Testosterone propionate supposedly the best ester?

Seagal said:

Would that mean that also FT should be lower?

Click to expand...

Seagal said:

Don't understand then why FE2 would not remain unchanged too.
...

Click to expand...

Seagal said:

...
Could you please link scientific literature that explains the 'pond' model. Sorry, but that has never made sense to me.

Click to expand...

Cataceous said:

No. In theory, at steady state it should not change. This applies to TRT with constant dosing. Otherwise you have to consider possible HPTA suppression.

Here's an analogy: Think of SHBG as a pond with water flowing in and out. Free testosterone is analogous to the water running out. Now consider mesterolone as a bunch of boulders you throw into the pond. When this happens there is a transient surge of out-flow—free testosterone—but over time the flow of water leaving the pond again matches what's flowing in.

Click to expand...

Cataceous said:

In this simple model free estradiol would not change, but it's believed that in reality—free—mesterolone is independently interfering with aromatization. The extent of this interference is uncertain.


As far as I know these simple water flow models, including the sponge model, are creations local to ExcelMale. The idea is to make the processes more familiar and intuitive, versus less familiar concepts such the equilibrium between associations and disassociations at binding sites.

What part of these models do not make sense? The idea is that SHBG is basically a storage medium, and hormones are viewed as flowing from creation/introduction through the storage medium to their eventual metabolism and elimination. There's obviously a lot of simplification going on, but I don't think it overly distorts a basic understanding.

Click to expand...

Cataceous said:

It might be possible to quantify this, though it gets complicated. Here are a couple of the elements—chime in with any others you can think of: the androgenic action of mesterolone leads to reduced production of SHBG and lower levels; mesterolone's strong binding potential for SHBG displaces testosterone and estradiol, effectively further reducing SHBG. This latter can lead to "a reduction in [total] serum E2 (which cannot be explained by and is disproportionately higher than the reduction of SHBG)." The question then is, how can you be sure this is not the phenomenon being observed, as opposed to aromatase inhibition? The observations with DHT fit in this scenario because DHT has a much lower binding affinity for SHBG than does mesterolone.

The key point is that real and effective reductions in SHBG do not affect the free hormone levels at steady state. Thus the way to resolve this issue is to accurately measure free estradiol at baseline and while using mesterolone. A decrease in free estradiol could be reflective of lowered production via aromatase inhibition.

Click to expand...

Seagal said:

...
Let's take the case that seems to be accepted as fact by. Bro Science, validated by measurements of blood FT increases when proviron is added to exogenous T.
...

Click to expand...

Seagal said:

I'm really willing to read up on the details that come with
equilibrium between associations and disassociations at binding sites, if they come along with scientific publications.

Click to expand...

Cataceous said:

It can be acknowledged that aside from suppressing the production of SHBG, mesterolone also ties up some fraction of the reduced level of SHBG, which leads to an even lower effective level. Conventional wisdom had held that this loss of SHBG leads to more free testosterone. However, it's increasingly well established that isolated changes in SHBG affect the free hormone levels only transiently. If you want to get into the weeds on this then research restrictively metabolized drugs. Testosterone is in this category, and the implication is that the clearance rate is proportional to the concentration. From this it follows that the dose rate or production rate proportionally determines free testosterone, independent of SHBG.

@Gman86 presented some nice anecdotal evidence here. He made one change in his protocol, switching to exemestane from anastrozole. This knocked down his SHBG from 51 to 36 nMol/L. But total testosterone also dropped, and free testosterone remained essentially unchanged.

If mesterolone is increasing free testosterone at steady state then it would have to be through altering the metabolic clearance rate constant. So far I've seen no evidence in support of this.


I'm sure there are dozens, if not hundreds of such publications. But with these there is some danger of not seeing the forest for the trees. The simple analogies are meant to avoid that.

Click to expand...

Cataceous said:

It can be acknowledged that aside from suppressing the production of SHBG, mesterolone also ties up some fraction of the reduced level of SHBG, which leads to an even lower effective level. Conventional wisdom had held that this loss of SHBG leads to more free testosterone. However, it's increasingly well established that isolated changes in SHBG affect the free hormone levels only transiently. If you want to get into the weeds on this then research restrictively metabolized drugs. Testosterone is in this category, and the implication is that the clearance rate is proportional to the concentration. From this it follows that the dose rate or production rate proportionally determines free testosterone, independent of SHBG.

@Gman86 presented some nice anecdotal evidence here. He made one change in his protocol, switching to exemestane from anastrozole. This knocked down his SHBG from 51 to 36 nMol/L. But total testosterone also dropped, and free testosterone remained essentially unchanged.

If mesterolone is increasing free testosterone at steady state then it would have to be through altering the metabolic clearance rate constant. So far I've seen no evidence in support of this.


I'm sure there are dozens, if not hundreds of such publications. But with these there is some danger of not seeing the forest for the trees. The simple analogies are meant to avoid that.

Click to expand...

Seagal said:

Are you using Minoxidil? It can also affect androgens.
I suspected it but there was no scientific evidence, just because it wasn't researched.

New Target for Minoxidil in the Treatment of Androgenetic Alopecia

To investigate the mechanism of minoxidil in treating androgenetic alopecia (AGA).The mechanism of action of minoxidil on AGA was first systematically investigated from the viewpoint of network pharmacology, including minoxidil-AGA target prediction, ...

www.ncbi.nlm.nih.gov

Click to expand...