Pharmacokinetic Profile of Testosterone Suspension: A Case Study

[Cataceous]

Lately I’ve been insinuating that some testosterone suspension products may qualify as fast-acting, and therefore be in the same league as testosterone nasal gels and buccal troches. The “fast-acting” quality is important if the goal is to retain HPTA function in the presence of exogenous testosterone. It was time to put my money where my mouth is in order to see what’s actually happening when I inject testosterone suspension.

The results are promising, but not as definitive as I’d hoped for due to some confounding factors.

Materials and Methods

The product used was Pharmacom testosterone suspension (TS), 100 mg/mL, diluted with bacteriostatic water to a nominal 50 mg/mL. It was believed that existing HPTA activity could result in a nontrivial baseline of endogenous testosterone. In an attempt to reduce that, two 250 mcg doses of ganirelix were procured and injected subcutaneously at 10 hours and 3 hours prior to the subcutaneous injection of a dose of 3 mg—6 units—of the TS. Ganirelix is a GnRH antagonist more commonly used in women. Ganirelix seemed appropriate here because its 13 hour elimination half-life would not lead to prolonged HPTA suppression.

Baseline serum total testosterone was measured by Labcorp ECLIA just prior to the TS injection, along with albumin and SHBG. Serum total testosterone was subsequently measured at 0.5, 1, 2 and 4 hours post-injection.

Results

Baseline SHBG was 40.5 nMol/L. Albumin was 4.1 g/dL. Baseline serum testosterone was 270 ng/dL (!). Changes from baseline testosterone are as follows:

Discussion

The fast post-injection rise in serum testosterone and Tmax of 30 minutes are promising with respect to the premise of fast action, as is the relatively large drop from the one-hour level to the two-hour level. The latter yields a half-life of about 1.7 hours, in line with the manufacturer’s claim of two hours. However, the four-hour blood level is confounding, suggesting a much longer half-life if taken verbatim.

The relatively high baseline testosterone of 270 ng/dL was unexpected. The hope had been to drive it below 50 ng/dL. The reason for the high level is unclear. Two possibilities: the ganirelix was ineffective for some reason; or there was a nontrivial residual from the previous injection of a nominal 1.5 mg TS, which took place about 16 hours prior to the study injection. Either case is problematic with respect to the TS half-life. If the ganirelix was ineffective then endogenous production during the study could interfere with determining the half-life. If there was a significant carryover from the previous injection then the implication is a much longer half-life than expected. There could be a combination of the two factors, or something else entirely.

The area under the curve is troublingly small, possibly 20-fold lower than expected. This is difficult to explain, and the magnitude of the discrepancy makes the obvious explanations seem very unlikely. These include under-dosing of the product, improper dilution, and injection-site leakage. Another explanation with marginal plausibility is that the 31 gauge needle acts as a filter, excluding larger particles and greatly reducing the effective concentration.

Acknowledgements

Thanks to Defy Medical for their willingness to prescribe ganirelix. Thanks to the staff at my local Labcorp location for their cooperation and assistance.

 

[FunkOdyssey]

I love that you did this experiment and wrote up all of the details for us. Very puzzling results though!

 

[Willyt]

Thanks Cat for the attempt to isolate the effects of Suspension. What are your next steps?

Would be interesting to see the TT/FT/HPTA blood results when available

I continue to dabble with TNE oil-base which subjectively speaking seems to stick around longer than water-based Suspension

 

[Cataceous]

... What are your next steps?
...

I've taken the first one, which is to investigate where the missing testosterone went. It appears likely that the filtering action of a small needle is part of the problem, along with wastage via particle deposition on the vials. The empty vial that had contained 1 mL of the TS and 1 mL of bacteriostatic water had noticeable residue after all of the fluid was eventually removed and injected. I dissolved this residue in 2 mL of ethanol and heated it in an open container to 120° C (~250° F) for about 20 minutes. I did the same with a control sample of 2 mL ethanol, to account for impurities in the alcohol. With the ethanol evaporated the weight of the control residue was at most 10 mg. The weight of the TS residue was 160 mg (!). The fact that the weight of this residue is more than the nominal initial testosterone content of 100 mg is a new puzzle. Typical TS excipients (sodium phosphate dibasic, polysorbate 80, sodium chloride) are highly water soluble and thus should not remain in significant quantity when the bulk of the liquid has been removed. In any case, this result suggests that a lot of the testosterone was not withdrawn by the 31 gauge needle. I also noted a lot of residue in the stock TS 10 mL vial, even after evacuation with a large bore needle. Using the same technique as above I found this residue to weigh 220 mg. It seems suspect that a single 1 mL withdrawal and the stock vial residue would together contain more than a third of the nominal total testosterone in the vial. But I don't have another explanation unless there is some other excipient that is precipitating in situ.

