Subcutaneous Administration of Testosterone

[JSayaMD]

Yes water does not dissolve fat, water separates from fat. Oil also does not dissolve fat either, however, but disperses and "blends" in fat.

Careful or some may think they can inject oil into their adipose tissue to dissolve it (an oil injectable lipo per se)...lol.

To more closely mimic the natural hormone patterns (peak AM, nadir PM), you would agree nothing beats daily transdermals, but there is the issue of relatively more E and DHT with that route as well (although significant for some and not for others).

Anecdotal reports for the subq injections seem to very greatly (as with most hormonal issues), as I often tell patients "there is NO perfect method of HRT/TRT...if there was, everyone would be using THAT method." Pt preference carries a lot of weight for me, as long as they are informed on the pros/cons.

Dr Saya

 

[Nelson Vergel]

I guess we will soon see data on subcutaneous T injections

Antares Pharma, Inc. announced that the first patients have been dosed in a clinical study evaluating testosterone enanthate administered weekly by subcutaneous injection at doses of 50 mg and 100 mg via the VIBEX™ QuickShot™ auto injector device in testosterone deficient adult males. Up to 45 patients will be enrolled at approximately eight investigative sites in the United States. http://www.businesswire.com/news/ho...res-Pharma-Announces-Patients-Dosed-VIBEX™-QS

 

[JSayaMD]

Interesting, although I'm sure Dr Crisler would take issue (as would I) with the WEEKLY Subq injections.

It's a start though...

Dr Saya

 

[robs2nd75]

There must be more to this, as the test cyp has to be going somewhere.

The only thing I can add, which may have no significance, is I have dark and foul smelling urine w/in hours of SC injection.

 

[Keith Willse]

Dr Eugene Shippen started the whole Subq injection route for testosterone. It's a shame there is no study data on this but I'll bet his notes are worth more than any study.

 

[Dr. John Crisler]

I guess we will soon see data on subcutaneous T injections

Antares Pharma, Inc. announced that the first patients have been dosed in a clinical study evaluating testosterone enanthate administered weekly by subcutaneous injection at doses of 50 mg and 100 mg via the VIBEX™ QuickShot™ auto injector device in testosterone deficient adult males. Up to 45 patients will be enrolled at approximately eight investigative sites in the United States. http://www.businesswire.com/news/ho...res-Pharma-Announces-Patients-Dosed-VIBEX™-QS

Well, something ELSE I would not have known without your blog(s).

I inserted the other three studies I found here on SC injecting into the lecture I will delivering before the Age Management Medicine Group on Halloween.

 

[Dr. John Crisler]

Dr Eugene Shippen started the whole Subq injection route for testosterone. It's a shame there is no study data on this but I'll bet his notes are worth more than any study.

For sure.

I walked into an A4M medical conference one time while Dr. Shippen was on stage (no disrespect at showing up late--I was unavoidably detained by my Co-Hosting resonsibilities) some years ago. He was talking about SC injecting.

He said, upon seeing me coming down the aisle, "why Dr. Crisler doesn't get with it is beyond me".

I'll call him, and see what new things he has to say about the subject.

 

[Dr. John Crisler]

Interesting, although I'm sure Dr Crisler would take issue (as would I) with the WEEKLY Subq injections.

It's a start though...

Dr Saya

Moving the injection site to the fat pads above the glutes--where I do my own now--means larger (weekly) injections are now preferable via SC technique as well.

 

[JSayaMD]

Moving the injection site to the fat pads above the glutes--where I do my own now--means larger (weekly) injections are now preferable via SC technique as well.

I am now confused...

And variability is part and parcel of youth. As we age, even though the peaks and nadirs may stay the same, frequency declines....and so then does hormonal output. Smaller, more frequent injections produce a saw tooth pattern which really seems to work well for them.

Seems conflicting, which do you prefer?

Dr Saya

 

[Dr. John Crisler]

I am now confused...



Seems conflicting, which do you prefer?

Dr Saya

If the guys has a higher SHBG, he must use a larger, less frequent injection. He has to be able to mass action over the top of all that SHBG.

You can get up 3/4mL into the fat pads above the glutes with no problem. No more IM for my guys (unless they insist, of course, because they feel IM works better for them).

But for those with lower SHBG, to keep them from hyperexcreting so much T into their urine (wasteful), smaller, more frequent shots are more often the answer.

These are all but tools in the Interventional Endocrinologist's doctor's tool bag. And, as you have pointed out, there is so much variability across the population, there are no hard and fast rules.

