TRT and Collagen Synthesis

[Foreigner]

What I know is that Testosterone does suppress collagen production, but in practice this gets balanced by Estradiol when you're on TRT, as some of your Test will be aromatised into Estradiol.

This goes out of the window when you use higher dosages, AIs (aromatase inhibitors), or compounds that do not aromatise at all (DHT derivatives) or very little (Nandrolone) or aromatise to weaker Estrogens like Boldenone.
To be considered also that people convert Test to DHT at different rates and DHT is a very strong androgen it has a negative impact on tendon structure.

Anecdotally, adding 120mg Nandrolone Decanoate to my 150mg TRT for 2 months took over 5 years of the appearance of my skin, thicker, more elastic, wrinkles filled up, pores shrunk.

Rather than this being a direct action of Nandrolone, I speculate this is due to the 5 alpha reduced version of Nandrolone, DHN, being a very weak androgen reducing the androgenic load on my skin by competing for ARs (androgen receptors) with DHT.

IME, AAS that will age your skin fast are Masteron and Proviron.

Well, I'm just looking at TRT, not these other AASs.

The effect on joints surely has to do with an individual's hormone metabolism. Some pump out more estrogen per quantity of DHT while in others DHT dominates. I agree that aromatization to estrogen is probably what protects the joints, whereas DHT dominance would cause joint issues. DHT tends to support "dry mass" while estradiol supports "wet mass".

The use of AIs is tricky because too much estradiol isn't good, but most of the time this can be managed with proper T levels. The issue is, what is "normal T". Most of the TRT clinics advise patients to get to the upper limit of normal and stay there. Some guys might not need that much, but a lot of the TRT clinics now are pushing that model. If your natural levels sit below 30 nmol (14-30 is normal range) then TRT bringing you to 30 nmol may cause estrogen spillover, in which case some AI use may be called for.

The main thing I'm gleaning from all my reading is there are still so many unknowns... but that things are definitely better than 20 years ago.

I just wish I knew for sure if TRT intrinsically puts one at risk of joint issues or if it's all a product of over-extending oneself due to the strength/drive granted by T.

Seems like there is a variety of data on the subject, for instance, this is suggesting that it increases it:

"[H]igh doses of anabolic androgenic steroids enhance collagen synthesis especially in soft connective tissues, possibly through reversing the action of glucocorticosteroids on collagen metabolism."

https://www.google.com/url?sa=t&source=web&rct=j&url=https://paulogentil.com/pdf/The%2520Effect%2520of%2520Supraphysiological%2520Doses%2520of%2520Anabolic%2520Androgenic%2520Steroids%2520on%2520Collagen%2520Metabolism.pdf&ved=2ahUKEwjZmIzom-v-AhVMIEQIHcYrAX44FBAWegQIGRAB&usg=AOvVaw2uLRAnXnU550qdF6ZDoZs2

I think that much like how other hormones work (i.e., where different concentrations of a given hormone have starkly different effects), the effect of testosterone on collagen synthesis almost certainly isn't as simple as it "decreases (or increases) collagen synthesis".

I agree, it's not probably as simple as a 1:1 statement about T itself. Probably depends on its metabolic relationship to an individual's hormone cascade.

That may also be why some studies say yes and others no to the collagen connection.

There do seem to be a disproportionate number of complaints about joint issues in the TRT community though. However, it's hard to teeze out the variables because a lot of these guys are weight lifting. I've tried making posts directed at TRT users who don't engage in heavy weight lifting but the meat heads always end up replying.

 

[sekio]

Normal levels of testosterone in men are 300 to 1000 ng/mL.
Aromatase naturally produces estrogen levels at... 10 to 40 picograms per mL. Picograms are 0.001 nanograms, so you are looking at a ratio of between 0.01:300 to 0.04:1000, or 1 part estrogen to 25,000-30,000 parts testosterone in a normal individual. To me, this suggests a minor role if any for the estrogen produced in a man. (But by no means is it unnecessary.)
I would imagine you need seriously heavy doses of T before aromatase and estrogen production becomes an issue. Honestly in this day and age it's a safe bet that random xenoestrogens from food probably have more estrogenic effect, and even that is mild at best.

