The Myth of Testosterone Suspension (aqueous; or in oil [TNE], testosterone base) & Uncontrollable Estrogenicity (Increased E2) [Author: Type-IIx]

[Type-IIx]

The matter of testosterone base (as aqueous, water-based; or in oil vehicle, as Testosterone No Ester [TNE]) and changes to estradiol (E2) is one of much confusion.

In fact, before the availability of AI & SERM drugs, besides compound selection strategies aimed at moderate testosterone dosing & rational combination strategies (e.g., synergistic [1 + 1 > 2], complementary [1 + -1 = 0], & additive [1 + 1 = 2]) and tactics (e.g., manipulating administration schedules/frequencies to optimize efficacy/tolerability tradeoffs), the use of testosterone suspension during contest prep & even peak week where anabolics were maintained right up to the contest was a commonplace strategy to reduce fluid retention.

See Robert Kerr's 1982 book, "The Practical Use of Anabolic Steroids with Athletes..." Chapter 12:

If "making weight"... the aqueous testosterone... might be considered... Daily or every other day injections are used with no gain in the fluid weight. No one enjoys being injected on a daily basis so this medication is limited to the last week, two at most. As the solution is water-based, a very small caliber hypodermic needle...pain-free. If the daily injections are desired and recommended to the patient, I would probably recommend 100 to 200 mg. per day of the aqueous testosterone solution...

Indeed, bloodwork evidence supporting this rational use exists in the annals of this very forum. From Testosterone No Ester (TNE) PART 2...

At 2.5 - 3 h post-injection (50 mg testosterone base, oil vehicle; TNE)...Cmax (peak concentration) occurring between 1 - 2 h for most individuals:

Noteworthy Results: insignificant rise in estradiol (E2: 22.6 vs. 20.1 [base-line] pg/mL; no significant increase to HCT, Hb; LH & FSH remained normal).

Edited & Summarized by Type-IIx, for clarity, a statement relayed by the post author from a private medical consultant, explaining that:
1. Erythropoiesis: Erythrocyte (RBC; red blood cell) formation takes 7 days, so injecting a rapid source of testosterone would not cause the body to create as many RBCs as a longer ester testosterone formulation, such that the body would clear the single dose (TNE; 50 mg) before a full account of the production of RBC would occur, thereby maintaining normal RBC #, on short (< 1 w) time-frames & wide administration intervals.
2. Pharmacokinetics vs. Pharmacodynamics: Although the body does compensate for the increased level of testosterone, it's a longer process then the peak of the half life testosterone itself, and the rise in estrogen is more of an after-effect than something that will be perfectly coupled to by testosterone dose. Daily injections of TNE will superimpose estradiol elevations dose- & time- dependently; indeed, injecting as frequently as q9d (every nine days) may lead to superimposition (from the Tlast [max] PK data for aqueous testosterone suspension).

Further Reading from Type-IIx's Notes:
Andronaq; Sterotate; Virosterone (aqueous)
Pharmacokinetics

An aqueous suspension of testosterone crystals injected intramuscularly in doses of 20 mg. provides a satisfactory replacement therapy in male hypogonadism. The apparent period of effective supply of testosterone from each injection is from four to seven days. [64].

Biphasic delivery profile:

The early peak concentration of testosterone is attributed to absorption of testosterone in solution from the formulation after IM administration. The second and subsequent peaks are attributed to dissolution of testosterone from the solid material in the suspension with similar results being reported in humans (Misra, et al., 1997). [65].
0.15 mg/kg aqueous testosterone suspension (75 mg/mL) in horses; mean weight 534.1 kg (i.e., mean dose 80 mg)
t1/2 (half life): median 33.0 hr (39 hr terminal), min 16.3 hr, max 56.8 hr
Tmax: median 6.0 hr, min 1.0 hr, max 408 hr (appearing between 1 - 2 hr for most horses)
Cmax: median 646 pg/mL, min 302 pg/mL, max 1308 pg/mL
Tlast: median 336 hr, min 216 hr, max 672 hr
[65]

