IM vs Subcutaneous Testosterone Injections: What the Data Shows

0:09 Hey everybody, this is Hunter Williams. I hope you're doing amazing wherever you might be in the world. Today's video is going to be about the differences between intramuscular testosterone injections and subcutaneous testosterone. Spoiler alert, there's no right answer. I will interject with my own personal preferences throughout this video, and I'll go and tell you I prefer to do intramuscular testosterone injections. However, I think there is a use case for both of them. And what I want to use today is just cover some of the data that we have around both these methods, because believe it or not,

0:41 there's actually more than you would think around the pharmacokinetics and pharmacodynamics of how these work when injected intratumorally versus subcutaneously. So today I want to walk through the difference between those so that you can make the informed decision that's you need to make for your life about what would be best for you. I'll go and tell you, I prefer intramuscular injections. One, because of the way that I do them, every other day. So I typically do Monday, Wednesday, Friday, or Monday Wednesday Friday Sunday, Tuesday, Thursday, Saturday.

1:12 Kind of just depends on the week and if I'm traveling or whatnot. but I prefer that because when I'm doing that one, it's a pretty small volume that I've been injecting intramuscularly. So it not like a huge one ML size injection. It's usually a 30 or 25 to 30 units on a 28 gauge insulin syringe. And I can do that intromuscally and it doesn't hurt. Doesn't give me post-injection pain. As we're going to see today, I feel like I get better peak levels with that. But when when break those up into every other day injections, don't have too much of a trough.

1:42 Now when it comes to subcutaneous injections we'll look at this today. You may actually be better off if you're injecting less frequently to do subcutaneous because the distribution is going to happen more over time. Whereas you are going have a quicker peak and a quick trough with the intramuscular injections, which becomes less relevant when you do them every other day because you don't have time for it to troughs too low. That's what we're going to be talking about today. Again, I have no dog in the fight. Some people do better sub-Q, some people to do IM.

2:12 I prefer IM, but I will not sit ever in front of you guys and tell you there is only one definitive way to things, because almost all the time, there are multiple ways and there multiple types of people that do it better with different ways. That what will talk about the day. And as always, check out the email list down in description to make sure you're signed up for the e-mail list. With censorship on the rise, obviously I've had social channels shadow ban, deleted, you name it. That is the best way to stay in touch with me. And all I do with the email lists, I just send out helpful, informative emails, usually announcing new videos or other things that I'm working on that.

2:43 I will do write ups about sometimes it's future videos that do right ups on when I am just so excited to share things I haven't filmed the video on yet. But just make sure you're there. And before we get into things, it is holidays. It's actually Christmas Eve today. I'm going to release this on Friday, the day after Christmas. But thank you guys so much.I cannot tell you how much gratitude I have in my life that I get to do what I do. This is a dream come true. That I got to talk about these things and hopefully bring joy, education, and informative information to you, guys.

3:13 So thank, you it really means the world to me to get Without further ado, let's hop into the slides and today we're going to talk about IM versus sub-Q testosterone. And also too, we are going talk it for men and women. So today is not just for the men. All right, lets get into it today. We're gonna go over sub Q versus intramuscular testosterone injections. Were gonna look at these both for man and for women As always, just to start out with a little bit of a background, TRT treats androgen deficiency in men with hypogonadism and is often or occasionally prescribed off label for women.

3:44 And I hope, and one of my missions in life is to help bring that to more women because once women have hormonal decline, whether that's perimenopause, postmenopausal, they oftentimes require testosterone in order to be healthy. And again, the goal is to alleviate symptoms such as fatigue, low libido, reduced muscle mass, mood changes, and restore serum testosterone to normal physiological ranges. When we look at the delivery systems, obviously I'm a big fan of injections. Traditionally the TRT has been traditionally administered via intramuscular injections and sub-Q injections have emerged as a compelling alternative.

4:18 And today we're going to look in both routes, comparing formulations, pharmacokinetics, clinical outcomes, safety profiles, patient preferences. Now let's look at some common testosterone formulations. The most common injectable ones that you're gonna see prescribed are testosteronecipinate and testosteroneenanthate. And these have four to eight day half-life. the reason it's four and eight days is because some people burn through testosterone faster. So it was gonna be shorter for them. Some people it gonna longer. And in medical prescribing guidelines, you'll see these typically injected weekly or bi-weekly.

