TRT in men with low SHBG

[chris_az]

Dear Doctor J and interested parties,

In the UK I have noticed a strong correlation between fellow
patient's poor response to testosterone and low SHBG.

The widely held belief is that high not low SHBG is a problem.

>From my understanding this is because SHBG is of course the binding
protein (binding 98% of testosterone in the typical male), binding
with greater affinity to testosterone than to E2, therefore high
SHBG adversely affects the testosterone to E2 ratio.

Of course high SHBG can be a problem, but I believe it is more than
a coincidence that many, many men who respond poorly to TRT have low
SHBG, I believe that this too is a problem.

>From what I can see the logic goes that low SHBG will result in a
higher level of free testosterone as less is bound and that this can
only be a good thing. However I think that the problem here is that
SHBG is only being viewed in relation to testosterone.

Low SHBG will also cause an increase in free E2.

Now if this is viewed in the context of testosterone it can be said
that the rise in free testosterone is greater than the rise in free
E2 meaning low SHBG is not a problem because of the binding
affinities.

But like I said this is if SHBG and E2 are viewed in the context of
testosterone. But high E2 in itself is surely likely to cause its
own problems.

I believe those with low SHBG are suffering from high E2, more
specifically high free E2 on TRT and that that is the reason for
poor response to TRT.

My thoughts are merely that, I have no prove whatsoever just a hunch.

Symptomatically those with low SHBG on TRT tend to develop
gynecomastia and see no improvement, in fact sometimes a decrease in
libido on commencement of TRT.

Serum E2 is usually toward the top of the range with no test
available for free E2.

Use of A.Is and anti estrogens seem to have had little benefit to
such men, having had very mixed results.

I am one of these men.

My SHBG is 10nmol/l with a range of 13-75nmol/l.

P.S

There maybe another mechanism of action and my theory maybe wrong, it could be that those with low SHBG share an underlying condition that relates to poor response to TRT, but again this is speculating.

Whatever the mechanism, men with low SHBG who are supposedly those that will do best on TRT are paradoxically those who seem to be fairing the worst.

I would very much like to get to the bottom of why this is. I feel by doing so and finding an answer/reason for this may perhaps pave the way to good health via a TRT protocol which would more appropriate for me and men like me.

A penny for your thoughts?


Regards,

Chris

[HeadDoc]

I wonder whether there is any data around to suggest the relative prevalance of primary vs. secondary hypogonadism? At least that is the way I am interpreting your observations. Did you and your doc do any tests in the beginning to differentiate which type is involved? Since your shbg was low, was your lh also low? I know hcg is a little hard to come by in the UK, have you tried it?

You are also raising a point about who would require ancillary meds for estrogen and aromitization. Interesting thoughts. From many posts here, we know that some do and some do not require ancillaries. That is more observational than explanatory. Sounds like a good topic for a thesis.

[chris_az]

My situation was that the diagnosis was somewhat uncertain despite an MRI and dynamic assessment of the HPTA axis, but I have a long and complicated medical history.

In terms of my thoughts here though, I am not basing them on me because of A) the complications involved in my medical history and B) the fact that this would be an association of one and in that sense insignificant.

The correlation of low SHBG and poor TRT response that I have generally observed is in people in UK via a UK hypogondism forum, people that have not had such complicating factors.

In terms of raising the issue of primary or secondary;

That may or may not be a factor here.

If low SHBG has a statistically significant association with one form of deficiency but not the other, that would be interesting as it may point to the nature of the condition itself and even be used as a diagnostic tool for the assessment of hypogonadism.

However we or at least I do not have information on any study to examine such correlations.

Irrespective of whether primary or secondary forms are linked to low SHBG or not we still have to understand why people on TRT with low SHBG seem to fair badly and what can be done about it?

This is assuming of course for one moment that the association that I have noted isn't just merely coincidental


I am more concerned about the broader facts/details rather than just myself, as I think it is easy to look into my therapy and draw incorrect conclusions from it given other men have not been on the treatments I have.

