SUBQ vs IM physiology

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Dwhit

New Member
Having found that I have a lowish SHBG (22; normal range 16.5-55.9), and having what I believe to be related clincal symptoms, I've decided to follow the advice of some members of this forum, and increase the frequency of my injections from 2x/wk to daily injections. What I'm now trying to decide is whether I should go with shallow IM vs. SC. I'd prefer SC, but it seems like some guys (not all) have issues with SC resulting in lower T levels and higher estrogen levels. (The estrogen issue is very important to me as I am prone to gynecomastia, and I'd like to avoid an AI if possible.)

I've also been scouring the literature for guidance. I came across a study (Sex Med 201;3:269-279) in which one group of patients was given 100mg testosterone enanthate subq 1x/week, and another group was given 200mg testosterone enanthate IM 1x/week. At steady state, the subq group had a mean T of 896 ng/dL, while the IM group had a mean T of 1659 ng/dL. This is not surprising, given that the IM group was getting twice as much T. The interesting thing, however, is what happened to their estrogen levels. Despite the greatly different T levels, both groups had the same mean E2 level of about 50 pg/mL. In other words, the IM group had a T:E ratio almost double the SC group! Now granted, they were doing weekly injections not daily, but clearly there was some extra conversion to estrogen with the subq group. I assumed this was due to aromatase in the subq tissues.

But the explanation is not that simple. As pointed out by Dr. Saya in another thread, we are not injecting testosterone, but rather we are injecting T esters, and T esters should not be affected by aromatase. Now, I suppose if you inject a big blob of oil (as with weekly SC injections), there might be some local conversion of the esterified T into active T, and then subsequent conversion into estrogen. However, with smaller blobs of oil (as with daily SC injections) I imagined systemic absorption should be rapid enough that there is insufficient time for any local conversion--the esterified T should safely make it into the systemic circulation, where aromatase becomes less of an issue. This line of reasoning would explain both the study I mentioned above, where they used big weekly injections, as well as the experience of some on this forum, where small daily injections made no difference.

Well, anyway, that was my thinking. However, as I continued to look into the research, I realized the picture in my mind was incorrect, or at least incomplete. What I had originally pictured in my mind is that the blob of oil we inject into our bodies, whether IM or SC, is absorbed systemically fairly rapidly. I pictured microscopic droplets of oil being distributed thoughout the body in a matter of minutes or hours. I then imagined the esterified T within these tiny droplets being very gradually converted into active form (by the esterase enzyme--which is ubiquitous in the body). This conversion takes place over a matter of days, leading to the long half lives of T esters (e.g. 8 days for testosterone cypionate).

So this is how I pictured things happening. But I was wrong. This is not what happens. As I said earlier, esterase is everywhere in the body. This means that as soon as esterified testosterone gets absorbed into the circulation, it is almost immediately converted to active testosterone. From one pharmacology textbook: "after intravenous injection of testosterone enanthate or testosterone, these compounds have parallel pharmacokinetics (Sokol and Swerdloff 1986)." So, in other words, if you inject testosterone enanthate intravenously (I don't recommend this!) it will have the same half life as pure testosterone (4-24 hours). In order to have a prolonged half life of several days, there must be a local depot effect. The blob of oil must remain in place at the injection site (or at least the associated esterified testosterone must remain in place) for many days.

Based upon this line of reasoning, I remain concerned about SC injections. I think the oil stays in place for a very long time. I'm curious if anyone has gotten labs and compared estrogen levels between daily IM and daily SC.

The bottom line, of course, is to get my own baseline and follow-up labs, which is exactly what I plan on doing. But in the meantime I find it interesting to think about such things. I also found some interesting information regarding different levels of aromatase activity in different fatty tissues (thigh and buttock area has much greater activity than abdomen and chest). There is also some interesting research regarding how the viscosity of the oil affects absorbtion--even the preserving agent has an effect on viscosity and absorption. Perhaps one or more of these variables might explain the different experiences on this forum.

Any thoughts? Feel free to criticize my thought process!
 
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maxadvance

Active Member
Wow, just wow. Paralysis by analysis of your own version of broscience. How about just seeing a Doctor who's already seen thousands of patients and has seen results of patients with daily subq injections instead.
 

ERO

Member
Most guys do not notice any difference, but a lot of us prefer insulin syringes in the shoulder area, which for most is a shallow IM.
 

CoastWatcher

Moderator
I have injected on a daily basis for over two years. For a three month period,mineralized I was injecting SubQ. I tested my levels. I then injected on a shallow IM basis for slightly over three months. My estradiol varied by .3 of a point.

I stick a needle into some portion of my anatomy and push the plunger. My doctor told me she's never had a patient report significant differences with one method as opposed to the other.
 

madman

Super Moderator
Having found that I have a lowish SHBG (22; normal range 16.5-55.9), and having what I believe to be related clincal symptoms, I've decided to follow the advice of some members of this forum, and increase the frequency of my injections from 2x/wk to daily injections. What I'm now trying to decide is whether I should go with shallow IM vs. SC. I'd prefer SC, but it seems like some guys (not all) have issues with SC resulting in lower T levels and higher estrogen levels. (The estrogen issue is very important to me as I am prone to gynecomastia, and I'd like to avoid an AI if possible.)

