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Blackhawk

Member
Then why according to the late Dr Crisler do low SHBG guys exctrete so much more free testosterone in their urine and apparently have higher spikes/ lower troughs of Free testosterone.
 
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Cataceous

Super Moderator
Then why according to the late Dr Crisler do low SHBG guys exctrete so much more free testosterone in their urine and apparently have higher spikes/ lower troughs of Free testosterone.
Excess excretion is expected if the low-SHBG guy is dosed so that his total serum testosterone matches the high-SHBG guy. In my previous example, if the guy with an SHBG of 10 nmol/L has his testosterone dose doubled so that his serum testosterone matches the 1,000 ng/dL of the high-SHBG guy, then his excretion rate is doubled—as a result of doubled free testosterone.

I'd like to see the evidence for higher peaks and lower troughs in free T. If free T is roughly linear in T then it's claiming a shorter apparent half-life, which isn't possible unless something really unusual is happening with the non-SHBG-related metabolic clearance rate of testosterone.
 

Blackhawk

Member
I understand the dosing frequency issue as related to relative metabolism of free T vs SHBG bound T. These are two different molecules with different tendencies in metabolism, I see nothing contrary to Crisler's explanation as I would not expect the T bound to SHBG molecule to have the same rate of uptake and elimination as Free T.

Bowing out of this discussion from here. I am not that knowledgeable to add anything more except rewording what I already have said.

It's all yours.
 

Cataceous

Super Moderator
I understand the dosing frequency issue as related to relative metabolism of free T vs SHBG bound T. These are two different molecules with different tendencies in metabolism, I see nothing contrary to Crisler's explanation as I would not expect the T bound to SHBG molecule to have the same rate of uptake and elimination as Free T.
...
I'd be very interested in any references on this. My understanding is that SHBG primarily serves as a reservoir, which can restore depleted free testosterone, but at a much slower rate than albumin. More recently it was discovered that SHBG can deliver testosterone directly in some situations, but it's not clear to me how significant this is relative to overall activity. As I see it, there's still no clear explanation of the benefits of frequent injections for low-SHBG guys, though estradiol could well be a contributing factor.
 

DDD

Member
Once T is cleaved from the ester it either becomes free T or is bound to SHBG or Albumin.

Free T is very short acting and is used up rapidly.

Guys with low SHBG have much more essentially released into the system as free T which is used up rapidly and also rapidly excreted in urine if there is excess not bound to SHBG. These guys essentially burn up the supply faster and levels subsequently crash much faster, so smaller more frequent doses are appropriate to help keep levels more stable rather than running out after 2-3 days and crashing before the next dose. In terms of numbers, some of the guys on this forum have very low SHBG in the teens.


T bound to SHBG remains in the body much longer.

More SHBG means you bind up more T and it is retained in the body over a longer time period. As such, guys who have high SHBG tend to need larger cumulative total dose injecting T to achieve good Free T levels since so much is bound by SHBG. They tend to have lower Free T in relation to total T. It is kind of like there is a better long term storage system in place with higher SHBG, and this man does not burn up the available free T as fast. However, some men with higher SHBG like me actually also do better on more frequent dosing as well. For me theoretically it helps reduce estrogen by taking smaller more frequent doses compared to larger less frequent doses. My SHBG is currently ~52 which is high but not radically so. It can reach quite a bit higher in some men.


The bottom line is larger every other week or weekly doses create a "roller coaster" effect where Free T trough level is too low to feel good. The half life of T is about 8 days which means you lose close to half the amount of T you inject in about a week. 50% lower level can cause ill effects. Low SHBG guys burn up the Free T even faster and some need every day dosing to feel OK.


Thanks, man, for that explanation. I understand SHBG now a little better. I just had labs done this week including SHBG and am waiting results. But I think my SHBG is usually in the 20s. I am currently on a once a week regimen injecting 150mg (.75cc) on Mondays and taking .25mg anastrozole on Tuesdays and .1mg anastrozole on Fri and Sun. My T is usually around 1200 the day after injection (Tuesday) and 500 seven days later before the next injection. (sometimes I measured 700). Sometimes I think I feel a little different by Sat and Sun when my T is lower. Should I "feel" a difference between 1200 and 500/600? I am thinking of going back to twice weekly.
 

