T Nation

Question For Bill Roberts


#1

I've really enjoyed reading Bill Roberts' thorough and informative responses to other posts on these forums and have a few questions that I would like to ask him. I would send a PM if the option were available, but since it is not, I am posting publicly. Hopefully other members of this forum will find the information useful if he chooses to respond.

To be as succinct as possible: what is the most useful criteria for determining whether or not someone would benefit from TRT? Obviously if Total T is low and someone is symptomatic, the answer is fairly clear. However, what about cases in which, for instance, abnormally high SHBG is combined with low Free T and "artificially" inflated total T numbers? If someone with symptoms of Low T presents with high/normal total T but low free T, would treatment be recommended or would it be best to search for other causes of the symptoms? Endocrinologists seem to disagree about this point, or simply aren't knowledgable enough to have an opinion.

For full information on my case and relevant labs, please see this link: http://tnation.T-Nation.com/hub/TrevorLPT#myForums/thread/6119642/

Included in the last post in that thread are other questions I have about my case and current course of treatment (Dr. prescribed T3/T4) that likely are not relevant to anyone else so I won't copy here. However, any insights into my case would be greatly appreciated.

Thank you in advance for any help or information that you may offer.


#2

Reviewing your thread, sound opinions and advice were given consistently by KSman and your doctor. I certainly see your point in wanting to consider testosterone replacement therapy while also seeing your doctor’s reasoning in not doing so.

A disadvantage of starting hormone replacement therapy is that it strongly tends to become an irreversible decision, making a person dependent for the rest of his life.

If it were me I would like to see what happens when estradiol is reduced to low 20’s pg/mL before starting hormone replacement therapy.

I’m not confident that this will make for much improvement, as your LH and FSH are quite good already, but there’s a chance.

If that did not work, I would insist on self-administration of the prescribed testosterone and use the minimum necessary to get free T to midrange, while keeping estradiol in the low 20’s. This might succeed in preserving normal LH and FSH production, making it a reversible decision if desired.

I have a couple of other thoughts on your symptoms.

One is that you might be suffering from unsynchronized circadian rhythms. What this means is that there’s a circadian rhythm not only for your wakefulness, which tends to be set by light/dark pattern, but every organ in the body has its own circadian clock. Very, very preferably they’re in sync with each other. In some instances, such as shift work, diabetes, or obesity, the organs are typically out of sync. This has adverse metabolic consequences; also as not-fully-based opinion, it can result in strange body temperature patterns even when thyroid is good. (It is a fact that body temperature patterns can be strange and low while thyroid is good; it’s opinion that circadian rhythm of the organs is related to this.)

Actions to take on the chance that this is related would include the obvious of honoring the natural light/dark cycle and having consistent sleep times, and also avoiding eating late at night and especially in the middle of the night.

Another is that there is some similarity in your experiences with chronic fatigue syndrome, which I don’t say that you have, or even that it is necessarily one specific thing rather than a constellation of symptoms which has measurable markers associated with it and some response patterns. An important issue with CFS, which may be related to your situation, is the gut microbiota, which can be varied according to diet. There have been studies with fecal transplantation which I expect you have no interest in, but the point being, changing the gut bacteria can change outcome. I would not put too much stock into commercially available products let alone yogurts, though one of the refrigerated health store products might help slightly. Rather I’d look towards increasing microbial diversity from intake of various foods which have bacteria which may survive to the gut and which are associated with the natural human condition, such as found on vegetables, including those growing down in the dirt, which haven’t been washed too much; and with home-fermented or home-style-fermented (commercial may be quite dfifferent) foods. There are also diets which tend to imbalance the gut microbiota, and ones which are restorative. Paleo type diets are restorative. High cyandin-3-glucoside intake also favorably affects gut microbiota balance.

The CFS-like hypothesis, while not necessarily right, would also tie in with your thyroid experiences.

At any rate those steps could not hurt and might help.


#3

Bill, thank you for you quick and helpful reply.

