TRT in men with low SHBG

[markuspartacus]

SHBG is the main carrier protein for Testosterone, low levels of which will mean that you will have low total testosterone. It also binds estrogen to a lesser extent, however low SHBG levels will also mean you will have higher circulating levels of Estrogen.

The culprit has already been pointed out "insulin"

Get a 12 hour fasting insulin test, Average result for a normal health person should be around 6 to 10 mIU/ml anything above 10 suggests insulin resistance. Most labs will have a range between 2 - 20 mIU/ml for Normal, however they are only looking for abnormalities in the Pancreas such as Insulinomas (Insulin producing Tumours) not for insulin resistance.

There are only a few drugs that will incease SHBG, Diazoxide and Pioglitazone are two of them.

Diazoxide which is used to treat insulinomas lowers the pancreas output of insulin thus increasing SHBG production.

Pioglitazone used to treat Type 2 diabetes reduces insulin resistance and speeds up the removal of insulin thus increasing SHBG.

 

[James23]

Thanks, markuspartacus.

I had a 12 hour fasting insulin test and insulin was <1 mlU/ml.

I think a GTT test (the 3 hour type) is more appropriate.

 

[Wheat Thins]

Low SHBG complicates matters but is not an unsolvable problem in most people.

But in some people it is an unsolvable problem? What happens if someone has an unsolvable problem?

 

[BBC3]

Perhaps there is a relation. But that is far from enough. I have seen enough labs posted around here to know that shbg is a variable as TT levels. no proof. I will say that I have a propensity for type II diabetes, which is why this thread catches my attention. But I have seen nothing to incriminate, just that they corrolate. My insulin levels have been steady 125 under a load since I was 19. This has never changed. SHBG I am sure has. I run 13 on that one with a corresponding high Free T level. How do we know this is not just simply a reflection of fuel delivery to muscle as T relates.......

SHBG is the main carrier protein for Testosterone, low levels of which will mean that you will have low total testosterone. It also binds estrogen to a lesser extent, however low SHBG levels will also mean you will have higher circulating levels of Estrogen.

The culprit has already been pointed out "insulin"

Get a 12 hour fasting insulin test, Average result for a normal health person should be around 6 to 10 mIU/ml anything above 10 suggests insulin resistance. Most labs will have a range between 2 - 20 mIU/ml for Normal, however they are only looking for abnormalities in the Pancreas such as Insulinomas (Insulin producing Tumours) not for insulin resistance.

There are only a few drugs that will incease SHBG, Diazoxide and Pioglitazone are two of them.

Diazoxide which is used to treat insulinomas lowers the pancreas output of insulin thus increasing SHBG production.

Pioglitazone used to treat Type 2 diabetes reduces insulin resistance and speeds up the removal of insulin thus increasing SHBG.

 

[BBC3]

Perhaps there is a relation. But that is far from enough. I have seen enough labs posted around here to know that shbg is a variable as TT levels. no proof. I will say that I have a propensity for type II diabetes, which is why this thread catches my attention. But I have seen nothing to incriminate, just that they corrolate. My insulin levels have been steady 125 under a load since I was 19. This has never changed. SHBG I am sure has. I run 13 on that one with a corresponding high Free T level. How do we know this is not just simply a reflection of fuel delivery to muscle as T relates....... This whole thread is becomming rediculous short of some new information.....

SHBG is the main carrier protein for Testosterone, low levels of which will mean that you will have low total testosterone. It also binds estrogen to a lesser extent, however low SHBG levels will also mean you will have higher circulating levels of Estrogen.

The culprit has already been pointed out "insulin"

Get a 12 hour fasting insulin test, Average result for a normal health person should be around 6 to 10 mIU/ml anything above 10 suggests insulin resistance. Most labs will have a range between 2 - 20 mIU/ml for Normal, however they are only looking for abnormalities in the Pancreas such as Insulinomas (Insulin producing Tumours) not for insulin resistance.

There are only a few drugs that will incease SHBG, Diazoxide and Pioglitazone are two of them.

Diazoxide which is used to treat insulinomas lowers the pancreas output of insulin thus increasing SHBG production.

Pioglitazone used to treat Type 2 diabetes reduces insulin resistance and speeds up the removal of insulin thus increasing SHBG.

