New thoughts on AI

[Gman86]

It’s too early to tell, but seems like short ester testosterone like creams and testosterone propionate, administered frequently, might be the future of TRT.

May very well be but unfortunately it will never be mainstream as a large percentage of men would not be comfortable injecting daily.

The combination of an injectable and daily application of a cream to ones protocol may very well benefit some but definitely is not needed for all.

Regardless of daily propionate possibly providing better results for some many do just fine injecting the longer acting esters daily.

Hope you understand that transdermal testosterone whether gel/cream is not esterified.

Even when injecting daily regardless of the ester used whether propionate, enanthate or cypionate none will result in mimicking the 24 hr circadian rhythm of endogenous testosterone of a healthy young male only the patch or transdermal (once daily application) would most closely mimic this.

Testosterone propionate has been shown to elevated blood levels for up to 36 hrs before declining so if anything when injecting prop daily you will get a quicker spike compared to enanthate/cypionate but levels are not going to decline within the first 24 hrs....so much for

Oh very interesting. Didn’t realize testosterone cream was not esterfied. And thanks for the peak time info on test prop. Makes sense, considering some do well injecting it EOD.

But I completely agree with everything you just said. Everyone’s different, and we just have to figure out what works best for us as individuals. Just nice to know there’s another option out there that seems to be a nice middle ground between test cyp/enanthate and creams.

To be honest, the biggest thing that intrigues me about prop is the fact that after a dosage change, I can get labs done around the 20 day mark, opposed to having to wait at least 6 weeks with cypionate/ enanthate. This would speed up the dialing in process drastically.

 

[madman]

William Llewellyn is well known and has provided the most valuable information regarding testosterone/AAS.


He has been on the forum.








William is an accomplished researcher and lecturer in the field of human performance enhancement, and a longtime monthly columnist for Muscular Development Magazine. He is also a long supporter of the harm reduction community, and currently holds the position of honorary lecturer at Liverpool John Moores University in the UK. For information on having William speak at your event, or how you can support harm reduction efforts in your area, please Contact Us.




Testosterone Propionate - Anabolic.org




Description:
Testosterone propionate is a commonly manufactured injectable form of the primary male androgen testosterone. The added propionate ester will slow the rate in which testosterone is released from the injection site, but only for a few days. Testosterone propionate is, therefore, comparatively much faster-acting than other testosterone esters such as cypionate or enanthate, and requires a much more frequent dosing schedule. By most accounts testosterone propionate is an older and cruder form of injectable testosterone, made obsolete by the slower-acting and more comfortable esters that were developed subsequent to it. Still, those who are not bothered by the frequent injection schedule find testosterone propionate every bit as acceptable. As an injectable testosterone, it is a powerful mass-building drug, capable of producing rapid gains in both muscle size and strength.


History:
Testosterone propionate was first described in 1935, during a series of experiments that set out to increase the therapeutic usefulness of testosterone by slowing its release into the bloodstream.566 Two years later, Schering AG in Germany would introduce the first testosterone propionate product under the brand name Testoviron®. Propionate was also the first commercially available injectable ester of testosterone on the U.S. prescription drug market, and remained the dominant form of testosterone globally before 1960. Back during the early 1950’s, for example, when steroids were first being experimented with by small numbers of American athletes, the only readily available anabolic/androgenic steroids were methyltestosterone, testosterone propionate, and testosterone suspension. Interesting enough, during this time testosterone propionate was also available in orally administered (Buccal) preparations, but they disappeared from the U.S. market during the 1980’s.


Early prescribing guidelines for testosterone propionate called for a number of therapeutic uses. It was mainly applied to cases of male androgen insufficiency, and those issues normally surrounding low testosterone levels such as reduced sex drive and impotence in adults, and cryptorchidism (undescended testicles) in teenagers and young adults. But it also had such other uses as treating menopause, menorrhagia (heavy menstrual bleeding), menstrual tension, chronic cystic mastitis (fibrocystic breasts), endometriosis, and excessive lactation, covering a wide range of situations in which the male hormone testosterone was being applied to female patients. Over the years these wide guidelines were narrowed by the U.S. Food & Drug Administration, however, and by the 1980’s, testosterone propionate was being largely applied only to male patients.