I agree that I have gotten good advice from KSman and my doctor and am thankful for their help. On the point of TRT being a permanent decision, why is it that many people are able to do cycles of AAS lasting 16+ weeks with testosterone doses much higher than those used for TRT and seemingly recover completely after cycling off, but that is rairly discussed as an option for TRT users? I am asking particularly about cases where a patient may want to “try” TRT for a few months to see what kind of impact it has on their symptoms.

Are there non-pharmacutical methods for reducing E2 to that range or would you recommend low-dose arimidex?

Your comments about testosterone self-administration have been noted and are greatly appreciated.

That is interesting about circadian rhythms. I have a normal sleep/wake schedule (in bed by 11:30, awaken naturally by 8:30) most days. However, I have noticed that periods of my life where I feel particularly fatigued are accompanied by odd sleeping and waking habits, such as inability to fall asleep at the normal time, waking often throughout the night, and/ or sleeping in much later than usual.

I will research more about gut microflora, although that has been an area of interest to me for a while. I currently take a refrigerated probiotic pill and ingest a few fork-fulls of kimchi (fermented cabbage) almost daily.


#4

I don’t have a numeric figure but rather than it being the norm for AAS users who do 16 week cycles to reliably recover natural testosterone production, it’s very common for them to not do so and soon – not necessarily first cycle, but soon – become “blast and cruisers” or resort to HRT. The problem could have been virtually eliminated by keeping cycle length to 8 weeks but for many this is a difficult thing to persuade them on.

As for trying a TRT dose for 8 weeks and then doing a standard steroid cycle PCT, that’s always an option. It’s a great point and indeed should be talked about a lot more.

A further aspect is that if natural T production is low already, then adding another insult (so to speak) could make potential recovery even more challenging. Among AAS users, those with more marginal production in the first place strongly tend to have more prolonged recoveries as well, which might apply to non-AAS users as well. I’d encourage first doing everything within reason to try restoring natural production and then if desired try HRT on a trial basis, with a planned discontinuance date within a time such as 8 weeks unless becoming “sold” on it and choosing to make HRT a perhaps-irrevocable or at least very hard to reverse decision.

Pharmaceutical methods such as Arimidex are the way to specifically control estradiol, other than bodyfat changes which shouldn’t be neglected if that’s a culprit, but which is a much slower remedy of course.

I’m not an expert on the matter but I’ve seen claims commercial fermented vegetable foods are usually pasteurized, which would completely (or nearly so) defeat any probiotic purpose. Another aspect would be genetic diversity of the microbiome, which research is indicating to be quite important. Commercial products will use relatively few strains.

It’s quite easy to ferment vegetables oneself, preferably, as opinion, using farm fresh produce from an organic-type-but-not-necessarily-certified local source, with only light washing beforehand.

Historically, it’s extremely abnormal to be consuming only or almost only foods which are sterilized either beforehand of the bacteria we’d normally be exposed to, or steriized by ourselves in boiling water.

The probiotic pills are probably better than nothing but probably as opinion greatly inferior to allowing natural bacteria from food plants that aren’t sterilized.


#5

Bill,

Thanks so much for all of this information.

I would appreciate any input you have on my current course of thinking about my case. I have been advised that short term use of low-dose oral stanozolol may lower my SHBG, and the studies I’ve seen appear to bare this out. But what I’m wondering is this: does lowering SHBG actually raise Free T, assuming Total T levels are sufficient? With as much attention that lowering SHBG seems to get, you would think that more people would be looking at this and we would have a definitive answer, but I have not been able to find one. Essentially, I’m interested in lowering my SHBG, but there would be no reason for me to go down that road unless it resulted in more Free T. Do you have any input on this?

Additionally, I have been considering your suggestion of lowering E2 through the use of an AI, but my worry is that this would end up being a life-long pharmaceutical solution. If I’m going to be taking medication to regulate hormone for the rest of my life, I don’t see a significant benefit to using only an AI over a more comprehensive TRT protocol. I would like to exhaust any options that are A. short-term but present long term improvements (lowering SHBG with stanozolol, potentially) or B. non-pharmacutical.