4:50 Now, obviously, like I said in the preface to this, I prefer every other day because if you're not doing that, there's a greater chance that you are going to have a higher peak and a lower trough, which obviously doesn't feel good. And then there is testosterone propionate. This is much less prescribed for long-term therapy due to the fact that you have to dose it frequently. And I've actually used testosterone proprionates a decent amount and even doing it the same dosing schedule of every other day. I actually feel better on sepinate or enanti. There is another one called testosterone on deconate and it's an ultra long acting formulation administered every 10 to 14 weeks requires deep intramuscular

5:27 injection with 30 minute observation for safety. That's used and has been used historically, but I'm not a big fan of that and I recommend you stay with it. Let's look at the pharmacokinetic differences of injections and how they can differ. With intramuscular, we have rapid absorption into vascular muscle tissue. With subcutaneous, We have gradual absorption, into adipose tissue with absorption through the lymphatic system. And with the intra muscular route, it deposits into the vacular muscle. There is a rich blood supply there that enables faster absorption.

5:59 Which means that we get higher initial peaks within 24 to 48 hours. We get muscle activity enhancing dispersion. So when we move around, via exercise or even something like foam rolling, we get more dispersion that is going to enhance it. With sub-Q route, it places a depot of testosterone into the subdermal fat tissue. What happens there is there a slower uptake via lymphatic circulation. And then what happens is we have a more gradual rise with a flatter curve, and then there's less variable absorption based on our physical activity.

6:31 And again, to go back to why I prefer intramuscular based, on the fact that I train with wakes and I do cardio, I feel like I get more circulation and activation of that testosterone when it goes into my muscle tissue. Then you also do get a little bit of sight enhancement, meaning that you can kind of notice that your muscles grow in the areas that you're injecting intramuscularly, which if you are inject into your glutes or to your delts, for most men and women, that's actually an area that they would prefer to have a little bit more muscle in. Let's look at the time to peak and stability.

7:03 With intra-muscular, we have an intravascular peak in 24 to 48 hours, and again, this is why I prefer inject every other day, because if I'm injectting every 48-hours, I've never necessarily like falling off of that peak that is in a therapeutic spot. But if we don't do that, so if were injecting once a week or once every two weeks, patients report energy surges post-injection followed by a decline before the next dose. And then when we look at sub-Q stability, the weekly sub Q injection maintains around 627 total level of testosterone with mild fluctuations throughout

7:34 the dosing interval and smaller, more frequent doses mitigate swings even with IM therapy. So whatever you do, I prefer to do every other day injections, even every day if you can. But if we're doing sub Q, you also want to that as well. Even though you could probably, if only wanted to inject once a week, I would say it would be better to sub-Q once week because you're going to have a flatter curve. Now let's look at the peak to trough ratio. So there's actually a 2022 study that compared 100mg of weekly testosterone sippingate intramuscularly versus 100 mg of testosterone enanthate subcutaneous

8:12 via an autoinjector pen and hypo gonadal men. And what do you know, they found that after 12 weeks, the mean testosterone level for men was 540, that did intramuscular, and then for sub-Q was 553. So for all intents and purposes, roughly the same, yes, sub Q is slightly higher. But both routes achieved comparable trough levels and equivalent total testosterone exposure, but I am produced significantly higher peaks, meaning that although the trough was about the same, the IM produced higher peaks, which some people may say is a bad thing and some may think is good thing.

8:48 I would say it's a good things if the peaks are not too pronounced and if troughs are too not pronounced. But it really depends on the person and how often they're going to inject. Obviously in this case it was just once a week, to which I'd probably say sub-Q would be better. Sub-q delivered a flatter release profile avoiding supra-physiologic concentrations. Intramuscular injections create higher peaks and deeper troughs, especially with infrequent or large doses, and sub-q produces more level concentration between injections, potentially reducing symptom variability. Again, when we see here once a week injection, I would say that the subq did better, but if we were crossing all of our t's and dotting all over our i's,

9:27 i would that intram muscular done every other day would be better than doing the Sub-Q every day. Let's look at clinical outcomes and efficacy. Both IAM and SUBQ effectively raise testosterone to therapeutic range and improve energy, libido, muscle strength, and sexual function. However, stable levels matter. More consistent testosterone delivery reduces the rollercoaster effects and patients report sustained well-being versus cyclical highs and lows. And then a pilot study showed all patients on a weekly SUBCU injection achieved peak and trough values within normal adult range.