The effect on joints surely has to do with an individual's hormone metabolism. Some pump out more estrogen per quantity of DHT while in others DHT dominates.

It is worth noting that testosterone produces different effects in different tissues: some tissues are rich in 5a-reductase and have elevated levels of the more potent DHT. Some other tissues express more aromatase, likewise.
This is why some steroids have different effects and only some will form estrogen analogues, while others wont.

The issue is, what is "normal T". Most of the TRT clinics advise patients to to the upper limit of normal and stay there.

This may be a reason to have your hormones managed by a doctor or endocrinologist. After all there is an unwritten myth among many men that "more testosterone is always better" because it makes you more virile, muscular, "manly", etc., and because they are selling a service, catering to your ego pays off.
That said even at the top levels of "normal" I would not expect any side effects typical of steroid abuse or elevated estrogen. It takes significantly larger doses of T to cause estrogen to be a problem.
I have not heard of e.g. gynecomastia from medically reasonable uses of testosterone to provide replacement therapy, but rather from frequent, large dosing. And with regular blood testing, detecting elevated estrogen can be done before it starts producing longer-term negative effects, and the testosterone dose adjusted downwards as necessary.

And aromatase inhibitors are never prescribed in TRT where I'm from, either.
Theoretically speaking, a testosterone deficiency will also correspond to an estrogen deficiency too, and restoring normal levels of T will also normalize the (much smaller, but still important) levels of estrogen too.

 

[Genetic Freak]

Is there like a precursor to testosterone, instead of adding T perhaps using the thing that actually creates and accelerates testosterone?

Saturated fat contains cholesterol, the precursor to testosterone...

 

[Genetic Freak]

Seems like there is a variety of data on the subject, for instance, this is suggesting that it increases it:

"[H]igh doses of anabolic androgenic steroids enhance collagen synthesis especially in soft connective tissues, possibly through reversing the action of glucocorticosteroids on collagen metabolism."

You are correct, steroids do increase the production of collagen, but its matrix is compromised, leading to stiffening and potential rupture...

 

[Phobos]

I just wish I knew for sure if TRT intrinsically puts one at risk of joint issues or if it's all a product of over-extending oneself due to the strength/drive granted by T.

I would say that at least for some people that (being more enthusiastic in your physical efforts) is a risk factor.
You are likely to become a bit stronger and effort will feel more fun than before IME.

 

[G_Chem]

"Natural T" won't help you if your levels are chronically low. Low T is just as a bad as T that's too high. Yes, I would rather rely on exogenous T for the rest of my life than have the problems associated with low T.

No offense but you should not be offering steroid advice in a thread like this when you are clearly operating on outdated/stereotyped information. It's attitudes like yours that have perpetuated MDs never prescribing T for men who really need it. Not to mention your opinionated responses are irrelevant to what I asked.

It’s funny that you didn’t even read my post.. Instead respond emotionally, if you want to rely on exogenous T that’s all you bud.

Notice how I said “and when all that fails does someone begin to think about it.” If you had good reading comprehension skills you’d see I’m not saying someone shouldn’t. But only after you’ve exhausted methods to naturally raise your T. There are people that eat garbage all day, hardly workout, take all sorts of drugs and then instead of actually fixing all that just resign themselves to exogenous T. FOR LIFE.. I love how that always gets glossed over.

This is a harm reduction forum. The safest course of action is to first try the things that we know get T production going. And btw, I’m someone who should be majorly struggling with T based on the cancer I had, the chemo I went through, opiates, cannabinoids, etc.. At one point I did have low T. But through hard work have been able to naturally get my levels back to a good place in the mid 600’s for total T. Low T doesn’t mean low T forever, but obviously (as I said) if one has exhausted all options and still struggling..