If this explanation for the lack of testosterone is correct then it could have an effect on the measured pharmacokinetics. If only the smallest 5-10% of particles are being used then we might expect this to result in faster absorption and a smaller apparent half-life. It's also a remarkably inefficient way to use TS. In hindsight it would have been more useful to the TRT community if I had used a larger-bore needle along with the stock TS product. I'm not ready to do this now, as I'm heading in a slightly different direction. Perhaps a Defy patient would volunteer, as then it's a relatively inexpensive experiment—$100 for the five testosterone tests.

Where I'm headed with this is to try adding different solvents to the TS with the hope of attaining smaller particles overall via some dissolving, which in turn should allow continued use of 31 gauge needles and the desired fast action, along with less waste. I'm starting a trial in which the 1 mL of bacteriostatic water is replaced with 0.8 mL of polyethylene glycol 400 and 0.2 mL of benzyl alcohol. Visually the result is better, with the individual testosterone particles appearing less prominent and less prone to deposition on the vial sides. However, only time will tell if this is a useful formula.

A further drawback of the ostensible micro-dosing with TS is that it calls into question claims about HPTA function. That is, if I'm only taking on the order of 1 mg per day of testosterone then I can't tell whether HPTA activation is due to the fast-acting nature of the testosterone or to the low dose itself. On the other hand, it's a remarkable finding that dropping to such a low dose of testosterone can lead to consistently good results in potential problem areas: libido↑, sexual function↑; even non-problem areas: lipids↑; at the expense of athleticism↓, maybe body composition↓→.

 

[Guided_by_Voices]

it's a remarkable finding that dropping to such a low dose of testosterone can lead to consistently good results in potential problem areas: libido↑, sexual function↑; even non-problem areas: lipids↑; at the expense of athleticism↓, maybe body composition↓→.

FWIW, I've found the same thing when I cut my dose of Test cyp, at least in the short term. I would do so permanently and add in Oxandrolone for the anabolic effects, except that my E2 is already very low and I haven't wanted to get into supplementing E2 directly.

 

[Forty2]

FWIW, I've found the same thing when I cut my dose of Test cyp, at least in the short term. I would do so permanently and add in Oxandrolone for the anabolic effects, except that my E2 is already very low and I haven't wanted to get into supplementing E2 directly.

Have you tried hCG with low dose Oxandrolone on hard workout days?

 

[Guided_by_Voices]

Have you tried hCG with low dose Oxandrolone on hard workout days?

Yes. It's not going to do as much as that plus other anabolics, however I think it's a viable approach if one want a moderate boost. Many people who start TRT looking primarily for gym gains should IMO start with some sort of minimally suppressive protocol such as enclomiphene/oxandrolone, hcg/oxandrolone, and/or some form of HGH sectretagouge or HGH. This seems to me to be much lower risk that full TRT if one's goal is a bit better strength and body composition. A lot would depend on where someone is starting from however. There was a study that showed only 40% suppression of T IIRC over a 12 week period with Oxandrolone that used what IMO was an excessive and unnecessary dose. Someone (male) who is already close to their potential should see a meaningful boost from 10mg 4 times per week IME.

I think something similar would also make sense for the Oral T crowd. The concept that Maximus has been promoting like they invented it has been around at least since before 2010, but has never really caught on since many people will only consider extreme options. and the less suppressive forms of T (excluding TNE) have only come on the scene fairly recently.

 

[Forty2]

Yes. It's not going to do as much as that plus other anabolics, however I think it's a viable approach if one want a moderate boost. Many people who start TRT looking primarily for gym gains should IMO start with some sort of minimally suppressive protocol such as enclomiphene/oxandrolone, hcg/oxandrolone, and/or some form of HGH sectretagouge or HGH. This seems to me to be much lower risk that full TRT if one's goal is a bit better strength and body composition. A lot would depend on where someone is starting from however. There was a study that showed only 40% suppression of T IIRC over a 12 week period with Oxandrolone that used what IMO was an excessive and unnecessary dose. Someone (male) who is already close to their potential should see a meaningful boost from 10mg 4 times per week IME.

I think something similar would also make sense for the Oral T crowd. The concept that Maximus has been promoting like they invented it has been around at least since before 2010, but has never really caught on since many people will only consider extreme options. and the less suppressive forms of T (excluding TNE) have only come on the scene fairly recently.

I was thinking more along the lines of 5mg Oxandrolone every 3 days for a guy on hCG monotherapy to aid in anabolism. Such a protocol is unlikely to adversely affect lipids and interfere the testosterone boosting effects from hCG. The question is, will a dose that low be enough to aid recovery from a heavy lifting workout every 3 days?

 

[Guided_by_Voices]

I was thinking more along the lines of 5mg Oxandrolone every 3 days for a guy on hCG monotherapy to aid in anabolism. Such a protocol is unlikely to adversely affect lipids and interfere the testosterone boosting effects from hCG. The question is, will a dose that low be enough to aid recovery from a heavy lifting workout every 3 days?

