Subcutaneous Administration of Testosterone

[JSayaMD]

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.

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.

Per Nelson's post, do you have this study Dr John?

 

[JSayaMD]

Nelson, what's the current status on the undecanoate approval here in the US? Last I heard they had some over exaggerated concerns about injection site reactions, oil embolisms, etc...

Dr Saya

 

[JSayaMD]

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.

I tend to agree, Nelson. In practice, as you may know, the majority of my patients indeed do quite well with once weekly or q5-6 day IM injections. I do not necessarily agree with your statement that most men are too busy to do twice weekly injections. For those patients of mine who either need twice weekly injections or prefer twice weekly injections, they seem to have no issues with sticking to that routine. An intramuscular injection takes five minutes at the most...first thing in the morning or just before bed, most guys will have no difficulty fitting that into their schedule. Now if this were the good old days when you had to actually go to your physicians office to have your injection done, then that obviously would be a different story. With those guys that need or prefer twice weekly injections, what I do find to be more challenging then the actual time commitment involved is actually remembering to do the twice-weekly injections. I tell my guys it is "six of one" and "a half a dozen of the other" and what works for one doesn't necessarily work for another.

Dr Saya

 

[Dr. John Crisler]

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

...that's why I like to add in daily HCG shots. The body then produces the saw tooth pattern. And many other benefits as well.

You simply can not get enough T in to overcome higher SHBG by splitting a weekly dose. Not without prescribing too much.

 

[Dr. John Crisler]

I tend to agree, Nelson. In practice, as you may know, the majority of my patients indeed do quite well with once weekly or q5-6 day IM injections. I do not necessarily agree with your statement that most men are too busy to do twice weekly injections. For those patients of mine who either need twice weekly injections or prefer twice weekly injections, they seem to have no issues with sticking to that routine. An intramuscular injection takes five minutes at the most...first thing in the morning or just before bed, most guys will have no difficulty fitting that into their schedule. Now if this were the good old days when you had to actually go to your physicians office to have your injection done, then that obviously would be a different story. With those guys that need or prefer twice weekly injections, what I do find to be more challenging then the actual time commitment involved is actually remembering to do the twice-weekly injections. I tell my guys it is "six of one" and "a half a dozen of the other" and what works for one doesn't necessarily work for another.

Dr Saya

I tell my guys if they aren't willing to spend just a few minutes each week on their hormonal regimen, I promise I won't spend any time staring at the ceiling at night trying to figure out what to do next.

LOL

 

[Dr. John Crisler]

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.

I agree MOST men do just fine on a weekly injection of test cyp, or daily BigPharma T gel. Nothing more.

That point is important because we are still in a hearts-and-minds war to get other doctors to prescribe TRT in the first place.

However, for the tough cases--and almost half are--we need to dig in a little further.

IMPO testosterone undecoanate is the wrong direction to move. It will take many, many months to properly tune up a patient...and they come in wanting to be tuned up like YESTERDAY.

The above's serum androgen profile will be nearly flat line. Perhaps a daily HCG injection on top will make things much better.

What I am always talking about is taking guys to the cutting edge. Not what is enough to just get by.

 

[Dr. John Crisler]

Per Nelson's post, do you have this study Dr John?

The gents were kind enough to repost them for me at the FB blog. Would someone be kind enough to do tha again, please?

I added them to my "TRT: A Recipe for Success" lecture. Also writing an article on the subject for the AMMG's monthly newsletter.

 

[Dr. John Crisler]

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.

We are all drooling at the thought!

Well, we geeks are. LOL

 

[JSayaMD]

I agree with Dr John's concern over timeframe for adjusting/optimizing patient's T levels with undecanoate. It is somewhat similar to the pellet method of TRT... Once you place the pellets or take the undecanoate injection, it's there ...and it's there for a LONG time. This makes it more challenging to "dial-in" the dosing in a timely manner. There are pros, but that is certainly a con. As I stated, there is NO perfect method as of right now, but whomever develops that perfect method will be a very happy (wealthy) individual and there will be many happy patients.

Dr Saya

 

[Nelson Vergel]

Injection Fatigue and Future of TRT Market

The only winners in this race of clinics and pharma will be those that optimize treatment simplification. In my world we have gone from 6 times a day dosing down to 1 time a day in a decade. In three years we will have nano formulations that can be injected once a month.