 

[JSayaMD]

I get the idea of "mass action" over the top of all of the SHBG, but still have difficulty reconciling this with larger, less frequent injections based solely on SHBG levels. The pharmacodynamics of the injection (regardless of method... IM vs SubQ) should not be dramatically altered for that same injection technique based solely on the frequency of the injections. This is hard to grasp conceptually, but my pharmacology mentor hammered this in my head at UNC. Since pharmacodynamics (peak timing, nadir timing, half-life, etc) would NOT be altered by changing frequency of injection alone, would it not make more sense...to "mass action" over the SHBG for those with high SHBG levels... to simply do slightly higher dosing with each injection but keep the more frequent injection pattern as you stated to preserve the "sawtooth" physiology (which would basically be sacrificed, necessarily due to the pharmacodynamics of the ester, with the once weekly injections)?

Granted, there is no right answer, just boils down to smart people who understand the physiology involved coming up with their best approach based on the processes involved...

Dr Saya

 

[Dr. John Crisler]

I get the idea of "mass action" over the top of all of the SHBG, but still have difficulty reconciling this with larger, less frequent injections based solely on SHBG levels. The pharmacodynamics of the injection (regardless of method... IM vs SubQ) should not be dramatically altered for that same injection technique based solely on the frequency of the injections. This is hard to grasp conceptually, but my pharmacology mentor hammered this in my head at UNC. Since pharmacodynamics (peak timing, nadir timing, half-life, etc) would NOT be altered by changing frequency of injection alone, would it not make more sense...to "mass action" over the SHBG for those with high SHBG levels... to simply do slightly higher dosing with each injection but keep the more frequent injection pattern as you stated to preserve the "sawtooth" physiology (which would basically be sacrificed, necessarily due to the pharmacodynamics of the ester, with the once weekly injections)?

Granted, there is no right answer, just boils down to smart people who understand the physiology involved coming up with their best approach based on the processes involved...

Dr Saya

What your instructor is not taking into account is the fact this is not a closed system. That is why 50mg twice per week (all within 7 days) is not the same as 100mg every seven days.

When serum androgen levels rapidly rise, things change. Aromatase activity, for instance, accelerates. So you get more...and MORE....estrogen.

The excretion of testosterone via the kidneys also increases. It's like the body is trying to even things out. I know this because I have looked at thousands of 24 hour urinary labs (AND discussed my findings with Dr. Frank Nordt LOL).

With SHBG low, what appears in the bloodstream, from a given dose, is much more Free/Bioavailable T. More of this excess is excreted from the kidneys into the urine. It is, essentially, lost.

THIS is why (and one of the studies on SC injection posted on the old blog shows this), for instance, 40mg of test cyp injected twice per week is roughly equal to 100mg once per week. This I already knew from practical clinical experience. How nice when it is verified by a study later.

Basically, with low SHBG, the peak of an otherwise normal (closed system) serum androgen profile is clipped off, and down the toilet. And since we are giving another shot a few days later, so is the nadir (low point).

So, for the patient, they have more usable testosterone all during the week, and in a saw tooth pattern that favors the entropy which is part and parcel of youth.

Conversely, with a higher SHBG you just never attain serum levels sufficient to get over the top of it, and establish good Free/Bio levels.

 

[Dr. John Crisler]

What your instructor is not taking into account is the fact this is not a closed system. That is why 50mg twice per week (all within 7 days) is not the same as 100mg every seven days.

When serum androgen levels rapidly rise, things change. Aromatase activity, for instance, accelerates. So you get more...and MORE....estrogen.

The excretion of testosterone via the kidneys also increases. It's like the body is trying to even things out. I know this because I have looked at thousands of 24 hour urinary labs (AND discussed my findings with Dr. Frank Nordt LOL).

With SHBG low, what appears in the bloodstream, from a given dose, is much more Free/Bioavailable T. More of this excess is excreted from the kidneys into the urine. It is, essentially, lost.

THIS is why (and one of the studies on SC injection posted on the old blog shows this), for instance, 40mg of test cyp injected twice per week is roughly equal to 100mg once per week. This I already knew from practical clinical experience. How nice when it is verified by a study later.

Basically, with low SHBG, the peak of an otherwise normal (closed system) serum androgen profile is clipped off, and down the toilet. And since we are giving another shot a few days later, so is the nadir (low point).

So, for the patient, they have more usable testosterone all during the week, and in a saw tooth pattern that favors the entropy which is part and parcel of youth.