Blackhawk

Member
Thanks, man, for that explanation. I understand SHBG now a little better. I just had labs done this week including SHBG and am waiting results. But I think my SHBG is usually in the 20s. I am currently on a once a week regimen injecting 150mg (.75cc) on Mondays and taking .25mg anastrozole on Tuesdays and .1mg anastrozole on Fri and Sun. My T is usually around 1200 the day after injection (Tuesday) and 500 seven days later before the next injection. (sometimes I measured 700). Sometimes I think I feel a little different by Sat and Sun when my T is lower. Should I "feel" a difference between 1200 and 500/600? I am thinking of going back to twice weekly.


Not really about how SHOULD you feel, the real question is how DO you feel? If you are feeling good throughout the week, that's great and unless something changes go with it.

It also does not hurt to experiment (Within reason) so if you try splitting your dose, maybe you'l learn something. You could end up feeling better or worse. It is all individual. The catch is, changes take around 4-6 weeks to stabilize, so don't expect the next steady state for a while. Sometimes changes can feel good in that adapting phase. other times things can feel bad, but you don't know the end result until you fully wait it out. It takes me even longer to fully reach equilibrium especially when lowering dose, around 2-3 months to fully adjust.

By the numbers, your peak vs trough is pretty dramatic. If SHBG is in the high 20s, and if you do actually have low SHBG, you may do better on every three or every other day schedule. If it is more like 20, maybe EOD or daily, and very possibly lower cumulative dose for total weekly more like 100 or below. YMMV, just seems this kind of dosage and schedule tends to work better for lower SHBG guys who have posted to this forum.

Total T is an inferior reference as to how your protocol is effecting you.

Track your Free T and E2 sensitive LC/MS/MS. Base any AI dosing on E2 number and symptoms, and pay attention to high vs low E2 symptoms.
 

Systemlord

Member
But I think my SHBG is usually in the 20s. I am currently on a once a week regimen injecting 150mg (.75cc) on Mondays and taking .25mg anastrozole on Tuesdays and .1mg anastrozole on Fri and Sun.


TRT will lower your SHBG a little bit and I don't expect this protocol to be ideal for you since you more than likely find SHBG <20 on your next set of labs.
 

DDD

Member
Not really about how SHOULD you feel, the real question is how DO you feel? If you are feeling good throughout the week, that's great and unless something changes go with it.

It also does not hurt to experiment (Within reason) so if you try splitting your dose, maybe you'l learn something. You could end up feeling better or worse. It is all individual. The catch is, changes take around 4-6 weeks to stabilize, so don't expect the next steady state for a while. Sometimes changes can feel good in that adapting phase. other times things can feel bad, but you don't know the end result until you fully wait it out. It takes me even longer to fully reach equilibrium especially when lowering dose, around 2-3 months to fully adjust.

By the numbers, your peak vs trough is pretty dramatic. If SHBG is in the high 20s, and if you do actually have low SHBG, you may do better on every three or every other day schedule. If it is more like 20, maybe EOD or daily, and very possibly lower cumulative dose for total weekly more like 100 or below. YMMV, just seems this kind of dosage and schedule tends to work better for lower SHBG guys who have posted to this forum.

Total T is an inferior reference as to how your protocol is effecting you.

Track your Free T and E2 sensitive LC/MS/MS. Base any AI dosing on E2 number and symptoms, and pay attention to high vs low E2 symptoms.

My free T numbers usually test on the high side of the range or above the range. With E2, 24 hours (Tuesday) after my weekly injection the E2 can be anywhere from 37-53. By Friday before I take the .1mg anastrozole it has tested at 30. Then Monday before my next injection it has tested around 17.

I did labs last week before and after injection, so I'm waiting for those results.
 

Tman

Active Member
I'd been hoping someone would make a statement like this so we could have a more detailed discussion. The problem is that low-SHBG guys cannot "burn up the supply faster" because the limiting factor is the rate of supply, not the rate of clearance. That is, I've seen no evidence that the rate of testosterone absorption from an injected depot is affected by one's SHBG. Yet this absorption rate is the primary driver of the apparent serum half-life of testosterone, as opposed to the consumption side, in which the effective metabolic clearance rate is directly influenced by SHBG.

Consider this analogy with two tubs of water, one draining into another: the upper tub of water represents an injected depot of a testosterone ester. The lower tub of water represents testosterone in the body. The lower tub has a decent-sized drain opening that represents the testosterone being metabolized and eliminated. The upper tub has a small drain leading to the lower tub. In each tub the rate of flow out of the drain is proportional to the height of water in the particular tub. SHBG represents the size of the lower tub's drain, larger for low SHBG, smaller for high SHBG. The point is that this does not affect the upper tub's slow draining, which is what sets the apparent serum half-life.
yeah but even using your analogy since the upper tub drains more slowly the lower tub will empty before and remain low throughout because the upper tub isn't flowing as fast. however a high is hbg guys drain would be smaller and flow less in the lower tub which means it would actually fill with water and hold on to the testosterone which is what is happening.
 