10:00 Again, so when we look at SUPCU, we are getting the intended outcome at least as it stands on paper. That's a good thing, right? And I always will tell you that some testosterone is always better than nothing. We can get into the nuances of what's better or what worse, but here in this study, it was a pilot study. 100% success rate of getting men to therapeutic levels that they needed to be at. Symptom relief correlates with achieving Normal testosterone levels, which both routes accomplish effectively. The key advantage of sub-Q or frequent dosing is maintaining those levels consistently throughout the dosage interval.

10:33 There's one thing I wanted to talk about which is estradiol conversion. Now for a lot of people, this is like a naughty word and estridiol is bad. I am a firm opinion that estrdiol healthy for us at the right levels. We want our testosterone to aromatize into estrogen. we do not want to block that process. and I'm not gonna get into this for the scope of the video. However, there are differences in how testosterone aromatizes via the delivery method. Let's look at testosterone and how it converts into estradiol through aromatization.

11:05 Injection route influences this conversion via concentration peaks. With IM injections, we have higher peaks that produce more arometization, which lead to higher estridiol spikes. Now again, this is if we are doing intramuscular injections very infrequently, which for me would be once per week or even more inferequently. However, with SubQ injections, there's going to be a smoother delivery that reduces peak estradiol levels and both routes produce estrdiol within physiological range when dosed appropriately, but Subq reduces the risk of transient supraphysiologic estridiol level.

11:41 For men that experience what I would call high estrogen symptoms, some of them, not all of because in some cases it could be worse, but some do better with sub-Q injections. However, if the man has very high body fat and he's doing sub Q injections, a lot of times he will do worse because he's injecting testosterone into the inflammatory visceral fat, which is gonna cause a worse reaction that would oftentimes feel like a high estrogen reaction.

12:11 Again, I want to make this very clear because this is kind of a nuanced conversation. If you pound for pound said, what is going to aromatize less in a healthy body fat man, the subq will aromatize less. Now that is because the peak and trough is lower, meaning that the spikes are lower. However, if we were doing smaller, more infrequent intramuscular injections, in my opinion, you are roughly going to have the same amount of aromatization as you would with subQ, whether it was once a week or even if the Subq was every other day, just like your intra muscular injections.

12:48 we have to look at the data and the date it tells us that there's about a one-third lower amount of aromatization from sub-q than there would be intramuscularly. Again, for some men that could be the difference between them having very good tolerability of the testosterone versus having some of high estrogen symptoms. And again, I'm not going to get into that, but when we look a data that's out there, that what happens. Now, when we look at hematologic effects, which is basically how it affects our blood, testosterone stimulates red blood cell production and the effect

13:20 is dose and concentration dependent. With sub-Q injections, we noticed there are lower rises in hematochrit with sub Q versus IM and this stable release reduces excessive erythrocytosis risk. Now again, I don't want you to get afraid because intramuscular testosterone does not mean you're at risk for erythrocytosis. Yes, it will increase red blood cell count. yes, your hematocrit will likely go up. But as long as you are healthy, as Long as You are not inflamed, and as along as your exercising, you shouldn't have anything to worry about.

13:54 However, if that is something that you become concerned with because you're not living healthy. Then sub Q might be better. And when we look at it pound for pound, then this is just from the data because I'm gonna present the date to you as it is, with IAM injections, you typically see about a 6% rise in our hematocrit levels, which again, is not dangerous. However, was sub-Q, it's gonna be closer to 3%. Now for someone that is dealing with issues where hemato-crit would be relevant, maybe they have heart disease, something like that, sub Q might be more beneficial for that person if they are worried about that.

14:29 however, in most cases of relatively healthy men, IM will be completely fine, but I did want to throw that out there because it is something that we notice in the data when it's measured that there is less increase in hematocrit on sub-Q injections than there are intramuscular injections. But again, that doesn't mean that you have to through intra-muscular injection out. Now let's look at mood, cognitive, and sexual function. Obviously, normalizing testosterone improves mood confidence and concentration within four to eight weeks with most men and women and stable levels avoid

14:59 transient impairment during trough periods. When we look mood stability, frequent injections of either IM or subq or just infrequent sub q dosing reduces mood swings and irritability and patients report sustained well-being versus cyclical highs and lows. And for sexual function, both routes significantly improve libido and erectile function. There's no difference in sexual outcomes when comparable testosterone levels are achieved. I think this is an important point because maybe you would say that intramuscular is a little bit better for sex function because it's gonna give you a faster peak, but pound for pound, as long as your testosterone level are getting to where they need to be, your sexual functions is gonna improve.