References
[64] SEVRINGHAUS, E. L., & SIKKEMA, S. (1946). THERAPY WITH AQUEOUS SUSPENSIONS OF TESTOSTERONE. The Journal of Clinical Endocrinology & Metabolism, 6(6), 415–419. doi:10.1210/jcem-6-6-415
[65] MOELLER, B. C., SAMS, R. A., GUINJAB-CAG, MAT, J., SZABO, N. J., COLAHAN, P., & STANLEY, S. D. (2011). An interlaboratory study of the pharmacokinetics of testosterone following intramuscular administration to Thoroughbred horses. Journal of Veterinary Pharmacology and Therapeutics, 34(6), 588–593. doi:10.1111/j.1365-2885.2011.01277.x

 

[RedSwingline]

First!

 

[readalot]

All of the early work with TNE. It's PK profile similar to TP.

Even copied all the pages of each paper into the thread for you light bedtime readers.

Testosterone (no ester) Suspension for Injection - Literature Review

Going to do a thread on what is often referred to as TNE (Testosterone No Ester) on here. This preparation would be crystalline testosterone in an aqueous suspension (e.g., Aquaviron). I'll see what I can find on pharmacokinetics as well. Building off of @madman 's post here...

www.excelmale.com

 

[klokke23]

So no significant changes after one injection of TNE? Crazy

 

[xrayphoton13]

I use compounded testosterone cream for trt. I guess this explains why even with my total t at 3200ng/dl I didn't need AI. My doc also said he doesn't see a rise in hematocrit with his patients on cream

 

[AlwaysHungry]

That’s very interesting ! As I’m pinning ED anyways on cycles.
Would the “gains” and benefits be the same as long ester testosterone?
Or the same and just more benefits ?

I ask this because with long ester testosterone if you pin ED your test levels I imagine would be through the roof 24/7
Versus suspension who has very short half life

 

[xrayphoton13]

That’s very interesting ! As I’m pinning ED anyways on cycles.
Would the “gains” and benefits be the same as long ester testosterone?
Or the same and just more benefits ?

I ask this because with long ester testosterone if you pin ED your test levels I imagine would be through the roof 24/7
Versus suspension who has very short half life

If you were asking me I'm honestly not sure. I've never done injections or even a cycle yet. When my total t was in the 3000s it was just my starter dose the doc put me on. When we ran bloods he was shocked. We had to cut the dose back

 

[Type-IIx]

That’s very interesting ! As I’m pinning ED anyways on cycles.
Would the “gains” and benefits be the same as long ester testosterone?
Or the same and just more benefits ?

I ask this because with long ester testosterone if you pin ED your test levels I imagine would be through the roof 24/7
Versus suspension who has very short half life

You might find this pertinent:

Anyone run MENT and tren together?

While your information sounds good on paper, you still lack the personal experience of using it. Good point. Personal experience with something is the only means to understanding it. This MENT Profile [link] might actually be of some value if I had decided, after performing my own balancing of...

thinksteroids.com

I do believe that you'll find that daily pinning even with medium-length esters (e.g., enanthate, cypionate, phenylpropionate, hexahydrobenzylcarbonate) does not, when plotted in a tool like steroidplotter, confer "smoothness" at all, but rather frequent "spiking." This does increase dose as fAUC, and therefore potency, but also reduces tolerability, particularly due to hematocrit, swelling/pain at the injection sites, etc.

At the end of the day, though, it basically boils down to your individual preference. If you use subcutaneous application, that makes a lot more sense, and should actually prove beneficial for those same side effects.

 

[readalot]

does not, when plotted in a tool like steroidplotter, confer "smoothness" at all, but rather frequent "spiking."

Those spikes are due to tools like SteroidPlotter not including absorption rate but only apparent elimination rate constant. I'll skip all the long winded flip flop kinetics stuff.

