Pharmacokinetic Profile of Testosterone Suspension: A Case Study

[Cataceous]

Thanks for follow-up Cat. Why not substitute TNE oil-based for TS since the particles are dissolved?

With the caveat that this is all speculation, I think that TNE in oil is likely to have a different character. I'm guessing it is between Natesto and oral testosterone in terms of half-life. It could be viable, but might require more "fill-in" testosterone after it dissipates. That is, overnight could be problematic if natural production stays low. In contrast, the apparent two-phased nature of TS means that the larger particles are supplying a low, steady background level, while the smaller particles drive significant, short-lived post-injection spikes. I'm betting these spikes are helping to drive the good results. Perhaps the spikes somewhat mirror the natural pulsatile delivery of testosterone. I find some support in this research, which is implying fairly large transient increases in endogenous testosterone. In any case, I suspect that the short phase of TS is faster-acting than TNE in oil, due to the hydrophobic nature of the oil.

I noticed a slower CNS spike with TNE for what that is worth. Not sure if CNS spike is proxy for T spike, but TNE was noticeably slower to hit than TS.

This aligns with my speculation.

I am going to try adding Kisspeptin-10 this week to my low dose regimen of straight TE. No pulsing, just 2-3x per week bolus-style.

I'll be interested in seeing your report on this.

 

[Willyt]

In contrast, the apparent two-phased nature of TS means that the larger particles are supplying a low, steady background level, while the smaller particles drive significant, short-lived post-injection spikes. I'm betting these spikes are helping to drive the good results. Perhaps the spikes somewhat mirror the natural pulsatile delivery of testosterone. I find some support in this research, which is implying fairly large transient increases in endogenous testosterone. In any case, I suspect that the short phase of TS is faster-acting than TNE in oil, due to the hydrophobic nature of the oil.

Ok thanks I now understand your comment about two phases with TS

 

[joikd]

Forgive me for not quite understanding, but is the goal to use TS to supplement natural T production without shutting down and also to mimic the natural daily fluctuation of T? And for this to be a long-term TRT protocol? If so, would that mean there would be no need for HCG?

I homebrew my own T (only for TRT purposes). I am currently using testosterone phenylpropionate daily (based on your posts, Cataceous) and HCG twice weekly. So, if going the TS route might be better, it's something I'm willing to brew up and give a try.

 

[Cataceous]

Forgive me for not quite understanding, but is the goal to use TS to supplement natural T production without shutting down and also to mimic the natural daily fluctuation of T? And for this to be a long-term TRT protocol? If so, would that mean there would be no need for HCG?
...

These were basically the original goals: to obtain an injectable equivalent to Natesto, which would have better precision in dosing. However, to emulate Natesto the testosterone must be delivered in a single fast-acting phase. This is what's needed to maintain reasonable HPTA activity without the use of ancillaries (such as enclomiphene, gonadorelin, etc). Though not definitive, the evidence is pointing against this scenario for TS because of a possible long-acting secondary phase.

The water-based testosterone solution I discussed above might still be a candidate. But the unexceptional subjective results have thus far deterred me from attempting a prolonged evaluation. Perhaps in these shorter time frames natural production hasn't recovered enough to fill in the gaps between doses.

In contrast, the TS protocol is providing very good results—not quite as over-the-top as occasional brief honeymoon periods in the past, but preferred because the results are increasingly looking to be sustainable.

I homebrew my own T (only for TRT purposes). I am currently using testosterone phenylpropionate daily (based on your posts, Cataceous) and HCG twice weekly. So, if going the TS route might be better, it's something I'm willing to brew up and give a try.

My understanding is that home-brewing of TS is not a trivial undertaking. First you have to ensure the particle sizes are small enough, which may require specialized milling equipment. Then you have to ensure reasonable stability. I seem to have learned the hard way that unwanted particle aggregation has the potential to ruin the pharmacokinetic profile.

Given the low doses involved, the cost of using the Pharmacom TS brand is pretty reasonable, even if you pay a premium for domestic shipping.