 

[AlexanderDenmark]

SHBG is the main carrier protein for Testosterone, low levels of which will mean that you will have low total testosterone. It also binds estrogen to a lesser extent, however low SHBG levels will also mean you will have higher circulating levels of Estrogen.

The culprit has already been pointed out "insulin"

Get a 12 hour fasting insulin test, Average result for a normal health person should be around 6 to 10 mIU/ml anything above 10 suggests insulin resistance. Most labs will have a range between 2 - 20 mIU/ml for Normal, however they are only looking for abnormalities in the Pancreas such as Insulinomas (Insulin producing Tumours) not for insulin resistance.

There are only a few drugs that will incease SHBG, Diazoxide and Pioglitazone are two of them.

Diazoxide which is used to treat insulinomas lowers the pancreas output of insulin thus increasing SHBG production.

Pioglitazone used to treat Type 2 diabetes reduces insulin resistance and speeds up the removal of insulin thus increasing SHBG.

I would like to know how you came to the conclusion that SHBG means Low T . Generally people here have it the other way around, low SHBG meaning higher free T.

 

[James23]

I would like to know how you came to the conclusion that SHBG means Low T . Generally people here have it the other way around, low SHBG meaning higher free T.

If SHBG is too low, then the ratio of free T : total T will be too high. Therefore, to keep a normal amount of free T in the body, the body must lower it's production of total T.

The body essentially selects the "lesser of two evils" and lowers T output altogether when it has to decide between:
- excess free T (and therefore excess E2, DHT, etc.), but normal total T
- or, normal free T (and therefore NO excess metabolites) and low total T

 

[BBC3]

Or does the body lower SHBG to counter a TT level that is too low?? Potato/pototo. But which is it, and how to prove??

If SHBG is too low, then the ratio of free T : total T will be too high. Therefore, to keep a normal amount of free T in the body, the body must lower it's production of total T.

The body essentially selects the "lesser of two evils" and lowers T output altogether when it has to decide between:
- excess free T (and therefore excess E2, DHT, etc.), but normal total T
- or, normal free T (and therefore NO excess metabolites) and low total T

 

[James23]

Or does the body lower SHBG to counter a TT level that is too low?? Potato/pototo. But which is it, and how to prove??

One ought to raise T artificially via injections or gel. The body's response will determine which problem is the origin of the situation. If TT output is the problem, SHBG should rise accordingly when we fix that problem. If, instead, SHBG lowers itself when extra T is introduced or an imbalance of FT occurs, then we know that the body is struggling to produce SHBG.

 

[Wheat Thins]

One ought to raise T artificially via injections or gel. The body's response will determine which problem is the origin of the situation. If TT output is the problem, SHBG should rise accordingly when we fix that problem. If, instead, SHBG lowers itself when extra T is introduced or an imbalance of FT occurs, then we know that the body is struggling to produce SHBG.

From what Ive read from Marianco, I think SHBG is more of a symptom and a responses to problems than a cause. I think the next step for people with low shbg who dont respond to TRT is to try TRT with Thyroid support (Ive heard nature throid is better than armour or synthetic but this is unconfirmed by mariano), and maybe adrenal support though I have no idea where to start if the problems are in the adrenals.

 

[markuspartacus]

It is well known that in the early stages of Type 2 diabetes, insulin levels are generally well above average, and the correlation between high insulin and low SHBG is well established.

In fact, screening for low SHBG levels has being suggest as a method of early detection of potential Type 2 Diabetes.
There have also been correlations found between Testosterone and insulin in men, i.e. men with high insulin levels generally have low Total testosterone and visa versa.

So research has shown that Men with High insulin levels have low SHBG and low total testosterone and men with Low insulin levels have high SHBG and high total testosterone levels.

If some men on this forum are on Testosterone replacement therapy and have low SHBG levels then it is very possible that the majority of the increase in their Testosterone levels is due to an increase in free testosterone.

 

[markuspartacus]

Below is a very interesting bit of research which potentially explains and possibly answers the original question.

Associations of Sex-Hormone-Binding Globulin (SHBG) with Non-SHBG-Bound Levels of Testosterone and Estradiol in Independently Living Men -- de Ronde et al. 90 (1): 157 -- Journal of Clinical Endocrinology & Metabolism

The above research shows that High SHBG results in a lower Free Estrogen to Free Testosterone ratio.