More realistic first order absorption plus elimination model:

Same AUC but peaks get clipped.

Low Dose Sustanon250 Cycle?

Same dosing schedule modeled with either first order elimination or first order absorption plus elimination: Adding the additional realism of 4-6 hr absorption half life lops off the pronounced peak and slightly raises the trough on an injectable with ~5 day elimination half life. Now in...

forums.t-nation.com

More data and parameters:

Steroid Plotter Correct? Max Serum Test Release When Time = 0

Table 2: Example of use: Input for spreadsheet: Examples use apparent absorption half life of 8 hr and elimination half life ~4.5 d for test cyp. The original crappy elimination only models with instantaneous absorption finally got replaced with the refined absorption + elimination...

forums.t-nation.com

 

[Type-IIx]

Those spikes are due to tools like SteroidPlotter not including absorption rate but only apparent elimination rate constant. I'll skip all the long winded flip flop kinetics stuff.

More realistic first order absorption plus elimination model:

Same AUC but peaks get clipped.
View attachment 276439
View attachment 276440

Low Dose Sustanon250 Cycle?

Same dosing schedule modeled with either first order elimination or first order absorption plus elimination: Adding the additional realism of 4-6 hr absorption half life lops off the pronounced peak and slightly raises the trough on an injectable with ~5 day elimination half life. Now in...

forums.t-nation.com

More data and parameters:

Steroid Plotter Correct? Max Serum Test Release When Time = 0

Table 2: Example of use: Input for spreadsheet: Examples use apparent absorption half life of 8 hr and elimination half life ~4.5 d for test cyp. The original crappy elimination only models with instantaneous absorption finally got replaced with the refined absorption + elimination...

forums.t-nation.com

If you say so.

Steroid Plotter just plots y = the sum of 1/(2^(t/h)) across specified intervals.

Whatever smoothening seems to be occurring there is a result of some transformation function.

It's all estimates anyway.

And yet, still, the points remain that I raised in Anyone run MENT and tren together?

What point were you trying to make? That, ooo, pretty, smoothies not spikies?

 

[readalot]

If you say so.

Steroid Plotter just plots y = the sum of 1/(2^(t/h)) across specified intervals.

Whatever smoothening seems to be occurring there is a result of some transformation function.

It's all estimates anyway.

And yet, still, the points remain that I raised in Anyone run MENT and tren together?

What point were you trying to make? That, ooo, pretty, smoothies not spikies?

Your 2nd steroidplotter graph is not consistent with the figure label. You may want to check those. AUC will be the same for either case (350 e7d or 50 ed).

 

[Type-IIx]

Your 2nd steroidplotter graph is not consistent with the figure label. You may want to check those. AUC will be the same for either case (350 e7d or 50 ed).

It's "not consistent?" What am I, misrepresenting it? Plot it yourself. You know what? Don't bro. Just get fuckin' lost, unless you can commit yourself to working on your serious unlikeability.

 

[readalot]

Just get fuckin' lost

Same to you. Your opinion of my likeablity is irrelevant.

I see I made a mistake and assumed both plots were same ester. That was my bad assuming you were making a valid comparison of same amount of tren per week. Why would you give an example of tren A vs tren E for the same mg/week? Obviously you know the former is 86% tren and the later is 70%. Way to bait and switch that dude on molecular weights and tren composition. If you make the proper comparison (350 mg/week TA vs 430 mg/week TE) then of course they will have same area under curve (law of mass action). And you won't even acknowledge the huge overshoot steroid plotter makes ignoring the absorption term.

What was my point? Serum tren or test levels and release rates are continuous functions with continuous derivatives. Your comments about Tmax (feel free to click the link and see its defintion in a first order absorption plus elimination model) are meaningless without considering this fact. But go ahead with your smart ass comment about spikies vs smoothies.