#6

Lowering SHBG does not provide an advantage.

I know that many advise that it does, on a theory that it’s going to release considerable testosterone that is bound. (Never from practical observation of how much benefit was experienced!)

The theory is completely wrong on more than one level.

How much testosterone is bound to SHBG? Well to have convenient numbers, let’s say that total T is a little over 1000 ng/dL, of which exactly 1000 ng/dL happens to be bound to SHBG.

How much testosterone is that, if you have 5 liters of blood? 50 deciliters times 1000 nanograms per deciliter comes to 50 micrograms of testosterone. If you could make it all release, it would be like getting an extra 50 [micrograms of testosterone, as a one-shot deal.

Big deal!

The other and more important level is that receptor binding has to do with the chemical potential of the testosterone in solution, and this is not affected at all by agents acting at SHBG (other than from the utterly trivial concentration increase achieved on a one-time basis, gone within minutes, from the 50 milligram release if it occurred.)

More importantly, in practice it does not increase results to drive down SHBG.


#7

Very interesting! And that certainly does fly in the face of “conventional wisdom” about shbg.

Since this is the case, why is it that free testosterone is usually considered superior to total testosterone when determining overall hormone status? If freeing up testosterone from shbg provides no benefit, then why even differentiate between free test, total test, and bio available test? Wouldn’t the guy in your example have 0 free test and exhibit signs of severe hypogonadism? Importantly to my case in particular, how can you raise free test if lowering shbg won’t do the job?


#8

Of the three things you mention – free testosterone, “bioavailable testosterone” (pretty much free T plus that bound to serum albumin) and total testosterone (pretty much free T plus that bound to serum albumin plus that bound to SHBG) only free T is directly proportional to chemical potential and directly relevant to to receptor binding.

Amount bound to serum albumin is completely a result of the amount of serum albumin and the amount of free T. It adds no information other than the amount of serum albumin. Which has nothing to do with androgenic activity.

Amount bound to SHBG is completely a result of free T and the amount of SHBG. It adds no information beyond those of a free T measurement and a SHBG measurement.

That fact, however, enables a practical, useful calculation of free T from total T and SHBG. It’s a completely acceptable method of measuring free T and judging activity of testosterone.


#9

Rasing free T is more a question of addressing problems than achieving positive action, unless using HCG to do the job.

Specifically if estradiol is high, prolactin is high, or thyroid function is poor (if so by all means do NOT follow the advice to megadose iodine: 1 mg/day is sufficient and 2 mg/day is a reasonable max for a couple of weeks) then correcting these things can often improve free T. Other issues such as stress, excessive bodyfat, or disrupted circadian rhythm can also be problems which if corrected would result in improved free T. Still another is poor free T due to a diet with excessively low fat (under 30%, with about 40% being optimal) or too low in saturated fat.


#10

[quote]Bill Roberts wrote:
Of the three things you mention – free testosterone, “bioavailable testosterone” (pretty much free T plus that bound to serum albumin) and total testosterone (pretty much free T plus that bound to serum albumin plus that bound to SHBG) only free T is directly proportional to chemical potential and directly relevant to to receptor binding.

Amount bound to serum albumin is completely a result of the amount of serum albumin and the amount of free T. It adds no information other than the amount of serum albumin. Which has nothing to do with androgenic activity.

Amount bound to SHBG is completely a result of free T and the amount of SHBG. It adds no information beyond those of a free T measurement and a SHBG measurement.

That fact, however, enables a practical, useful calculation of free T from total T and SHBG. It’s a completely acceptable method of measuring free T and judging activity of testosterone.[/quote]

Excuse me if I’m being dense, but if all this is true, doesn’t it follow that reducing SHBG is beneficial in raising Free T, which is the only number that we should really care about in this equation?