I did demonstrate that it is possible, though not necessarily practical, to ditch the hCG in a protocol like yours. A substantial benefit of the TS versus my enanthate/propionate or your phenypropionate is the ability to drop the SERM. This is undoubtedly dose-dependent. There's surely a balance required between the amount of gonadorelin needed for LH/FSH production and the amount of exogenous testosterone you use. The pharmacokinetics of the exogenous T is also a factor.

Alternatively, experimenting with water-based testosterone solutions is cheap and easy once you have testosterone powder. Ideally you'd use less benzyl alcohol than I did in the formula above, but I'm not sure the solubility can be maintained.

 

[Guided_by_Voices]

These were basically the original goals: to obtain an injectable equivalent to Natesto, which would have better precision in dosing. However, to emulate Natesto the testosterone must be delivered in a single fast-acting phase. This is what's needed to maintain reasonable HPTA activity without the use of ancillaries (such as enclomiphene, gonadorelin, etc). Though not definitive, the evidence is pointing against this scenario for TS because of a possible long-acting secondary phase.

The water-based testosterone solution I discussed above might still be a candidate. But the unexceptional subjective results have thus far deterred me from attempting a prolonged evaluation. Perhaps in these shorter time frames natural production hasn't recovered enough to fill in the gaps between doses.

In contrast, the TS protocol is providing very good results—not quite as over-the-top as occasional brief honeymoon periods in the past, but preferred because the results are increasingly looking to be sustainable.



My understanding is that home-brewing of TS is not a trivial undertaking. First you have to ensure the particle sizes are small enough, which may require specialized milling equipment. Then you have to ensure reasonable stability. I seem to have learned the hard way that unwanted particle aggregation has the potential to ruin the pharmacokinetic profile.

Given the low doses involved, the cost of using the Pharmacom TS brand is pretty reasonable, even if you pay a premium for domestic shipping.

I did demonstrate that it is possible, though not necessarily practical, to ditch the hCG in a protocol like yours. A substantial benefit of the TS versus my enanthate/propionate or your phenypropionate is the ability to drop the SERM. This is undoubtedly dose-dependent. There's surely a balance required between the amount of gonadorelin needed for LH/FSH production and the amount of exogenous testosterone you use. The pharmacokinetics of the exogenous T is also a factor.

Alternatively, experimenting with water-based testosterone solutions is cheap and easy once you have testosterone powder. Ideally you'd use less benzyl alcohol than I did in the formula above, but I'm not sure the solubility can be maintained.

What is your objection to SERMs?

 

[Cataceous]

What is your objection to SERMs?

The possible interactions with non-target receptors, uncertain long-term safety and lack of endogenous origins for many of them. Anecdotally the SERM success stories are fairly rare, whereas it's common to see guys reporting good numbers but not great subjective results. Now this is in part a result of reporting bias, where happy guys are much less likely to be on the forums complaining about problems. However, if I'm remembering correctly, the FDA was initially loathe to clear enclomiphene for similar reasons.

Personally I have the sense that encomiphene was preventing me from getting the best results. It was still a significant improvement to regain some HPTA activity under TRT with the help of enclomiphene and gonadorelin, but now that I can contrast the experience with the gonadorelin/TS protocol, I feel it was lacking. It's not a completely neutral comparison, because as I've discussed here, the TS replacing the enanthate/propionate blend has unique pharmacokinetics that likely contribute to the results.

 

[madman]

Forgive me for not quite understanding, but is the goal to use TS to supplement natural T production without shutting down and also to mimic the natural daily fluctuation of T? And for this to be a long-term TRT protocol? If so, would that mean there would be no need for HCG?

I homebrew my own T (only for TRT purposes). I am currently using testosterone phenylpropionate daily (based on your posts, Cataceous) and HCG twice weekly. So, if going the TS route might be better, it's something I'm willing to brew up and give a try.

The doses of TS he is taking are well below what anyone would use for sole TRT.

Even then injecting once daily would never mimic the PK of nasal T gel which has been shown to have limited impact on suppression of the HPG-axis as T max is achieved within an hour which results in a very short-lived peak and levels return back to baseline 4-6 hrs later.

Natesto is dosed 2-3X daily and there is a significant trough time over a 24 hr period.

It us an ultra fast acting (peak--->trough) formulation!

As I stated in a previous thread although TS is unesterified the crystals of T may very well behave like small implants being more slowly absorbed from the tissues which would have an impact on the half-life.