So ya man no offense but next time read my post before getting all offended thinking that I’m downing on folks like I’m yourself. That was your decision, good for you. But that’s not for everyone.

-GC

 

[Genetic Freak]

Reading some of the user reports online, they'll talk about the levels of T they're pushing + their daily lifts and I'm like... are you sure it's the T affecting your joints and not your insane lifts?

However... there is concern that, while T amps up protein synthesis, it downgrades collagen synthesis. So muscle development begins to outpace tendon/ligament regeneration. Hence the joint inflammation. T for sure supports synovial fluid + the capsule, so the proposed negative effects are all tendon/ligament which points to either a collagen issue or a "lifting too much weight" issue.

I am having difficulty locating reports of non-weight lifters on TRT saying they have joint issues. It's mostly the lifters saying it.

However, the studies are neither here nor there.

Remember we are discussing replicating normal physiological levels of testosterone with bioidentical hormone replacement.
Side effects commonly associated with supraphysiological doses shouldn't apply...

 

[sekio]

Testosterone cypionate is one of the first therapies recommended to treat low T for a reason. It is cheap, widely available, and a once per week IM injection produces the same end result that (in some cases) takes large amounts of effort and lifestyle changes, some of which may be difficult or impossible to do regularly - for instance, as a paraplegic I am not going to be able to do many exercises, and spasticity will limit those that I can do. As for diet, not everyone has the funds to eat ideally nutritive meals, or the time/equipment/skill to prepare them. Drug use, the same - chronic pain patients are not going to discontinue their opioids to recover testosterone levels.

I am happy you managed your low testosterone non-pharmacologically, but to expect everyone to do so the same way, and suggesting that exogenous supplementation is some sort of disreputable action or indicates a personal failing of some sort is harmful at worst and insulting at best. There is nothing at all preventing someone from making the lifestyle improvements they feel comfortable doing after normalizing their T levels, and indeed it may be easier to do so.

 

[Foreigner]

Remember we are discussing replicating normal physiological levels of testosterone with bioidentical hormone replacement.
Side effects commonly associated with supraphysiological doses shouldn't apply...

I hear you... but I think synthetic T has a different effect on the body than bioidentical T or endogenous T. For example, there is no known cancer risk to endogenous T, but exogenous T has a higher 10 year cancer risk. Similarly, I think in some people, exogenous T may be more likely to aromatise than their endogenous T.

Assuming the collagen connection isn't about lifting habits, then I'm wondering if it's just exogenous T in general that is causing problems, regardless if supraphysiological or not.

 

[Foreigner]

Testosterone cypionate is one of the first therapies recommended to treat low T for a reason. It is cheap, widely available, and a once per week IM injection produces the same end result that (in some cases) takes large amounts of effort and lifestyle changes, some of which may be difficult or impossible to do regularly - for instance, as a paraplegic I am not going to be able to do many exercises, and spasticity will limit those that I can do. As for diet, not everyone has the funds to eat ideally nutritive meals, or the time/equipment/skill to prepare them. Drug use, the same - chronic pain patients are not going to discontinue their opioids to recover testosterone levels.

I am happy you managed your low testosterone non-pharmacologically, but to expect everyone to do so the same way, and suggesting that exogenous supplementation is some sort of disreputable action or indicates a personal failing of some sort is harmful at worst and insulting at best. There is nothing at all preventing someone from making the lifestyle improvements they feel comfortable doing after normalizing their T levels, and indeed it may be easier to do so.

Thank you. Years of corticosteroid use and HPA axis suppression have affected my T levels, in combination with getting older. My chronic illness and my lower T are definitely connected.

I didn't want to make this thread about me personally, I just wanted to discuss the facts of T and collagen, which should be possible without having to personalize everything. But as usual some people enjoy the opportunity to come into my threads and shit talk while offering no expertise, as if this is the lounge.