15:35 It may look different, it may happen faster with intrabuscle versus sub-Q, you may have slightly better performance with intra-muscular versus a sub Q, But at the end of the day, it's going to be better as long as your testosterone is getting to the level it needs to. And in women, low-dose testosterone improves sexual desire, arousal and satisfaction, and the route matters less than achieving stable, therapeutic levels appropriate for female physiology. Now let's look at safety and tolerability with injection site reactions. Typically for intramuscular, what you're going to want to do is use a 28 to 29 gauge needle, half inch needle penetrating deep in the muscle tissue.

16:11 Some of the issues you can have from that are post-injection muscle soreness, bruising, or occasional hematoma and muscle fibrosis with the pre-used of same site. Now to avoid this what I would do work on fascial tissue, foam rolling, lacrosse balls, massage gun, things of that nature. And then rare complications, you could have an abscess, nerve injury, or significant pain limiting activity for one to two days. I think anyone that's done that has probably had at least some sort of pain. Now we look at sub-q, again, about the same size needle, I wouldn't want to go much smaller, like into the 30, 31 gauge,

16:45 just because it's gonna be harder to push the testosterone through that. but you could do that and you would do it into the ab or the thigh subcutaneously. Now the problem with subcu that I'm not a fan of is that about 14 to 15 percent of people report small nodules in the fat tissue which usually go away in one to two days and then you can have mild local irritation in fat tissues where it's injected. And again, the good thing about that is you don't tend to have the abscesses or some of the post-injection pain that you'd have intramuscularly.

17:16 When we look at systemic side effects and long-term risk, prostate health, there is no significant difference between routes on the PSA levels in men. So again not going to change anything in that level. Not that we should worry about at all, but there was no difference in PSa outcomes. Cardiovascular, again we talked about the hematocrit slightly being lower. or a lower increase in hematocrit, metabolic effects, both bypass liver metabolism. There are no liver concerns. And then with both, you will likely see a modest, very tiny reduction in HDL cholesterol, which can be improved through supplementation and lifestyle.

17:52 It's not so much that the benefits of testosterone therapy far outweigh the fact that with injections you can get a slight decrease in your HDl cholesterol. and both suppress HPG axis affecting fertility. DHT actually increases proportionally with both, so we don't see any differences usually in DHTs when measured. And then we will see slightly less aromatization out of the sub-Q in some cases. However, I did want to talk about this with sub Q. Again, i'm not making an argument for either one for you to do because you got to try.

18:24 I've tried both of these extensively and I have come to the conclusion that intramuscular is best for me. But I did want to talk about mast cell activation syndrome. So while generally well-tolerated sub-q testosterone injections may elicit more mast-cell type reactions, and here's why. Skin and subcutaneous tissues are rich in mast cells, which place the testosterone depot in a more reactive environment. And then when we have prolonged exposure, so slower subcute absorption means excipients stay in contact with mast cell dense tissue longer, which increase irritation potential.

18:54 And the reactions are often due to the carrier oils, especially if they're cottonseed or sesame, Which I would recommend you don't have. Usually grape seed or MCT is going to be the best. Or there could be preservatives like benzyl alcohol, or even something like purpling glycol rather than the testosterone itself that could cause a mast-cell reaction. And then shallow injections with micro depots, cold oil or high concentrations can amplify local irritation and mast cell activity. And the way to mitigate sub-Q reactions is obviously the technique, just do a shorter needle, use smaller volumes per site.

19:26 I personally don't like injecting more than like 20 units of testosterone sub Q because after that, again, you get that depo, which can be really annoying. Then consider switching carrier oils. Again, to use grape seed or MCT oil and make sure there's no excipients in there that would be harmful or cause issues. And again at the end of the day, if you have problems, IM will usually do much better. Now, just to compare, we have a chart here so we can look at the differences. With absorption, IAM is going to have faster absorption. Sub-Q is gonna be slower via lymphatic drainage.

19:58 Fluctuations, obviously with intramuscular larger peaks and troughs, especially if you're doing longer intervals. And the sub-q stable levels with minimal oscillation. Estradiol, higher E2 spikes, but again, that is usually in the case of longer injection intervals, and then sub-Q is going to have lower E2 aromatization. Hematocrit, greater hermeticrit rise, sub Q is gonna have less hermaticrit raise. Injection pain, you know, probably a little bit more injection pain with intramuscular than sub q, but then in subq you do have to deal with the nodules. Patient preference, again, it really is just up to you and what you prefer doing.