4. Equations for tmax and t1/2​

The equation for calculating t max (peak plasma time):

= ln ( / ) / (−)

= 2.303 log ( / )/ (−)

On the other hand, the equation for calculating t½:

t½ = 0.693 × (Vd /CL)

Where, Vd = Volume of distribution and CL = Clearance.

Fragile, are we? You loved crapping in my thread but get hostile when someone offers instructive info in your own. So no, your point in the other thread does not stand. Your comparison was misleading.

Try lowering your dosing.

 

[readalot]

Whatever smoothening seems to be occurring there is a result of some transformation function.

Application of Pharmacokinetic-Pharmacodynamic Modeling in Drug Delivery: Development and Challenges

With the advancement of technology, drug delivery systems and molecules with more complex architecture are developed. As a result, the drug absorption and disposition processes after administration of these drug delivery systems and engineered molecules ...

www.ncbi.nlm.nih.gov

Flip-Flop Kinetics A popular formulation approach is to extend the release of drug from the delivery system to reduce the dosing frequency and improve patient compliance (Stege et al., 1996; Jadhav et al., 2006). When the absorption process is much slower than the elimination process, the apparent half-life significantly increases due to the slow absorption step, resulting in flip-flop kinetics (Davis, 2018). For instance, in a one-compartment model with first-order absorption and elimination (Figure 2), when absorption rate ka is much smaller than the elimination rate kel (derived by CL/V), resulting in the flip-flop phenomenon. A schematic of flip-flop kinetics in Figure 3 shows the simulated PK profile of a drug upon IV and extravascular administration. With a rapid absorption (ka > kel), the terminal slope of the concentration-time profile is similar to that after IV administration route, reflecting the kel. However, when drug absorption is slower than the elimination (k a < k el), the absorption process becomes the rate-limiting step. The downward concentration-time curve is less steep and reflects the ka, while the upward curve reflects the elimination process, kel.

Pharmacokinetics are your friend.

 

[Type-IIx]

Application of Pharmacokinetic-Pharmacodynamic Modeling in Drug Delivery: Development and Challenges

With the advancement of technology, drug delivery systems and molecules with more complex architecture are developed. As a result, the drug absorption and disposition processes after administration of these drug delivery systems and engineered molecules ...

www.ncbi.nlm.nih.gov

Pharmacokinetics are your friend.

Yeah, flip-flop pharmacokinetics is a topic I want to delve into with you on a steroid board.

Same to you. Your opinion of my likeablity is irrelevant.

I see I made a mistake and assumed both plots were same ester. That was my bad assuming you were making a valid comparison of same amount of tren per week. Why would you give an example of tren A vs tren E for the same mg/week? Obviously you know the former is 86% tren and the later is 70%. Way to bait and switch that dude on molecular weights and tren composition. If you make the proper comparison (350 mg/week TA vs 430 mg/week TE) then of course they will have same area under curve (law of mass action). And you won't even acknowledge the huge overshoot steroid plotter makes ignoring the absorption term.

What was my point? Serum tren or test levels and release rates are continuous functions with continuous derivatives. Your comments about Tmax (feel free to click the link and see its defintion in a first order absorption plus elimination model) are meaningless without considering this fact. But go ahead with your smart ass comment about spikies vs smoothies.




Fragile, are we? You loved crapping in my thread but get hostile when someone offers instructive info in your own. So no, your point in the other thread does not stand. Your comparison was misleading.

Try lowering your dosing.

I've extended you so much patience, but do you know why, basically, nobody likes you? Because you're here to try to prove how clever you are (you're not) and how dumb everyone else is.

Try the whole fist.

 

[baxter0312]

If you were asking me I'm honestly not sure. I've never done injections or even a cycle yet. When my total t was in the 3000s it was just my starter dose the doc put me on. When we ran bloods he was shocked. We had to cut the dose back

Bro, how much of that cream are you using?

 

[Dirthand]

So I am not following... is it OK or not ok to pin long esters daily?

 

[gburdell]

Bro, how much of that cream are you using?

Evidently all of it.