 

[maracatu]

I am dealing with this kind of issue.
No success even spliting my testosterone shots bi weekly, arimidex, T4/T3.
My SHBG still very low (10 in a range 13-70) and no response to TRT.

We, men with low SHBG, do not have a solution ?

This is absolutely desperating.

 

[Kwirion]

I am dealing with this kind of issue.
No success even spliting my testosterone shots bi weekly, arimidex, T4/T3.
My SHBG still very low (10 in a range 13-70) and no response to TRT.

We, men with low SHBG, do not have a solution ?

This is absolutely desperating.

Some info: Low SHBG

My SHBG level was low normal: 13 in a range 13-70. TRT with HCG / AndroGel didn't help much..

I tried Clomid- with success - my testoserone level changed from 3 to 12 (range 2 - 12).

My whole story: https://thinksteroids.com/community/threads/134295091

Another case: Nebido testosterone preparation restores fat man?s health

 

[maracatu]

Clomid isn't permanent TRT.
And if you see the Nebido website the SHBG before treatment was 33,9 which is very good.

I would like to know if someone with a low SHBG ( < 15 ) before TRT find a protocol good to restore libido and enegy.

Thanks in advance.
Hope.

 

[Kwirion]

Clomid isn't permanent TRT.

Because..?

I would like to know if someone with a low SHBG ( < 15 ) before TRT find a protocol good to restore libido and enegy.

Copy & paste from another forum / thread

I did 25mg Clomid QD for 2 months (60 days). My labwork is as follows.

12/18/2008:
Total Testosterone: 162 (250-1100)
Free Testosterone: 30.2 (46.0 - 224.0)
Bioavailable Testosterone: 63.5 (110.0 - 575.0)
SHBG: 18 (7 - 49)

01/20 - 01/27: 50mg Clomid QD (7 days)
(switch doctors, get reassigned Clomid)
03/02 - 04/30: 25mg Clomid QD (60 days)

04/06:
Total Testosterone: 1025 (250 - 1100)
Free Testosterone: 189.4 (46.0 - 224.0)
Bioavailable Testosterone: 430.6 (110.0 - 575.0)
SHBG: 26 (7 - 49)
FSH: 13.7 (1.6 - 8.0)
LH: 11.6 (1.5 - 9.3)

Testicular responsiveness to hCG before and after long-term antiestrogen treatment in oligozoospermic men.
Martikainen H, Rönnberg L, Ruokonen A, Vihko R.
Abstract
In order to further investigate the role of endogenous estradiol in the regulation of testicular steroidogenesis an hCG-stimulation test (a single dose of 5000 i.u. i.m.) was performed in 5 normogonadotropic oligozoospermic men before and after 3 months of antiestrogen (clomiphene citrate = CC) treatment (50 mg p.o. daily). Peripheral blood samples were collected immediately before hCG administration and thereafter at 1, 4 and 7 days, and were analyzed for testosterone (T), estradiol (E2), 17-hydroxyprogesterone (17-OHP4), 17-hydroxypregnenolone (17-OHP5), 11 other free and sulfate-conjugated steroids, and for sex hormone-binding globulin (SHBG). The results demonstrated that CC-treatment caused a significant rise in peripheral serum concentrations of SHBG, T, 5 alpha-dihydrotestosterone (DHT), E2 and the sulfate conjugates of pregnenolone, 17-OHP5, 5-androstene-3 beta, 17 beta-diol and T. In the basal state, before the CC-treatment, apparently normal responses to hCG were seen in unconjugated steroids: 17-OHP4 and E2 concentrations were significantly elevated at 1 day, and those of T at 4 days. After CC, only the concentrations of 17-OHP4 rose significantly following hCG administration. The peripheral serum concentrations of the 5-ene- and sulfate-conjugated precursors of T were not influenced by hCG in the basal state or after CC. These results suggest that the apparently E2-mediated inhibition of 17,20-lyase activity in the 4-ene-pathway of T synthesis could not be totally prevented by long-term antiestrogen treatment, and that in the 5-ene-pathway no sign of 17,20-lyase inhibition was demonstrated either before or following CC-treatment. The significant rise in the circulating concentrations of sulfate-conjugated steroids following long-term CC administration, apparently due to increased synthesis of T and its precursors in the 5-ene-pathway, strengthens the concept of their importance in testicular steroidogenesis.
PMID: 4079381 [PubMed - indexed for MEDLINE]

 

[James23]

Kwirion,

I think we have different understandings what "men with low SHBG" describes.