20:31 If you're lean, doing a small volume of an intramuscular injection usually doesn't bother most people. Then self-administration, obviously you can do both, both self and then advocacy. There's really, when you look at all the practical differences, nothing on paper that we can say one is definitively better. It's ultimately going to come down to personal preference. And again that's why I do these videos because even though there's no definitive answer for you, It helps to have an informed decision based on what might be good for Now looking at microdosing, I think much of medical practice will go towards this, which most smart people are doing this anyway,

21:05 but I'm just doing every other day or daily shots. And again, you could do that sub cue. Obviously, if you're doing a small volume, the smaller the volume the easier it is to do sub queue. obviously with every day other daily, we get near constant levels. We reduce the side effects like acne, mood swings, and it doesn't require us to have to these peaks and troughs. Let me look at men versus women. I just wanted to put on here the target levels. Typically, you're going to be up around 1,000 nanograms per deciliter for men.

21:35 For women, it's going be 100 to 200. Typical dosing is going 150 to 250, excuse me, 150, 200 milligrams weekly for man, and then 3 to 10 milligrams a weekly, for women and again, typically you are going see the same things. They respond pretty similarly to men when we talk about all these things. So everything I said really applies more to women than men, but just make sure that you're getting a concentration of the testosterone that is dose for a woman that allows you to inject intramuscularly.

22:05 A lot of times they'll give women a man's concentration, which is 200 milligrams per milliliter when they really need 20 milligrams for milliliters. And they will say, okay, well now just inject two units sub Q. and I really don't think you get therapeutic effect, especially if you were only doing that once per week. So not too much difference there from men and women. Now, when we look, just to sum up, both IM and sub-q effectively raise testosterone and improve symptoms when the right levels are achieved. With subq, we have more stable levels, lower E2 and hermetic rate increases, minimal pain.

22:37 And most people are just going to prefer that from a compliance standpoint. Obviously, who's not going want a sub q injection versus an intramuscular injection. But I personally would say that intra muscular injections when done every other day or even every day, have a much better feel than the sub-Q injections. And again, you got to do what's best for you. You got make sure you're getting your blood work done. you gotta make that you are experimenting with both to see what works best you, but that's what I would conclude works for me. And that is it for the slides. And those are the differences between sub-Q and intramuscular testosterone.

23:10 Again, this is not a video proselytizing to tell you to do one method versus the other. However, I think it is valuable to experiment with both. I've done both extensively and end of the day. I prefer every other day injections intramuscularly because I get more of a punch in the feel of how testosterone makes me feel good, but I also don't have the steep drop off that a lot of people that only inject once per week do. If I was only able to do once per week, I would probably do sub-q because it's going to have a lower peak and a, uh, lower trough that you would give it,

23:45 that would get if you were doing intramuscular once a week. Again, it truly up to you and your personal preference. I will say for someone that is a higher body fat than they need to be subq would be a better option because they don't have to inject through as much tissue to get to the muscle. However, you may have. A worse response because there's more, inflammatory tissue in the visceral fat that could cause a mast cell reaction or make people feel weird or feel like they have high estrogen symptoms.

24:15 However, when you're lean, doing sub-Q could be advantageous because you obviously will aromatize less, which in some cases might be better for some guys depending on how much they aromatize. But again, that's a different conversation for a day about arometization. I just want you to know that don't think about it. Aromatization is a bad thing. Think about is the necessary thing that helps confer protection alongside our testosterone. That's it for this one. Thank you guys so much. And again, just with the wrap up of the year, I cannot tell you how grateful I am to be in the position I'm to bring this information to you,

24:45 guys. You make this worth doing. All of messages, support, the comments, everything like that. Whatever shape or fashion that you support me, whether it's liking, commenting, subscribing, sharing this with your friends, using my code at places, or just spreading the word in general. I can't tell how far that goes in supporting me. So thank you. I promise that does not go unnoticed. And I just want you guys to know from the bottom of my heart, I have so much gratitude for you out there helping shape the future of this movement where

25:15 we talk about hormones and peptides and living our healthiest, best life. Thank you, guys, so, much. I hope you have an awesome day wherever you're at and I'll talk to you in the next one. Peace.