What I mean is this: if high/ normal Total T + normal albumin + high SHBG = low Free T, and high/ normal Total T + normal albumin + normal SHBG = high/ normal Free T, then wouldn’t it be beneficial to bring SHBG back to normal range if it is currently and chronically high? Why would reducing SHBG not have an effect on Free T levels if adequate Total T is present and SHBG is high?

And to be clear, I am speaking purely about someone who is not taking exogenous testosterone and has naturally “good” levels, with the exclusion of SHBG (high) and Free T (low).


#11

I think I could answer your question better if you let me know why or how you are thinking reducing SHBG would affect free T? In an example similar to yours, but let’s make it more specific where SHBG is in the normal range but high, free T is low, and total T is normal but of course will not be high normal given the above.

And what would the means be of reducing SHBG? For example, a supplement product that is supposed to displace testosterone from SHBG? Let’s not make it by reducing estradiol, as that would have its own effects.

If I answer without that I might be answering a reason entirely different than you’re thinking, and thus not any help (I’m guessing that that would happen, because my above reply proved not to answer your reason.)


#12

I would really be interested in any available answer to this as well. I have reasonably high total T, sky-high SHBG, and very low free T. LH and FSH are also high. I also have low thyroid hormones, but am on long-term T3 and T4 as well as moderate supplementation with kelp. What’s interesting is I don’t seem to have the terrible problems that so many on here have come with. Performance in the gym and bedroom have been pretty good without much decline over the years (could always be better of course). I’m 54.

I have searched and searched and there doesn’t seem to be any answer to the high SHBG problem other than “TRT”. Doctor says the same thing. I ran across the possibility of testicular cancer, but Doc says that’s a young man’s disease. I’m just very reluctant to go on a one-way TRT/HRT trip without the symptoms being much worse. Any ideas?


#13

T3 can raise SHBG, which could explain your result there.

LH being high yet free testosterone being low suggests that the problem is with reduced testicular production. Unfortunately I don’t know an answer to that when LH has been high already.


#14

[quote]Bill Roberts wrote:
I think I could answer your question better if you let me know why or how you are thinking reducing SHBG would affect free T? In an example similar to yours, but let’s make it more specific where SHBG is in the normal range but high, free T is low, and total T is normal but of course will not be high normal given the above.

And what would the means be of reducing SHBG? For example, a supplement product that is supposed to displace testosterone from SHBG? Let’s not make it by reducing estradiol, as that would have its own effects.

If I answer without that I might be answering a reason entirely different than you’re thinking, and thus not any help (I’m guessing that that would happen, because my above reply proved not to answer your reason.)[/quote]

My thinking is that if normal Total T + High SHBG = low Free T and normal Total T + normal SHBG = normal Free T, then taking SHBG from high to normal would take free T from low to normal. Put another way, if Free T is a measure of Total T + SHBG, wouldn’t adjusting SHBG effect Free T, assuming that Total remains constant?

The means of reducing SHBG would be very low dose stanazolol for 4-6 weeks. I have been told by a seemingly knowledgable Dr. that this could potentially lower SHBG for up to 6 months.


#15

How would it take free T from low to normal?

By releasing all the T that is bound to SHBG?

That is only about 50 micograms (1/20th of one milligram) of testosterone, and releasing it would be a one-shot deal.

So that way would not work, and I don’t know another mechanism. SHBG does not work against testosterone in any way: it helps transport it. I’d be glad to address another suggested way in which reducing SHBG might increase free T.


#16

[quote]Bill Roberts wrote:
How would it take free T from low to normal?

By releasing all the T that is bound to SHBG?

That is only about 50 micograms (1/20th of one milligram) of testosterone, and releasing it would be a one-shot deal.

So that way would not work, and I don’t know another mechanism. SHBG does not work against testosterone in any way: it helps transport it. I’d be glad to address another suggested way in which reducing SHBG might increase free T.[/quote]

I am not clear on the mechanism, but I suppose “by releasing all [or some] of the T that is bound to SHBG” describes what I am imagining.