Daily injections of TS using doses that would allow one to achieve a high enough peak/trough would have a stronger impact on suppression HPG-axis.

Natty rise in endogenous T happens gradually overnight and highest levels are achieved in the early AM.

You could never mimic this with daily TS.

The closest you could get to mimicking the natural 24hr circadian rhythm of a healthy young male would be the T patch (most closely mimics natty T) applied before bed!

TS or TP solo injected daily let alone even when using low doses TC/TE as a base + TS or TP injected in the early am to take advantage of the peak would never mimc this.

As i have stated in previous threads.

Many fail to realize that T levels gradually rise overnight reaching peak in the early AM.


*elevated and near peak TT level during nighttime sleep, peak TT level around the time of morning awakening

*T production occurs in the greatest amount during sleep as recurring pulses at approximately 90 min intervals in healthy young males and approximately 140 min in healthy middle-aged males (91)








*The 24-hour pharmacokinetic profile of testosterone for patients on TNG treatment has two or three discrete peaks (“pulses”) of testosterone provoked by LH secretions that occur on average every 2 hours. A maximal peak of testosterone appears at about 1h (Tmax) followed by a return to endogenous, pre-dose levels, 4-6 hours later (t1/2 ~1h). The nadir (trough) between doses correlates well with pre-treatment endogenous levels at diagnosis.


*The unique, pulsatile, pharmacokinetic profile is believed to have limited impact on the HPG axis with significant trough time preserving luteinizing hormone (LH), follicle-stimulating hormone (FSH), endogenous testosterone production, and sperm counts, while also limiting excess RBC production, estradiol, DHT and PSA in clinical trials.

Post in thread 'Advice on low dose daily testosterone'

Jun 12, 2021

This is great. Would you think using testosterone suspension could be just a bit more than nasal and less than gel supression?

Regarding aqueous testosterone suspension, although there would be rapid absorption of the aqueous vehicle, the crystals of T depending on the particle size (human/veterinary grade) may very well behave like small implants which would be more slowly absorbed from the tissues although it is much faster acting than an esterified T such as (propionate).

With T base (oil/no ester) it would most likely be absorbed/degraded more quickly.




*Pulsatile...

• madman

• 

Thread 'Suppression of Serum LH and FSH in Adult Males following Exogenous Testosterone Suspension Administration (1972)'

Mar 1, 2025

* Samples of venous blood were obtained from 22 healthy adult males age 19-26 before and after the im injection of testosterone in aqueous suspension (Oreton©).


* The administration of the 12.5 and 25.0 mg of testosterone daily was reflected by markedly higher levels of serum testosterone. After the third dose of 25.0 mg, this level reached a peak within 16 hr after im administration and remained above control levels for at least 24 hr after the higher doses were administered. The rate of decline and the magnitude and duration of depression below...

• madman
• testosterone; gonadotropins; lh/fsh; hpta
• Replies: 2
• Forum: Testosterone and Men's Health Articles

• 

 

[Cataceous]

The doses of TS he is using are well below what anyone would use for sole TRT.

The nominal cumulative dose of 4.5 mg T daily is well over some estimates for total daily absorption with Natesto. Admittedly Natesto could be viewed as somewhat apart from TRT because of continued endogenous production—I sometimes facetiously call it TRT-Lite. There is also the issue discussed above as to whether my doses actually approach the nominal amounts. Nonetheless, this protocol could be characterized as "sole TRT" given that I have no evidence that my low but non-negligible LH is stimulating much production of endogenous testosterone.

I guess my point is that while these TS doses are low by injection standards, they are not so far from other modalities, such as transdermal formations. I suspect that the pharmacokinetic profile of TS gives it more bang for the buck, assuming that daily peak serum testosterone levels factor into the benefits we receive from testosterone.

Even then injecting once daily would never mimic the PK of nasal T gel which has been shown to have limited impact on suppression of the HPG-axis as T max is achieved within an hour which results in a very short-lived peak and levels return back to baseline 4-6 hrs later.

The data above are suggesting that if we could exclude the larger particles then TS would behave more like Natesto. Yes, three daily injections would be needed.