Testosterone propionate has a long history of availability in the U.S. and abroad, and remains a very common form of testosterone on the global market to this day. It must be emphasized, however, that its ability to remain on the market is more a product of history than unique application. Testosterone propionate was the first acceptable ester of testosterone, and consequently has many decades of history as a useable therapeutic agent. Many companies have sold it for decades now, and so long as it is still in demand will continue to do so. But other (more modern) forms of testosterone such as enanthate and cypionate are much more popular today, as they are much slower-acting still, and allow for far more comfortable administration schedules. Testosterone propionate is still approved for sale in the United States, although its ultimate market future here remains questionable.


Bodybuilders commonly consider propionate to be the mildest testosterone ester, and the preferred form of this hormone for dieting/cutting phases of training. Some will go so far as to say that propionate will harden the physique, while giving the user less water and fat retention than one typically expects to see with a testosterone like enanthate, cypionate or Sustanon. Realistically, however, these advantages do not hold up to close scrutiny. The propionate ester is actually removed before the testosterone it carries is active in the body, and ultimately has little effect outside of slowing steroid release. It all really boils down to how much testosterone you are getting into your blood with each particular esterified compound. Otherwise, there are no real functional differences between them.



Structural Characteristics:
Testosterone propionate is a modified form of testosterone, where a carboxylic acid ester (propionic acid) has been attached to the 17-beta hydroxyl group. Esterified forms of testosterone are less polar than free testosterone, and are absorbed more slowly from the area of injection. Once in the bloodstream, the ester is removed to yield free (active) testosterone. Esterified forms of testosterone are designed to prolong the window of therapeutic effect following administration, allowing for a less frequent injection schedule compared to injections of free (unesterified) steroid. The half-life of testosterone propionate is approximately two days after injection.

Figure 1. Pharmacokinetics of 25 mg labeled testosterone propionate injection. Source: Pharmacokinetic properties of testosterone propionate in normal men. Fujioka M, Shinohara Y,Baba S. et.Al. J Clin Endocrinol Metab 63 (1986):1361- 4

 

[madman]

Oh very interesting. Didn’t realize testosterone cream was not esterfied. And thanks for the peak time info on test prop. Makes sense, considering some do well injecting it EOD.

But I completely agree with everything you just said. Everyone’s different, and we just have to figure out what works best for us as individuals. Just nice to know there’s another option out there that seems to be a nice middle ground between test cyp/enanthate and creams.

To be honest, the biggest thing that intrigues me about prop is the fact that after a dosage change, I can get labs done around the 20 day mark, opposed to having to wait at least 6 weeks with cypionate/ enanthate. This would speed up the dialing in process drastically.

Pharmacokinetic Properties of Testosterone Propionate in Normal Men (1986)
MINORU FUJIOKA, YOSHIHIKO SHINOHARA, SHIGEO BABA, MINORU IRIE, AND KAZUKO INOUE




ABSTRACT. The pharmacokinetic characteristics of testosterone propionate were studied in normal men after a single im dose of 25 mg testosterone propionate-19,19,19-d3; Plasma levels of testosterone propionate-19,19,19-d3, its active metabolite testosterone-19,19,19-d3, and endogenous testosterone were measured by gas chromatography-mass spectrometry. Testosterone propionate-19,19, 19-d3 was gradually transferred from the im injection site to the systemic circulation. The plasma levels of testosterone propionate-19,19,19-d3 were maintained at 2-4 ng/ ml between 3 and 36 h after administration. Plasma testosterone-19,19,19-d3 levels were maintained above the physiological testosterone level for 48 h, while plasma levels of endogenous testosterone changed little. (j Clin Endocrinol Metab 63: 1361, 1986)

 

[stx359]

That line of thinking has not been really well received on this forum and those individuals that are on that "roundtable", the youtube doctors, have been well criticized here. In fact they don't come near this forum or have otherwise been banned.

You need to spend some time with the search feature...I doubt that there is going to be any new discussion on this allowed.

I was confused by this. No new discussion allowed? Does this board ban free speech? I don't follow the "youtube docs" as I find them rather obnoxious but I thought Nelson himself was skeptical of aggressive E2 management with AIs.

When you "spend time with the search feature" on here you find countless stories of guys who crashed their E2 with aggressive AI use. The answer has to be that E2 management should vary from individual to individual. Guys that have decently high SHBG have much more leeway than those that don't. The test to use is not sensitive E2 but free E2. Stifling discussion of it seems like a stupid way to address the issue. Surely you were being facetious.

 

[Gman86]

I was confused by this. No new discussion allowed? Does this board ban free speech? I don't follow the "youtube docs" as I find them rather obnoxious but I thought Nelson himself was skeptical of aggressive E2 management with AIs.