If SHBG is chronically high, and I were to find a way to consistently lower it so that it always tested within the normal range, would it then still be a “one shot deal?”

I guess I’m just getting hung up on this because it seems so simple on paper. To use your own example, if a guy had a total test of 1000 ng/dl and such high SHBG that ALL of his test was bound to it, wouldn’t he have a Free T of 0 and feel awful? And if that guy found a way to consistently, lets say, reduce his SHBG to such a level that half of his total test was now free – wouldn’t that raise free T and alleviate symptoms?

I understand what you are saying about the total amount of serum testosterone in the blood bound to SHBG being insignificant. However, doesn’t the same logic say that increasing free testosterone from 5 pg/ml to 50 pg/ml provide no benefit, because the ACTUAL increase in testosterone would be so astronomically small (0.5 micrograms, assuming 5 liters of blood as you did in an earlier post)?


#17

No, because the receptors don’t respond to knowing how many micrograms, milligrams, or grams of testosterone is in the body as a whole, or in the blood as a while, but to the chemical potential of testosterone at their location, which is a function of the free testosterone concentration only.

Part of why the free testosterone is a very low concentration is what is called partitioning. A substance may “prefer” to be dissolved in one thing rather than another, for example in fat or oil than in water, or bound to a protein rather than free in water, and will exhibit a constant ratio in the amounts dissolved in each or bound versus dissolved. In the case of testosterone, it has scarcely any solubility in water, so at any given moment only a very small fraction of the amount in the body is free in water. That concentration, however, is what does the job.


#18

[quote]Bill Roberts wrote:
T3 can raise SHBG, which could explain your result there.

LH being high yet free testosterone being low suggests that the problem is with reduced testicular production. Unfortunately I don’t know an answer to that when LH has been high already.[/quote]

I ran across the T3 issue also, but I don’t think that’s it. I’m taking a very small amount of T3 (generic Cytomel) in combination with a larger amount of T4 (generic Synthroid), trying to get free T3 up to mid-range and afternoon temperature up. Free T4 is already in upper range.

Anyway, the real question we seem to be dancing around is this- if one has reasonably high total T, high SHBG, and low free T, is the only “solution” additional (and therefore ultimately total replacement) testosterone? Does that “overcome” the high SHBG? Will reducing E2 (if high) contribute anything to the “solution”.

Thanks!


#19

It’s not a question of “overcoming” SHBG. The SHBG is helping transport the testosterone. It is not using it up. As it happens, a given amount of blood will measure more content of testosterone if there’s more SHBG there as well, but so far as the receptors are concerned, the free amount is the only relevant amount. The SHBG is a depot, a reservoir, a bus, a warehouse (a tiny one, but even so.) It is not a consumer, a metabolizer, a destroyer etc.

Unfortunately yes, if the testes don’t produce enough testosterone despite high LH, then usually the only answer is testosterone replacement therapy (HCG won’t work either.) An exception could occur if the reason is iron toxicity, but that’s a relatively rare reason.


#20

(Sorry, I should have made this a new thread, but I can’t cancel the post now.)

(Sorry, I should have posted in new thread! I misread, thought this thread was “QuestionS For Bill Roberts”)

Bill, would you care to weigh in on GW 501516?

It sounds like a miracle drug, but I’m not sure how to estimate the real risk of cancer. Some of the statements made regarding risk seem to have been exaggerations to more effectively discourage use. For example, the New Scientist in 2013 reported that “tests on rats showed that at all doses, the drug rapidly causes cancers in a multitude of organs, including the liver, bladder, stomach, skin, thyroid, tongue, testes, ovaries and womb.”

However, this statement came at a time when WADA was trying to discourage use by athletes seeking to improve endurance. Since I can’t get my hands on the original data, I’m at a loss to sort this out… what do you think??

Thanks much for all of your contributions.