Do you have any thoughts on the pharmacokinetics of the water-based solution I described above? The subjective results have various interpretations—a pessimistic one being that the relatively high viscosity and tissue irritation from benzyl alcohol extend the half-life to that of TNE in oil or longer.

Daily injections of TS using doses that would allow one to achieve a high enough peak/trough would have a stronger impact on suppression HPG-axis.

This is borne out by my results. However, unlike with a TE/TP blend at perhaps similar dosing, TS allows some HPTA activity with gonadorelin alone. As noted above, the TE/TP blend required the stimulation of a SERM to achieve the same result.

Natty rise in endogenous T happens gradually overnight and highest levels are achieved in the early AM.

You could never mimic this with daily TS.

As with nasal gel, that's not really the intent. On the other hand, a TE/TP blend as rendered by AI isn't horrendous:

 

[Guided_by_Voices]

The possible interactions with non-target receptors, uncertain long-term safety and lack of endogenous origins for many of them. Anecdotally the SERM success stories are fairly rare, whereas it's common to see guys reporting good numbers but not great subjective results. Now this is in part a result of reporting bias, where happy guys are much less likely to be on the forums complaining about problems. However, if I'm remembering correctly, the FDA was initially loathe to clear enclomiphene for similar reasons.

Personally I have the sense that encomiphene was preventing me from getting the best results. It was still a significant improvement to regain some HPTA activity under TRT with the help of enclomiphene and gonadorelin, but now that I can contrast the experience with the gonadorelin/TS protocol, I feel it was lacking. It's not a completely neutral comparison, because as I've discussed here, the TS replacing the enanthate/propionate blend has unique pharmacokinetics that likely contribute to the results.

I feel like I've had a good experience with SERMs and while I'm not promoting them, I'll just make several observations:

- For most men, SERMs are probably either a fertility boost or a modality which will delay for a few years but not permanently avoid some form of full TRT. Hence, the really long-tem issues may not be an issue for people who are going to be on them for (as a maximum) less than 10 years.
- The most I've ever used is 50mg a week, which is a ramp-down daily dose for some PCT protocols. I think part of the issue is that as with MT2/PT-141, many people start with an excessive dose and then blame the compound
- For whatever reason, I seem to get better subjective results from Clomid vs. Enclomiphene so perhaps Zuclomiphene is actually doing something beneficial. It's long-half life further complicates things since it essentially changes Clomid into a different drug over time, but for a few months at a time the combination seems to work for me. I used to do a washout and reset when I was Clomid-only, but I understand some people would not be ok with that.

 

[Cataceous]

...
- For whatever reason, I seem to get better subjective results from Clomid vs. Enclomiphene so perhaps Zuclomiphene is actually doing something beneficial. ...

I have seen a few reports like this, where guys favor clomiphene over enclomiphene. The zuclomiphene isomer is essentially like estrogen—strong enough to knock out the HPTA when given alone—so one hypothesis is that these men have low-end estrogenic activity at the start and thus benefit from the boost given by zuclomiphene.

 

[Guided_by_Voices]

I have seen a few reports like this, where guys favor clomiphene over enclomiphene. The zuclomiphene isomer is essentially like estrogen—strong enough to knock out the HPTA when given alone—so one hypothesis is that these men have low-end estrogenic activity at the start and thus benefit from the boost given by zuclomiphene.

That theory fits my bloodwork

 

[Cataceous]

This thread is a reasonable place to expand a little on the hypothesis that short-term fluctuations in testosterone affect our subjective results. I'd asked the Grok AI about natural pulsatile delivery of testosterone. It was suggesting pretty significant short-lived swings in testosterone that are not seen in the usual diurnal testosterone graphs. I asked it to render one for me:

Proceeding with the caveat that I have not independently verified this characterization—contrast this graph with the simulation of three daily TS doses from earlier in this thread:

Does this better mimicry of pulsatile delivery drive the improved subjective results? For completeness, here is the TE/TP (testosterone enanthate / testosterone propionate) blend simulation:

This better captures the diurnal rhythm, but lacks the short-lived peaks of pulsatile delivery.

For me, adding gonadorelin to the TE/TP blend protocol was a significant improvement. But the switch to TS/gonadorelin took things to a new level.