I've also been scouring the literature for guidance. I came across a study (Sex Med 201;3:269-279) in which one group of patients was given 100mg testosterone enanthate subq 1x/week, and another group was given 200mg testosterone enanthate IM 1x/week. At steady state, the subq group had a mean T of 896 ng/dL, while the IM group had a mean T of 1659 ng/dL. This is not surprising, given that the IM group was getting twice as much T. The interesting thing, however, is what happened to their estrogen levels. Despite the greatly different T levels, both groups had the same mean E2 level of about 50 pg/mL. In other words, the IM group had a T:E ratio almost double the SC group! Now granted, they were doing weekly injections not daily, but clearly there was some extra conversion to estrogen with the subq group. I assumed this was due to aromatase in the subq tissues.

But the explanation is not that simple. As pointed out by Dr. Saya in another thread, we are not injecting testosterone, but rather we are injecting T esters, and T esters should not be affected by aromatase. Now, I suppose if you inject a big blob of oil (as with weekly SC injections), there might be some local conversion of the esterified T into active T, and then subsequent conversion into estrogen. However, with smaller blobs of oil (as with daily SC injections) I imagined systemic absorption should be rapid enough that there is insufficient time for any local conversion--the esterified T should safely make it into the systemic circulation, where aromatase becomes less of an issue. This line of reasoning would explain both the study I mentioned above, where they used big weekly injections, as well as the experience of some on this forum, where small daily injections made no difference.

Well, anyway, that was my thinking. However, as I continued to look into the research, I realized the picture in my mind was incorrect, or at least incomplete. What I had originally pictured in my mind is that the blob of oil we inject into our bodies, whether IM or SC, is absorbed systemically fairly rapidly. I pictured microscopic droplets of oil being distributed thoughout the body in a matter of minutes or hours. I then imagined the esterified T within these tiny droplets being very gradually converted into active form (by the esterase enzyme--which is ubiquitous in the body). This conversion takes place over a matter of days, leading to the long half lives of T esters (e.g. 8 days for testosterone cypionate).

So this is how I pictured things happening. But I was wrong. This is not what happens. As I said earlier, esterase is everywhere in the body. This means that as soon as esterified testosterone gets absorbed into the circulation, it is almost immediately converted to active testosterone. From one pharmacology textbook: "after intravenous injection of testosterone enanthate or testosterone, these compounds have parallel pharmacokinetics (Sokol and Swerdloff 1986)." So, in other words, if you inject testosterone enanthate intravenously (I don't recommend this!) it will have the same half life as pure testosterone (4-24 hours). In order to have a prolonged half life of several days, there must be a local depot effect. The blob of oil must remain in place at the injection site (or at least the associated esterified testosterone must remain in place) for many days.

Based upon this line of reasoning, I remain concerned about SC injections. I think the oil stays in place for a very long time. I'm curious if anyone has gotten labs and compared estrogen levels between daily IM and daily SC.

The bottom line, of course, is to get my own baseline and follow-up labs, which is exactly what I plan on doing. But in the meantime I find it interesting to think about such things. I also found some interesting information regarding different levels of aromatase activity in different fatty tissues (thigh and buttock area has much greater activity than abdomen and chest). There is also some interesting research regarding how the viscosity of the oil affects absorbtion--even the preserving agent has an effect on viscosity and absorption. Perhaps one or more of these variables might explain the different experiences on this forum.

Any thoughts? Feel free to criticize my thought process!

You are overthinking this too much. There will be no difference in absorption rates between im vs sub-q, some may claim one is better than the other but it does not matter. As far as e2 conversion testosterone dosage/excess adipose tissue and most of all genetics are key factors. As some using low testosterone doses and even lean individuals can struggle with e2 related issues.
 

CoastWatcher

Moderator
You are overthinking this too much. There will be no difference in absorption rates between im vs sub-q, some may claim one is better than the other but it does not matter. As far as e2 conversion testosterone dosage/excess adipose tissue and most of all genetics are key factors. As some using low testosterone doses and even lean individuals can struggle with e2 related issues.

Very well put.
 

Dwhit

New Member
I have injected on a daily basis for over two years. For a three month period,mineralized I was injecting SubQ. I tested my levels. I then injected on a shallow IM basis for slightly over three months. My estradiol varied by .3 of a point.

I stick a needle into some portion of my anatomy and push the plunger. My doctor told me she's never had a patient report significant differences with one method as opposed to the other.

Thanks! Were you using an AI at the time?
 

Dwhit

New Member
You are overthinking this too much. There will be no difference in absorption rates between im vs sub-q, some may claim one is better than the other but it does not matter. As far as e2 conversion testosterone dosage/excess adipose tissue and most of all genetics are key factors. As some using low testosterone doses and even lean individuals can struggle with e2 related issues.