I will detail my own situation in a different post so as to not cloud the issue as it appears to not just me but a wider number of men

[ASaxon]

That’s scary, I have a low SHBG of 10 (RR: 13 – 71). I guess I really have to watch E2 if this is the case. I’m already concerned with it an am looking into which type of T replacement is best for controlling E2 so I guess I’m going in the right direction at least.

From the way I’m envisioning this, if SHBG is low then TT and FT will be higher on a lower dose of T than someone with higher SHBG. Higher FT, especially in someone who is overweight, will cause a larger conversion of FT to E2 thus raising E2. Seems to make sense but only if FT gets elevated higher than normal. Seems like the amount of E2 would be proportional to the level of FT and the degree by which the patient is overweight.

I would imagine that a lower SHBG would lead to having to take a more careful approach in the balance of dosing T in relation to monitoring E2 and taking an aromatase inhibitor if necessary. I have read that loosing weight can not only raise SHBG (thus being overweight resutls in lower SHBG) but also has the obvious effect of lowering E2 because of the reduction in aromatase conversion. That's the direction I'm hoping to go.

[maxzax]

Originally Posted by HeadDoc

You are also raising a point about who would require ancillary meds for estrogen and aromitization.

Hi Headdoc,

What are ancillary meds?

Sorry for my ignorance.

Thanks!

[chris_az]

I must emphasize, this topic is ONLY based on my subjective observations and the association/correlations that I have noted from the men/pathology/symptoms that I have seen.

From what I have noticed, every single person with very low SHBG has struggled on TRT when according to the view held by the status quo they should be the ones benefiting from it most.

All the men that I have seen with very low SHBG have gynecomastia, all have libido issues, and all have struggled to some extent on TRT, despite adequate replacement and in fact varying doses of TRT.

My theory if it is worth anything is;

Forget the effect of very low SHBG on free T, serum T and in fact androgens period at least for a moment just to get a grip on the concept and think of estradiol, not necessarily the basic pathology number but the possible free E2 level and its most obvious physical symptom- gynecomastia.

Think about the concept of Free E2 and how it could cause problems independent of testosterone.....then go back to thinking about the whole picture.

My thoughts are that everyone, you included only considers SHBG and its effects in relation to free T.

I think this might be incorrect.

Gynecomastia smacks of an E2 problem, so too does very low libido despite adequate T replacement.

If my thoughts have any worth at all and I readily accept that they may not and I could be wrong and the associations I have concluded merely a statistical blip/findings of chance….then it is;

Low SHBG by some mechanism causes gynecomastia, lowered libido and general poor response to TRT.

Hopefully Scott you will fair far better than the men I have come across and myself.

[SPE]

My SHBG was fairly low(don't remember the exact number but my Free T % was 2.64 on a scale of 1.0-2.7), and I've had nothing but success with TRT so far.

[Stez]

My SHBG was very low, either at very bottom of range or even under - I can't remember.

My E2 went to the high end of the range on comencement of TRT. I use 1 dim tablet EOD and it seems to keep my wang working though.

I've had the same theory though. If I have low SHBG, Lowish natural test, and High estro, could taking JUST an anti-e such as DIM lower my estro, and also raise my natural test level through negative feedback?

I think I may have to be the guniea pig on this one...

[chris_az]

SPE,

How low is fairly low?

Can you tell me SPE and Stez respectively;


What were your pathology results for T, E2 and SHBG prior to any meds?
What are your TRT/protocols including all meds?
What are your levels now for T, E2 and SHBG?

That way I can know if we are comparing apples to apples or apples to pears.

[HeadDoc]

Originally Posted by maxzax

Hi Headdoc,

What are ancillary meds?

Sorry for my ignorance.

Thanks!

AI's, I3C/DIM, etc. Meds/supplements for estrogen conttrol.