Conversely, with a higher SHBG you just never attain serum levels sufficient to get over the top of it, and establish good Free/Bio levels.

This is why 24 hour (not spot!) urines are the way to go for TD's.

Also why I want my guys to wait until the second half of their injection week to collect their urine sample; things are kinda weird until then.

This is also why I always get a Total T and a SHBG to go along with a 24 hour urine. IF SHBG is lower, T (actually, Free T) on the urine panel will be comparatively high to serum Total T. It helps me set the range. With 24 hour urines, it is more the shape of the profile than the actual numbers. Found two pituitary tumors like this: the shape of the profile was just weird.

 

[JSayaMD]

But with ONCE WEEKLY injections (especially SubQ), you would likely have much LESS sawtooth effect than with multiple more frequent injections. I fail to see how a once weekly injection would produce more sawtooth effect than smaller more frequent injections... there is no physiologic or pharmacodynamic explanation for that, regardless of an open or closed system. It cannot happen.

Larger once weekly injections would produce a more broad sloping "sawtooth" pattern like a very dull saw, while more frequent injections would produce more frequent "points" on that saw blade...this is all assuming that the sawtooth pattern is indeed ideal, which some would debate as well but I agree VARIATION (sawtooth if you want to call it that) is good, how much variation or the extent of that variation (hourly variation, daily variation, weekly variation, etc) that is optimal is another question, although hourly variation most closely approximates the biological system but is unfortunately only approximated treatment-wise by topicals... let's create the perfect TRT modality/route, dominate the TRT field, and then buy an island to rename "The Man Island- but Women Welcome!"...lol

Dr Saya

Dr Saya

 

[Dr. John Crisler]

Part of the reason for the "Crisler Method" of using HCG on days 6 and 7 of the injection week is to saw tooth the serum androgen level; among other things.

 

[Dr. John Crisler]

But with ONCE WEEKLY injections (especially SubQ), you would likely have much LESS sawtooth effect than with multiple more frequent injections. I fail to see how a once weekly injection would produce more sawtooth effect than smaller more frequent injections... there is no physiologic or pharmacodynamic explanation for that, regardless of an open or closed system. It cannot happen.

Larger once weekly injections would produce a more broad sloping "sawtooth" pattern like a very dull saw, while more frequent injections would produce more frequent "points" on that saw blade...this is all assuming that the sawtooth pattern is indeed ideal, which some would debate as well but I agree VARIATION (sawtooth if you want to call it that) is good, how much variation or the extent of that variation (hourly variation, daily variation, weekly variation, etc) that is optimal is another question, although hourly variation most closely approximates the biological system but is unfortunately only approximated treatment-wise by topicals... let's create the perfect TRT modality/route, dominate the TRT field, and then buy an island to rename "The Man Island- but Women Welcome!"...lol

Dr Saya

Dr Saya

The multiple injections produces the saw tooth. Did I write that wrong some where?

Girls always have wanted to get into the boyz clubhouse. We welcome that. LOL

 

[JSayaMD]

IF... "sawtooth" is the goal, agree with low SHBG a smaller more frequent injection is ideal.

IF... "sawtooth" is the goal, disagree that with a high SHBG a ONCE weekly larger injection would be better...IF sawtooth pattern is the goal...then sticking with the more frequent injections (same pharmacodynamics = same sawtooth pattern), but just slightly HIGHER dosing with each injection to overcome or "mass action" over the SHBG would seem preferred. Keeps same sawtooth pattern as with lower SHBG (due to not changing injection frequency), but overcomes SHBG to produce adequate free T levels. You can have your cake (keep same sawtooth pattern) and eat it too (overcome the high SHBG to optimize free T)!

Dr Saya

 

[SuperDutyDave]

Have to say this is an extremely educational discussion......dealing with this first hand it's great to hear the science of why things are prescribed and what is the theory is for why they work.

Thank you Dr. John

Thank you Dr. Saya

 

[Nelson Vergel]

I have enjoyed the above discussion tremendously.

However, I have to caution that unless there is a reference I have missed, there are absolutely no pharmacokinetics studies published that show Cmax, Cmin and AUC for 50-100 mg twice weekly injections of any testosterone ester via IM or subcutaneous route. If anyone has seen any references, please post.

 

[Nelson Vergel]

IM injections of 100-200 weekly work well in many men. Do not let others make you feel like you have to inject more than once a week. Most men are too busy to inject frequently.

This whole argument will end when testosterone undecanoate gets approved in the United States.