 

[Foreigner]

You are correct, steroids do increase the production of collagen, but its matrix is compromised, leading to stiffening and potential rupture...

Do you have a study to back this up? Not that I don't believe you, I just want to read more. Your response here seems very definitive and I want to know how you arrived at that. So far I am getting very mixed info from the studies.

 

[Foreigner]

Normal levels of testosterone in men are 300 to 1000 ng/mL.
Aromatase naturally produces estrogen levels at... 10 to 40 picograms per mL. Picograms are 0.001 nanograms, so you are looking at a ratio of between 0.01:300 to 0.04:1000, or 1 part estrogen to 25,000-30,000 parts testosterone in a normal individual. To me, this suggests a minor role if any for the estrogen produced in a man. (But by no means is it unnecessary.)
I would imagine you need seriously heavy doses of T before aromatase and estrogen production becomes an issue. Honestly in this day and age it's a safe bet that random xenoestrogens from food probably have more estrogenic effect, and even that is mild at best.

The info I've looked at (and nothing is set in stone) says the ratio is 20:1 T:E, but some men are more E dominant so this ratio will not always be true. Also, more adipose tissue increases aromatization. A lot of men who start TRT are overweight as part of their low T symptoms, so when they first start TRT they produce more estrogen than they eventually will once their body fat % is under control. Also, a lot of men on T also take HCG to maintain testicular function (avoid shrinking balls, infertility, etc.) so some nominal amount of endogenous T will also be occurring even on TRT. So if that's the case (which it would be in my case), then it's not just T we're looking at, but residual endogenous T as well.

This may be a reason to have your hormones managed by a doctor or endocrinologist. After all there is an unwritten myth among many men that "more testosterone is always better" because it makes you more virile, muscular, "manly", etc., and because they are selling a service, catering to your ego pays off.
That said even at the top levels of "normal" I would not expect any side effects typical of steroid abuse or elevated estrogen. It takes significantly larger doses of T to cause estrogen to be a problem.
I have not heard of e.g. gynecomastia from medically reasonable uses of testosterone to provide replacement therapy, but rather from frequent, large dosing. And with regular blood testing, detecting elevated estrogen can be done before it starts producing longer-term negative effects, and the testosterone dose adjusted downwards as necessary.

I agree with this. However, I'll say that the medical system in Canada is mostly garbage. My MD is very open minded and is willing Rx T based on my health history. Most doctors don't Rx T and if they do they will only give you 100mg every 2 weeks based on an automatic protocol, which is absurdly low. The endocrinologist I saw behaved this way. Had no care in the world that my original T levels were naturally higher (not above normal but high normal). She just wanted to give a standard amount and call it a day. After endogenous suppression kicks in, I would have lower T than when I started. Fortunately my regular MD is more versed. This is all to say that seeing an MD or endo in Canada is not likely going to get you what you need, which is why people are going to private TRT clinics now.

But like I said already... I think synthetic T (like cypionate) might have different effects on the body than bio-ID T at any dose. And I wonder if that's where the collagen piece comes in.

And aromatase inhibitors are never prescribed in TRT where I'm from, either.

Most the TRT clinics keep AIs as an option, especially where obesity is involved. The public health system in Canada mostly has steroid knowledge from the 1990s. It's pretty bad. I've talked to guys who can't get the doses they need because doctors are told to not give more than 100mg/2wks.

Theoretically speaking, a testosterone deficiency will also correspond to an estrogen deficiency too, and restoring normal levels of T will also normalize the (much smaller, but still important) levels of estrogen too.

Yes definitely, this logic is sound, but like I said above, the ratio can be affected by factors like adipose tissue. Not everyone aromatizes in a predictable fashion. I think personally my body follows a more predictable pattern though, and I'm not overweight. I'm not convinced that synthetic T works the same as natural T in a 1:1 way though. That's why I'm wondering why TRT affects collagen so bad.