I would try it and see. A lot will depend on your how recovery-friendly your lifting protocol is. I (almost) never do a set to failure, but I do a lot of near-maximal sets and I have found that this massively reduces the recovery time needed while also letting me do far more near-maximal volume on more movements. It also depends on whether you're hitting the same movement every three days or just doing a hard workout with different movements every three days. I'm assuming you mean you would do 5mg pre-workout every three days. Other things like your weight and protein intake will play a role, but I would expect you would notice a small benefit.

 

[Forty2]

I would try it and see. A lot will depend on your how recovery-friendly your lifting protocol is. I (almost) never do a set to failure, but I do a lot of near-maximal sets and I have found that this massively reduces the recovery time needed while also letting me do far more near-maximal volume on more movements. It also depends on whether you're hitting the same movement every three days or just doing a hard workout with different movements every three days. I'm assuming you mean you would do 5mg pre-workout every three days. Other things like your weight and protein intake will play a role, but I would expect you would notice a small benefit.

I also don't take any sets to failure and never do more than 2 sets of heavy compound exercises per workout. I do a heavy upper body gym session every 6 days and a heavy lower body session every 6 days (3 days after my upper body workout). I take a deload week every 3 weeks, yet still experience a lot of muscle soreness in the days following my heavy lifting. I'm hoping that the addition of low dose oxandrolone will help to reduce this soreness.

 

[Guided_by_Voices]

I also don't take any sets to failure and never do more than 2 sets of heavy compound exercises per workout. I do a heavy upper body gym session every 6 days and a heavy lower body session every 6 days (3 days after my upper body workout). I take a deload week every 3 weeks, yet still experience a lot of muscle soreness in the days following my heavy lifting. I'm hoping that the addition of low dose oxandrolone will help to reduce this soreness.

If soreness is your primary issue, it’s possible that lack of anabolism is part of the problem, but it sounds like your protocol should be doable without much soreness. Jumping to Oxandrolone before ruling out some other fundamental issues seems a bit premature so before you jump to that I would consider:

Stretching – I hate stretching as much as the next guy, but I have found it is essential to minimize soreness. Stretching on your off days and before/after your lifting is critical. It doesn’t have to be extreme, just enough to eliminate tightness in the muscles.

Warm-ups – Jumping to your top weights too quickly can cause soreness, or worse. Err on the side of more warm-up sets and make them as productive as you can by, for example, alternating wide and close grip on your bench warm-ups.

Protein – Collagen and glycine are magic potions IME. Consider supplementing with these, and also err on the side of a lot of high-quality protein in the 24 hours after each of your lifting sessions. Creatine supplementation is also worth a try.

Blood flow – I have found soreness resolves more quickly if you have consistent blow flow through the muscles. Try adding a “light day” so that after your heavy leg work you do light upper body and vice versa. This should add no more than 15 minutes and use fairly light weights but should stimulate blood flow through the muscles. Also consider an easy 20-30 minute bike ride the day after each session which will also stimulate blood flow.

Aspirin – Consider taking a full-strength aspirin pre-workout if your body is over-doing inflammation, this may help resolve it and it has other benefits as well. And no, it will not slow your strength progress.

If you still have soreness issues after doing those things, then add in the Oxandrolone. I would divide it in two doses taken pre-workout so that it is most active during the post-workout adaptation window but you can experiment and see what works best for you. Personally, I only get sore when I do something I haven’t done for several weeks but it sounds like you are on a good frequency. I would not think a de-load is necessary as often as you are doing so unless your body tells you you need one.

 

[Willyt]

The weight of the TS residue was 160 mg (!). The fact that the weight of this residue is more than the nominal initial testosterone content of 100 mg is a new puzzle.

Fascinating! I wondered whether this possible. You are truly a mad scientist.

On a related point, why don't pharma companies use smaller crystals for Suspension? If they could, would it help dissolve the testosterone in water? Or is that why there is TNE oil-base as alternative?

I would imagine the that traditional bodybuilder type using TS probably uses much larger gauge needle since they are used to that for IM and are injecting much, much larger doses.

 

[Cataceous]

...
On a related point, why don't pharma companies use smaller crystals for Suspension? If they could, would it help dissolve the testosterone in water? Or is that why there is TNE oil-base as alternative?
...

I don't know the practical limitations on particle size for testosterone suspension. Maybe there's a cost-benefit tradeoff? In addition, the interest in very fast-acting testosterone is more recent and still limited.

Bear in mind that testosterone basically does not dissolve in water. However, if you add enough of other solvents then you can attain a water-based solution, which is what I'm working on. The formula I mentioned above is partway there. Dissolving all of the particles probably requires a greater proportion of alcohol, benzyl and/or ethyl. The problem is that using higher concentrations can be irritating or even damaging to tissue. I will see what's possible.