fact they are problems with hypogonadism, and hypogonadism is not easily cured in a case of low SHBG due to a lack of hormonal balance.
Are you a fan of Dr. John Crisler? Most of the Internet is. A favorite quote of mine: "SHBG is the centerpiece of TRT." Google it. Learn from real doctors.
How about a case of increased SHBG increasing response to TRT? Yes, we do have one!
I can introduce you to a fellow with a lifetime SHBG of 14 nmol/L with a poor response to TRT. Following berberine administration for 65 days, his SHBG jumped to 28 nmol/L. This resulted in a massive decrease in estradiol, from 56 pg/mL to 22 pg/mL, with a minimal decrease in total testosterone from 822 to 706 ng/dL. His FT% dropped from 3.63% to 2.65%. He no longer needs anti-estrogens. He no longer needs to divide his dose throughout the week and can now take a single weekly dose like a normal man. If you like, Dr. JIM, I can give you his contact details and you can learn a little more about your craft.
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No. Let's get some facts straight.
Free testosterone diffuses through cell membranes. You've got this part right. Whew! Did you go to medical school? It shows. Here's the part you slept through, though:
Free testosterone that diffuses through cell membranes is rapidly glucuronidated and effluxed. (Translation for Dr. DIM: it bangs around for a little while and then gets inactivated.) Free SHBG is brought into a cell via the Megalin receptor. Intracellular SHBG prolongs the action of testosterone within the cell and is required for normalized AR signalling and to prolong the life of intracellular testosterone.
See:
Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism
"These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease.
In the presence of SHBG, while there is reduced Te uptake, glucuronidation and efflux of Te are also reduced and the effects of Te on androgen responsive genes are enhanced."
Also of note, and to back up my previous post:
"SHBG participates in signaling by first binding to its receptor (RSHBG) on selected cell membranes. After this occurs, the binding to SHBG of an agonist steroid stimulates the rapid production of cAMP. "
"... the receptor-mediated action of SHBG, which uses as a second messenger cAMP, has been linked to the effects of androgens and estradiol. The SHBG/SHBG-R system works as an additional control mechanism which inhibits or amplifies the effects of DHT and estradiol in cells."
"SHBG also functions as part of a novel steroid-signaling
system that is independent of the classical intracellular
steroid receptors. Unlike the intracellular steroid receptors
that are ligand-activated transcription factors, SHBG
mediates androgen and estrogen signaling at the cell
membrane by way of cAMP."
I eagerly await your attempt to save face.
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Dr. Scally is not only now in agreement with me, he has also been posting SHBG related studies into one of my threads, wherein the role of SHBG is expanded upon.
Dr. Crisler recently authored a blog post entitled "How SHBG Really Works," where he concludes, "This is why SHBG is the centerpiece of every proper sex hormone evaluation. It's level dramatically affects not only the patient's response, but what TRT regimen is likely to work the best."
Dr. JIM is the last man standing, cracking his textbooks from 1970 open to look up vocabulary words as he struggles to follow the conversation.
If you want to do interesting reading, just Google around. Dr. JIM is the equivalent of a flat earther, and he is the only one left to debate the long-dead issue.
Lol I love omit when ignorant fools attempt to interpret physiologic processes.
Have you ANY idea where glucoronidatiion occurs, hint a lot of drugs “bang around there”.
You like many others on PED forums see what they want to
and remove “excerpts” from the literature to support bro bullshit.
LMAO.