 

[Foreigner]

I would say that at least for some people that (being more enthusiastic in your physical efforts) is a risk factor.
You are likely to become a bit stronger and effort will feel more fun than before IME.

My assumption is that if TRT brings me back to my normal level then I won't be having "fun" anymore than I would have back when my T was at that range. I just miss being healthy. Chronic illness has really ravaged my body.

 

[Genetic Freak]

Do you have a study to back this up? Not that I don't believe you, I just want to read more. Your response here seems very definitive and I want to know how you arrived at that. So far I am getting very mixed info from the studies.

I'm quoting from a personal discussion I had with my Orthopedic Surgeon several years ago..

Anecdotally I have previously experienced several tendon ruptures, and many minor to severe tears over the last 46 years of lifting whilst using supraphysiological doses of exogenous compounds..
I might add, strength gains seem to become apparent quicker than tendons can catch up. There can be a tendency to push personal bests before tendons might be fully ready.. This might be a significant factor in tendon rupture when using supraphysiological amounts of hormones..
I am currently recovering from a rupture atm..

 

[Genetic Freak]

The info I've looked at (and nothing is set in stone) says the ratio is 20:1 T:E, but some men are more E dominant so this ratio will not always be true. Also, more adipose tissue increases aromatization. A lot of men who start TRT are overweight as part of their low T symptoms, so when they first start TRT they produce more estrogen than they eventually will once their body fat % is under control. Also, a lot of men on T also take HCG to maintain testicular function (avoid shrinking balls, infertility, etc.) so some nominal amount of endogenous T will also be occurring even on TRT. So if that's the case (which it would be in my case), then it's not just T we're looking at, but residual endogenous T as well.



I agree with this. However, I'll say that the medical system in Canada is mostly garbage. My MD is very open minded and is willing Rx T based on my health history. Most doctors don't Rx T and if they do they will only give you 100mg every 2 weeks based on an automatic protocol, which is absurdly low. The endocrinologist I saw behaved this way. Had no care in the world that my original T levels were naturally higher (not above normal but high normal). She just wanted to give a standard amount and call it a day. After endogenous suppression kicks in, I would have lower T than when I started. Fortunately my regular MD is more versed. This is all to say that seeing an MD or endo in Canada is not likely going to get you what you need, which is why people are going to private TRT clinics now.

But like I said already... I think synthetic T (like cypionate) might have different effects on the body than bio-ID T at any dose. And I wonder if that's where the collagen piece comes in.



Most the TRT clinics keep AIs as an option, especially where obesity is involved. The public health system in Canada mostly has steroid knowledge from the 1990s. It's pretty bad. I've talked to guys who can't get the doses they need because doctors are told to not give more than 100mg/2wks.



Yes definitely, this logic is sound, but like I said above, the ratio can be affected by factors like adipose tissue. Not everyone aromatizes in a predictable fashion. I think personally my body follows a more predictable pattern though, and I'm not overweight. I'm not convinced that synthetic T works the same as natural T in a 1:1 way though. That's why I'm wondering why TRT affects collagen so bad.

Also, more adipose tissue increases aromatization.

You are correct, the aromatase enzyme that converts testosterone to estrogen is found primarily in adipose tissue..

Also, a lot of men on T also take HCG to maintain testicular function (avoid shrinking balls, infertility, etc.)

I might consider hCG as an option for TRT on its own, as opposed to including it as part of a TRT regime. Reason: Although hCG might induce some endogenous response, its believed when combined with TRT the extra oxidative stress inside the testes may cause damage..

100mg every 2 weeks

100mg of product (Cypionate) is about 65mg of actual testosterone, when you take into account compounded half lives 5-6 days (from memory I could be wrong)
blood plasma levels are quite favourable after 4.5 half lives.. (60+mg over 5-6 days)..