You started out with "SHBG: 18 (7 - 49)", which is not necessarily low given your total testosterone. When you went on Clomid, your SHBG elevated to the ideal level within the range: "SHBG: 26 (7 - 49)" (center of range!)

The problem that people like maracatu and myself share is that SHBG is often lower than 13 to start, and when TRT begins, SHBG goes even lower, often in to the single digits. In your case, you were able to actually raise your SHBG, so I'd be hesitant to lump your case in with ours.

You post an interesting study. However, the study is not one that shows Clomid raising SHBG in men with low SHBG. Rather, it is a study of "healthy" males with fertility problems. The study shows increases in a number of hormones, and the coincident increase in SHBG is likely a symptom of the rise in E2.

I've used Clomid at 15mg/EOD and 30mg EOD. Both of these regimens left SHBG lower than the baseline value at which it started. Needless to say, I felt like shit.

According to some studies, our blunted SHBG expression is entirely genetic and irreversible. This may indicate a permanent inability to balance a healthy level of androgens.

 

[Kwirion]

Hi, OK, now my understanding is better, but...

From research: http://www.mens-hormonal-health.com/normal-testosterone-levels-in-men.html
Optimal SHBG is between 28 - 40, than 18 or below can be seen as low, 7 is just very low.

My SHBG is usually between 12 and 14, (for my age should be 35 - 40) so i know what it's mean.

Literature says that for low levels of SHBG following things must be checked:
- high prolactin
- low thyroid
- insulin resistance
- liver health problems

If all above are OK, there is still possibility to do something.

Current hypothesis for SHBG is that this is a reservoir or buffer (a "waiting room") for testosterone (and other hormones too) for later use as free t.
If SHBG is too low - free testosterone quickly becomes too high and blocks / stops HPTA (due conversion to e2 and DHT etc).

So maybe we need to fool HPTA or block the speedy conversion of testosterone to estrogens and DHT.

Clomid / Nolvadex are SERMs, can block some estrogen receptors etc. So this way should work and help unblock HPTA.

Maybe another way is to block 5alpha reductase and aromatase enzyme.

Therefore I'm proponent of SERMs.

If SHBG is very low (i.e. below 10) than HPTA can by strongly blocked due high androgens conversion. Blocked HPTA means testicles shrinkage.
In such case small doses of Clomid would not help. A full restore protocol like Dr. Scally PCT method is needed.
First HCG for bringing testicle alive back, than full dose of Clomid (50 mg) mixed with Nolvadex 10mg ed.

And by strongly blocked HTPA the first days of PCT restart are painful - man can feel shitty, but must wait a few weeks to restore normal production and testicles functionality.

All above is a little oversimplified but this is a internet forum not university - only the conclusions are presented ;-)

 

[James23]

In such case small doses of Clomid would not help. A full restore protocol like Dr. Scally PCT method is needed.
First HCG for bringing testicle alive back, than full dose of Clomid (50 mg) mixed with Nolvadex 10mg ed.

And by strongly blocked HTPA the first days of PCT restart are painful - man can feel shitty, but must wait a few weeks to restore normal production and testicles functionality.

Is such a high dose (50mg) of Clomid necessary? My TT levels were in the 700's at 25mg/day of Clomid after a single week. Given this fact, would there be a reason to double the dose to reach 50mg and to also add Nolvadex on top of that? I'm just guessing, but it sounds like I'd send myself into the TT:1400's that way. Yikes!

Unfortunately, Dr. Scally claimed, in another thread, that he does not understand how raising T can be bad when SHBG is low. So, I don't have much faith.

 

[zkt]

Dr. M, as usuall, makes the most sense.
Perhaps low SHBG isnt the real culprit but an incidential effect of more far reaching problems.
I fail to see how lowering SHBG would cause such a problem.
Seems to me lowering it would increase the effect of the HPTA feedback, resulting in lower endogenous T and maintaining homeostasis. Thats what the globulins do: regulate the hormonal output via ligand levels resulting in up and down regulating receptor expression,as well as maintaining reserves.