When you "spend time with the search feature" on here you find countless stories of guys who crashed their E2 with aggressive AI use. The answer has to be that E2 management should vary from individual to individual. Guys that have decently high SHBG have much more leeway than those that don't. The test to use is not sensitive E2 but free E2. Stifling discussion of it seems like a stupid way to address the issue. Surely you were being facetious.

You’re spot on my friend. Free E2 bypasses the need to even know SHBG level (still needed to know ideal injection frequency), total E2 or Albumin level. It takes the guess work/ speculation right out of the equation. I personally, like to have my free E2, total standard E2, and total sensitive E2, but that’s only because my labs are covered by insurance, and having more info can only help, not hurt. But free E2 is the only true marker for estrogen that matters, imo, and for most men, you want to try and stay mid-high in the range, opposed to the low end.

 

[Vince Carter]

Does this board ban free speech?

There are exactly 0 forums where you have free speech.

 

[Gman86]

Here are how my total E2 numbers compare to free E2, so you can kind of see where someone’s free E2 sits, while having my SHBG and Albumin levels, compared to my total E2 in each specific bloodwork.

6-16-17
E2 NOT Sensitive - 71
E2 Free - 1.88 (0.2-1.5)
SHBG 44 (10-50)
Albumin - 4.4g/dL (3.6-5.1)

8-15-17
E2 Sensitive - 8
E2 NOT Sensitive - 13
E2 Free - 0.28 (0.2-1.5)
SHBG 51 (10-50)
Albumin - 4.6g/dL (3.6-5.1)

12-13-17
E2 Sensitive - 9
E2 NOT Sensitive - 13
E2 Free - 0.28 (0.2-1.5)
SHBG 36 (10-50)
Albumin - 4.4g/dL (3.6-5.1)

7-9-18
E2 Sensitive - 46
E2 NOT Sensitive - 27
E2 Free - 0.58 (0.2-1.5)
SHBG 47 (10-50)
Albumin - 4.6g/dL (3.6-5.1)

8-24-18
E2 Sensitive - 57
E2 NOT Sensitive - 56
E2 Free - 1.35 (0.2-1.5)
SHBG 41 (10-50)
Albumin - 4.3g/dL (3.6-5.1)

10-23-18
E2 Sensitive - 58
E2 NOT Sensitive - 68
E2 Free - 1.48 (0.2-1.5)
SHBG 44 (10-50)
Albumin - 4.6g/dL (3.6-5.1)

12-6-18
E2 Sensitive - 10
E2 NOT Sensitive - 15
E2 Free - 0.33 (0.2-1.5)
SHBG 45 (10-50)
Albumin - 4.7g/dL (3.6-5.1)

1-25-19
E2 Sensitive - 29
E2 NOT Sensitive - 27
E2 Free - 0.67 (0.2-1.5)
SHBG 40 (10-50)
Albumin - 4.5g/dL (3.6-5.1)

This last set of labs is a perfect example of why free E2 is so important. A total sensitive E2 of 29 might seem pretty ideal for some men, but as you can see, my free E2 is still too low in the range, imo. I’m currently having low penile sensitivity, low libido, and trouble reaching orgasm with a partner.

 

[CoastWatcher]

As a senior moderator, I can assure all members that banning is the last thing anyone wants to do. Nonetheless, there is a code of conduct here that Nelson has set forth and - since it's his forum - we ask all to adhere to it.

That said, enough with the "Sieg Heil," please.

Many thanks.

 

[Gman86]

Firstly, I'm not sure why anyone would get banned for expressing an honest opinion borne out of experience, that's just Nazi thinking. I find that giving advice here is hard unless one knows the medical history involved, including the reasoning behind the TRT/juicing. Personally, I don't use either AI or HCG, have great results, no side effects and feel great. I workout every day, (boxing/kick-boxing/weights/Isometrics). I'm 63 and 120lbs. If this gets me banned, Sieg Heil! Otherwise, namaste.

What is your testosterone dose and frequency, if you don’t mind me asking. Glad you’re feeling so great.

 

[Cataceous]

...
Even when injecting daily regardless of the ester used whether propionate, enanthate or cypionate none will result in mimicking the 24 hr circadian rhythm of endogenous testosterone of a healthy young male only the patch or transdermal (once daily application) would most closely mimic this.