I think synthetic T (like cypionate) might have different effects on the body than bio-ID T at any dose.

I might be inclined to agree, endogenous testosterone is released in small pulsatile doses, I believe twice a day, which keeps blood plasma spikes to a minimum.
One high dose injection every 1-2 weeks induces a different response, and creates a much higher initial plasma spike, which could be the problems previously discussed..

I'm wondering why TRT affects collagen so bad.

I'm not sure it will, if dose is titrated correctly ie: twice weekly small doses...

 

[RedRum OG]

Reading some of the user reports online, they'll talk about the levels of T they're pushing + their daily lifts and I'm like... are you sure it's the T affecting your joints and not your insane lifts?

However... there is concern that, while T amps up protein synthesis, it downgrades collagen synthesis. So muscle development begins to outpace tendon/ligament regeneration. Hence the joint inflammation. T for sure supports synovial fluid + the capsule, so the proposed negative effects are all tendon/ligament which points to either a collagen issue or a "lifting too much weight" issue.

I am having difficulty locating reports of non-weight lifters on TRT saying they have joint issues. It's mostly the lifters saying it.

However, the studies are neither here nor there.

Also test increases strength, which is bad for joints. I think this is the true culprit. What do you expect putting 100lb on your deadlift in 2 weeks?

I've been on TRT ~6years, juicing for ~3 years before that, even did some amateur powerlifiting, and as of now, in my early 30s never had a single injury (thank you, sweet universe)

Anecdotal, but if supraphysiologicol doses of gram+/week aren't immediate tendon killers, I can't imagine TRT is. The factors for your risk would be mostly workout routine and genetics. Stretch, don't ego lift like a idiot, and listen to your body

 

[sekio]

This is all to say that seeing an MD or endo in Canada is not likely going to get you what you need, which is why people are going to private TRT clinics now.

Well, as a Canadian, how it worked for me was, a blood panel showed severe deficiency of testosterone, I was put on 100mg cyp weekly, two weeks or so another blood test was done and my dose adjusted to 80mg, then another test 2 weeks later, and then I was given an Rx for 1000mg multidose vials of Depo-Test refilled every so-and-so weeks, and left to my own devices
Mind you I had an endocrinologist who was doing his job and not just giving one size fits all Rxs with no testing at all.

One high dose injection every 1-2 weeks induces a different response, and creates a much higher initial plasma spike, which could be the problems previously discussed..

I'm pretty sure the ester hydrolysis is gradual enough that there are not really major spikes and more of a steady state level achieved over time.

 

[Foreigner]

Thanks everyone for the replies. This has been very useful.

 

[Serotonin101]

I hear you... but I think synthetic T has a different effect on the body than bioidentical T or endogenous T. For example, there is no known cancer risk to endogenous T, but exogenous T has a higher 10 year cancer risk. Similarly, I think in some people, exogenous T may be more likely to aromatise than their endogenous T.

Assuming the collagen connection isn't about lifting habits, then I'm wondering if it's just exogenous T in general that is causing problems, regardless if supraphysiological or not.

Natural androgens have peaks and troughs as opposed to androgen therapy. However there are many studies to demonstrate that low testosterone increases risk for various cardiovascular disease symptoms such as HDL-C decreasing, increased triglycerides, unfavorable BMI, etc.
Nothing is without risk so it's one of those things where "which is more concerning to you?" potential of cancer or potential for cardiovascular disease?

 

[Foreigner]

Natural androgens have peaks and troughs as opposed to androgen therapy. However there are many studies to demonstrate that low testosterone increases risk for various cardiovascular disease symptoms such as HDL-C decreasing, increased triglycerides, unfavorable BMI, etc.
Nothing is without risk so it's one of those things where "which is more concerning to you?" potential of cancer or potential for cardiovascular disease?

The cancer risk of normal levels of TRT seem to be negligible, so I am more inclined toward TRT than I am living with low T.