Yeah, I like to think about these things having a physiology background myself. Sorry if it was overkill. I'm not sitting in a room pulling my hair out over what to do next for myself. I realize that the bottom line is that every protocol has its trade offs, and every individual is different, and at the end of the day you go with what works. But maybe by delving into the underlying physiology, we can better optimize protocols, and better help guys with E2 issues or DHT issues or SHBG issues.
 
You raise some interesting points with your logic and the studies you provided, however, I think the consensus between most of the top trt doctors is that it really makes no difference. I know for a fact that Dr Crisler prefers subq, but many others prefer IM. Personally, I think subQ is significantly more painful than IM (using an insulin needle either way). If you're really curious, you could try 6 weeks IM, get blood work, followed by 6 weeks subQ, get blood work, and determine for yourself if there is any palpable difference.
 

Guided_by_Voices

Well-Known Member
When I was on HCG mono I looked into this for HCG and I remember finding studies, and my doctor at the time said, that that there is definitely a difference for HCG. IM produces a higher peak and faster decline and SubQ produces a lower but longer wave. That is why the insert with some HCG compounds will say to inject IM. I think the answer as with so many things, is that we don't know exctly what is going on in the body and there is no substitute for trying them both and seeing if you can tell a difference. Many people get annoying lumps in their abdomen fat from SubQ and I am one of those people. I have been doing IM for a while but I haven't been able to tell a huge difference in how I feel overall between the two.
 

Dwhit

New Member
You raise some interesting points with your logic and the studies you provided, however, I think the consensus between most of the top trt doctors is that it really makes no difference. I know for a fact that Dr Crisler prefers subq, but many others prefer IM. Personally, I think subQ is significantly more painful than IM (using an insulin needle either way). If you're really curious, you could try 6 weeks IM, get blood work, followed by 6 weeks subQ, get blood work, and determine for yourself if there is any palpable difference.

Yeah, I have great respect for Dr. Crisler. In a recent interview posted on YouTube, he talked about how 95% of his guys are very happy having switched to subcutaneous, but a small minority do not do well, and it's not clear why. Interestingly, in that same interview, he talked about the protocol he himself uses. He does subcutaneous T injections twice a week, and small amounts of beta HCG every day. He also uses Anastrozole twice a week. This is interesting because he is a very lean guy. Would he still have to use anastrozole if he wasn't injecting Sub-Q? I'm sure I don't know, but I'm sure Dr. Crisler knows.
 
Yeah, I have great respect for Dr. Crisler. In a recent interview posted on YouTube, he talked about how 95% of his guys are very happy having switched to subcutaneous, but a small minority do not do well, and it's not clear why. Interestingly, in that same interview, he talked about the protocol he himself uses. He does subcutaneous T injections twice a week, and small amounts of beta HCG every day. He also uses Anastrozole twice a week. This is interesting because he is a very lean guy. Would he still have to use anastrozole if he wasn't injecting Sub-Q? I'm sure I don't know, but I'm sure Dr. Crisler knows.

I think in order to answer that question, one would have to find out whether or not he was using an AI before he switched to subQ, and whether or not he changed anything regarding his protocol other than the injection site. Some people just aromatize a lot naturally, and the only way to control it is with anastrozole, lest their total T falls to sub-optimal levels in order to keep e2 in check without an AI. Others like Vince and Coastwatcher have managed to discover a sweetspot where they achieve the highest possible serum t levels without requiring additional estrogen management.
 

Dwhit

New Member
Wow, just wow. Paralysis by analysis of your own version of broscience. How about just seeing a Doctor who's already seen thousands of patients and has seen results of patients with daily subq injections instead.

Don't dis broscience, bro. The average guy on this forum knows more than most of the docs out there prescribing trt. I was first managed by a urologist colleague of mine at a major academic university. His protocol for me was 3000 iu HCG 3x/wk and anastrozole 1mg qday. He didn't even monitor my estrogen level! Fortunately I didn't stay with that guy very long. You are right that experience trumps everything, and I'm going to have everything monitored by someone who knows a heck of a lot more than I do. But in the meantime, my inner nerd cannot help but to think through the underlying physiology.
 
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Vince

Super Moderator
I think in order to answer that question, one would have to find out whether or not he was using an AI before he switched to subQ, and whether or not he changed anything regarding his protocol other than the injection site. Some people just aromatize a lot naturally, and the only way to control it is with anastrozole, lest their total T falls to sub-optimal levels in order to keep e2 in check without an AI. Others like Vince and Coastwatcher have managed to discover a sweetspot where they achieve the highest possible serum t levels without requiring additional estrogen management.
Correct me if I'm wrong. I believe Dr. Crisler has mostly always used Sub-Q and an AI.
 

hva

Member
On guitar forums, and specifically with regards to Fender Stratocasters, there has been an endless debate as to whether there is any difference in tone between a maple or rosewood fretboard. SubQ vs IM seems to be the TRT equivalent.

I've been sticking needles and injecting testosterone in different places on my body. Some days I feel like a rock star, some days like a greek god, and some days like a sack of shit. Where I stuck the needle and how deep doesn't really seem to correlate to those feelings whatsoever.

Personally, I like rosewood and I think it sounds a little warmer, but I also just like the way it looks and it's what I own so this may cloud my opinion.
 
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