Testosterone propionate has been shown to elevated blood levels for up to 36 hrs before declining so if anything when injecting prop daily you will get a quicker spike compared to enanthate/cypionate but levels are not going to decline within the first 24 hrs....so much for

I'm going to respectfully disagree with this. Propionate cannot build up indefinitely. After stabilization there will be a daily peak and pre-injection trough. If you time the injections right you might be able to hit your peak at the physiologically-normal time of 8 am, thus mimicking a typical diurnal rhythm. Some of us absorb transdermal testosterone very inconsistently and thus could never achieve appropriate diurnal variation with this form of TRT.

 

[Vince Carter]

People get this lost in the daily injection discussion, there is still a peak and a trough in play.

After stabilization there will be a daily peak and pre-injection trough.

 

[sokaiya]

I take 25mg of testostosterone enanthate EOD and i do not use an AI. My E2 usually sits around 40. I also (for me personally) don't believe in using HCG. HCG would cause my E2 to increase a lot and other side effects as well. I feel great and my blood work is on point every single month.

 

[madman]

I'm going to respectfully disagree with this. Propionate cannot build up indefinitely. After stabilization there will be a daily peak and pre-injection trough. If you time the injections right you might be able to hit your peak at the physiologically-normal time of 8 am, thus mimicking a typical diurnal rhythm. Some of us absorb transdermal testosterone very inconsistently and thus could never achieve appropriate diurnal variation with this form of TRT.

Of course there is still going to be a daily peak/trough with prop but understand that even when using prop daily the troughs are going to be minimal and are in no way comparable to the the 24 hr circadian rhythm of a healthy young male endogenous testosterone levels.

Within 2 hrs of injecting prop T levels are increasing and peak at 12-14 hr and stay elevated for up to 24 hrs before declining and even though there is going to be fluctuations during those 24 hrs there is not going to be a drastic drop in T levels during that time.....compared to injecting prop EOD where there will be a much bigger difference between peak/trough levels as due to the pharmacokinetics of propionate levels decline much more rapidly 24-36 hrs post injection.

Naturally endogenous levels peak in the early am and than decline in the late afternoon/early evening (trough) and there can be up to a 30-40% difference between peak/trough levels.

Average healthy young males have a TT of 600-800 ng/dL at peak and T levels are much lower at trough on a daily basis.

When on trt regardless of ester used whether injecting daily most men are running 1000+ TT levels and although there is still a peak/trough even with daily most still have a trough level well into the high end of the physiological range as when injecting daily the difference between peak/trough is not extreme as daily results in the most stable levels although there are still fluctuations.

So even with daily prop.....sure you are getting the benefit of the earlier peak compared to enanthate/cypionate but you are in no way mimicking some form of natural diurnal rhythm.

All that said as we know not only dose of T/injection frequency effect the difference between peak/trough levels but most importantly ones SHBG.

 

[Cataceous]

Of course there is still going to be a daily peak/trough with prop but understand that even when using prop daily the troughs are going to be minimal and are in no way comparable to the the 24 hr circadian rhythm of a healthy young male endogenous testosterone levels.

Within 2 hrs of injecting prop T levels are increasing and peak at 12-14 hr and stay elevated for up to 24 hrs before declining and even though there is going to be fluctuations during those 24 hrs there is not going to be a drastic drop in T levels during that time.....compared to injecting prop EOD where there will be a much bigger difference between peak/trough levels as due to the pharmacokinetics of propionate levels decline much more rapidly 24-36 hrs post injection.
...

Variations with T propionate can be pretty significant, certainly into the range of a young guy's diurnal variation. For example, using SteroidCalc.com we see that at steady state peaks are more than 50% higher than troughs.

The model used by this site may be a little simplistic, assuming a linear rise and then an exponential decay w/0.8-day half life. I will post a more realistic version as soon as I have a chance to run the simulation. I will bet that the realistic version does not show a sudden drop-off near the end of the 24-hour cycle. My tests with enanthate simulations suggest that the rise is the steep part of the curve. The timing and shape of the curve may not be a great match for the more sinusoidal natural variation, but the transdermal curves I've seen are no better, and maybe worse.

 

[Cataceous]

...
All that said as we know not only dose of T/injection frequency effect the difference between peak/trough levels but most importantly ones SHBG.

I'm very interested in your thoughts on specifically how SHBG affects the curves of serum testosterone, either as impulse response or in steady state.

 

[madman]

I'm very interested in your thoughts on specifically how SHBG affects the curves of serum testosterone, either as impulse response or in steady state.

I would say it comes down to metabolic clearance rates determined by ones (SHBG/hepatic blood flow) between individuals.