Tman

Active Member
I'd be very interested in any references on this. My understanding is that SHBG primarily serves as a reservoir, which can restore depleted free testosterone, but at a much slower rate than albumin. More recently it was discovered that SHBG can deliver testosterone directly in some situations, but it's not clear to me how significant this is relative to overall activity. As I see it, there's still no clear explanation of the benefits of frequent injections for low-SHBG guys, though estradiol could well be a contributing factor.
Then you need to keep researching it because the correlation is clearly established lower shbg results in higher free t numbers with the same dosage compared to a person that has high shbg.
 

Cataceous

Super Moderator
yeah but even using your analogy since the upper tub drains more slowly the lower tub will empty before and remain low throughout because the upper tub isn't flowing as fast. however a high is hbg guys drain would be smaller and flow less in the lower tub which means it would actually fill with water and hold on to the testosterone which is what is happening.
You neglect the important difference stated between these imaginary tubs and real tubs: these tubs can never fully empty because the flow rate out is proportional to how much is in them and to the drain sizes. So the lower the level the slower they drain. This is how things work in the body: the clearance rate is proportional to concentration.

The other important assumption is that the lower drain is always much larger than the upper drain. This is also physiological, as the half-life of testosterone in serum is on the order of minutes, whereas the injected depot is supplying testosterone with a half-life of days. Under these conditions the changes in the lower drain size change the lower tub water level proportionally, but they don't change the flow rate out of the lower drain, which must end up matching the flow rate in from the upper drain; if you suddenly halve the lower drain size then the water level rises to double where it was and the outflow again matches the inflow.
 

Cataceous

Super Moderator
Then you need to keep researching it because the correlation is clearly established lower shbg results in higher free t numbers with the same dosage compared to a person that has high shbg.
What 's clearly established is that in two guys with the same total serum testosterone, the one with lower SHBG has greater free testosterone than the other, assuming similar albumin. The correlation you seem to be referring to is going to be pretty weak. Which is to say that if you pick two guys at random and give them the same testosterone dose, then the likelihood that the one with lower SHBG will have higher free T is probably only a few percent over 50-50.
 

Mr S

Active Member
What 's clearly established is that in two guys with the same total serum testosterone, the one with lower SHBG has greater free testosterone than the other, assuming similar albumin. The correlation you seem to be referring to is going to be pretty weak. Which is to say that if you pick two guys at random and give them the same testosterone dose, then the likelihood that the one with lower SHBG will have higher free T is probably only a few percent over 50-50.
Would I be considered to be leaning toward becoming a high SHBG guy per labs range?
 

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Bjjpapi

New Member
Just watched Nelson’s video on YouTube explaining how HCG helps other hormones stay in balance due to HCG mimicking FSH and LH (after FSH and LH drop due to TRT). Made a lot of sense to have a protocol that involves HCG if the info in the video is correct.

 

Mr S

Active Member
Has anything changed concerning HCG and Nelson’s viewpoint on the same? I mean either anecdotally or research wise.
 

DDD

Member
TRT will lower your SHBG a little bit and I don't expect this protocol to be ideal for you since you more than likely find SHBG <20 on your next set of labs.


Here are my most recent labs taken on the once a week injection schedule. Both times SHBG was 13.

First lab was taken at the end of the weekly cycle right before my next injection.
T-- 678 (range 250-1100)
Free T-- 158 (range 35-155)
Estradiol-- 20 (range 29 or below)
SHBG-- 13 (range 11-50)

Second lab taken two days after injection and one day after .25mg anastrozole.
T-- 1217 (range 250-1100)
Free T-- 321 (range 35-155)
Estradiol-- 22
SHBG-- 13 (range 11-150)

I am getting ready to switch to twice weekly.
 

Systemlord

Member
I am getting ready to switch to twice weekly.

Your lab results are not typical of men with low SHBG, Total T is above mid-range and Free T is near the top. You do not see a large decline in levels after 6 days either.

Twice weekly should do nicely.
 

DDD

Member
Your lab results are not typical of men with low SHBG, Total T is above mid-range and Free T is near the top. You do not see a large decline in levels after 6 days either.

Twice weekly should do nicely.


What do you mean my labs are not typical of men with low SHBG? Can you explain a little more? My FT at peak is nearly double the high end of the range, and my FT at rough is still above the upper limit. Is that OK?
 
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