Men with lower SHBG would notice a more drastic drop in T levels between peak/trough.

SHBG not only buffers serum testosterone levels but also decreases hepatic degradation.

As we know lower SHBG men will have a larger variation between peak/trough levels and tend to do much better injecting lower doses more frequently but even than I would say their peak/trough would me more drastic even on daily injections as oppose to one with normal SHBG.

The only true way to know how said dose of T used/injection frequency and choice of ester used will effect ones TT/FT/E2 and DHT levels would be to have blood work done frequently post injection to truly see how levels look 12/24/36/48 hrs and so on which is not feasible for most if we want to look at blood levels at many time points.

We can sit here and say peak/trough this and that but in the end as we know every individual is different and many factors come into play on what peak/trough levels one would achieve on said protocol (dose/injection frequency/ester used).

Blood work done frequently is the only way.

 

[madman]

Variations with T propionate can be pretty significant, certainly into the range of a young guy's diurnal variation. For example, using SteroidCalc.com we see that at steady state peaks are more than 50% higher than troughs.
View attachment 6898
The model used by this site may be a little simplistic, assuming a linear rise and then an exponential decay w/0.8-day half life. I will post a more realistic version as soon as I have a chance to run the simulation. I will bet that the realistic version does not show a sudden drop-off near the end of the 24-hour cycle. My tests with enanthate simulations suggest that the rise is the steep part of the curve. The timing and shape of the curve may not be a great match for the more sinusoidal natural variation, but the transdermal curves I've seen are no better, and maybe worse.

Circulating natural endogenous testosterone levels are also dynamic and feature distinct circhoral and diurnal rhythms.

I would be more interested in seeing blood work of men on daily prop 12 hr and 24 hr post injection.

Also the pharmacokinetics and pharmacodynamics of androgen esters are not only determined by the ester side-chain length but also the volume of oil vehicle and site of injection.

 

[Cataceous]

...
As we know lower SHBG men will have a larger variation between peak/trough levels and tend to do much better injecting lower doses more frequently but even than I would say their peak/trough would me more drastic even on daily injections as oppose to one with normal SHBG.
...

I'm having problems with this particular bit of conventional wisdom. First, are there any controlled studies demonstrating the effect? And second, what is the theoretical basis? From what I can see, the effective MCR influenced by SHBG ties into a half life on the order of at most a few hours. This has very little impact on the relatively long apparent half lives of the testosterone esters. Instead, everything is scaled accordingly. That is, double the MCR and get half the serum testosterone—but the peaks are still the same fraction of the troughs. What am I missing?

 

[n2turbo2]

I take 25mg of testostosterone enanthate EOD and i do not use an AI. My E2 usually sits around 40. I also (for me personally) don't believe in using HCG. HCG would cause my E2 to increase a lot and other side effects as well. I feel great and my blood work is on point every single month.

What side effects did you have on HCG? I am dropping my HCG to. I think the HCG is driving my E2 up to. They should start people off on test, without a ai. Then test E2. I know now if i dont use a Ai my e2 goes up to 160 on test and HCG. Now im doing subq 3 times a week and dropping HCG. We will see what happens.

 

[Gianluca]

In the past when I needed an AI to combat side effects it was from (i) long esters (ii) infrequent injections (iii) HCG (iv) DHEA (vi) too much body fat.

I feel best with frequent injections with short ester and nothing else.

I neither take AI, nor HCG, nor DHEA, nor Pregnenolone anymore.

Tested it all and for me doesn't improve the experience that I get from short ester applied frequently.

When I take long ester or HCG it's a different ballgame and I need at least an AI to feel half way good plus pregnenolone to combat brainfog.

If I still had side effects from high E2, I would try taking pregnenolone over an AI. It seems to reduce E2 for me via the progesterone pathway. But then with short ester and frequent injections I don't get there in the first place.

I have come to the conclusion if one needs AI to combat side effects, the protocol is not optimal for the person. Instead of trying to fix a suboptimal protocol with AI, the smarter move seems to be finding a better protocol. The most effective change I have found is using a short ester.

Very nice, I had the same thought, at some point of my TRT I started to develop more and more E2 symptoms, I was using AI, but when I then started a bit of Hydrocortisone my E2 symptoms actually disappeared and I believed for leaving more Progesterone available. I use now also Pregnelonone and I'm on SubQ and 0 E2 symptoms, and no AI.

That is why I stress anyone to pay attention to Pregnelonone, in some people that will drop during TRT, and it could cause troubles here and there