Human beings without chronic illnesses (except for hypogonadism, if you even want to classify it as a chronic condition) are not meant to inject frequently. Studies I have posted here have shown low adherence rate even in patients using something as simple as a daily gel.

Only a small fraction of the men health market will be driven by clinics that advocate for men to inject more than once (T, HCG, others). Only highly motivated and driven men (which are a minority) will adhere to that lifestyle. Many will start programs that will then be abandoned due to what is called injection fatigue.

Anyone not looking at treatment simplification will eventually not be part of the men's health market. I give it less than 5 years before pharma takes over long acting formulations that will wipe out the current clinics that preach 4 injections a week. It will start with testosterone undecanoate and move beyond that.

 

[Nelson Vergel]

Update on Aveed (Nebido- testosterone undecanoate- long acting testosterone)

Update on Aveed (Nebido- testosterone undecanoate- long acting testosterone):

After a few problems with the FDA review process that have slowed down its approval by 3 years, this was the last announcement:

"Endo Pharmaceuticals Inc., a subsidiary of Endo Health Solutions Inc. (Nasdaq: ENDP) announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the complete response submission made by Endo to the new drug application (NDA) for its long-acting testosterone undecanoate injection, Aveed, intended for men diagnosed with hypogonadism. In connection with the acceptance, the FDA assigned Endo's NDA a new Prescription Drug User Fee Act (PDUFA) action date of Feb. 28, 2014."

 

[indydaddy]

I'm going to try it after nearly 20 years of weekly I.M. injections with lots of scar tissue. My problem is I have no sub-Q fat.

 

[Nelson Vergel]

indydaddy, I have the same two issues

 

[robs2nd75]

Can't wait to see how much they are going to charge.

 

[Dr. John Crisler]

The only winners in this race of clinics and pharma will be those that optimize treatment simplification. In my world we have gone from 6 times a day dosing down to 1 time a day in a decade. In three years we will have nano formulations that can be injected once a month.

Human beings without chronic illnesses (except for hypogonadism, if you even want to classify it as a chronic condition) are not meant to inject frequently. Studies I have posted here have shown low adherence rate even in patients using something as simple as a daily gel.

Only a small fraction of the men health market will be driven by clinics that advocate for men to inject more than once (T, HCG, others). Only highly motivated and driven men (which are a minority) will adhere to that lifestyle. Many will start programs that will then be abandoned due to what is called injection fatigue.

Anyone not looking at treatment simplification will eventually not be part of the men's health market. I give it less than 5 years before pharma takes over long acting formulations that will wipe out the current clinics that preach 4 injections a week. It will start with testosterone undecanoate and move beyond that.

I could not disagree more.

I would definitely call hypogonadism a chronic condition. What condition could possibly be more chronic than this? It affects every single cell in the body, and makes us sick, weak, depressed, impotent, and die younger.

It also happens to be the most underdiagnosed, and therefore untreated, malady today. In fact, many--in spite of thousands of studies to the contrary--do not even think it is an issue!

The desire to simplify treatment is a false complaint. First, we have to figure out HOW to treat. Then we will work on the rest.

Just because you do not have any serious issues complicating your personal TRT regimen (and everyone is glad for that) does not mean others do not as well. In fact, at least 1/4 of all men who suffer hypogonadism (just my best guess at this point, by my own clinical experience) are "complicated" cases requiring more, sometimes much more, expert analysis and treatment.

We are not making this more complicated for the simple desire to do so! What we do, we do because this is a brand new area of medicine, and we have only begun to scratch the surface. Patient after patient after patient come before us, and bewilder us. Are you suggesting we stop expanding our skills, and abandon all hope of treating everyone?

If your particular situation easily resolves, then your average local PCP can surely handle it. But IF there are estrogen, SHBG, receptor, PFS, hyperexcretion, hypermetabolization, etc etc issues, then you can either seek the guidance of a well-practiced expert, or die young and unhappy.

In short, if a one-size-fits-all, cookie cutter approach is the way to go, there isn't much point in being here.

I really do not like looking down our noses at those who have more complicated issues. They are just trying to be healthy and happy, too, and deserve to be. just like everyone with a medical condition.

Going to the gym is a real hassle. In fact, it is much more time, effort, and expense costly than any TRT regimen. But one must do it. It's just how a man lives.

...the same goes for the other things he must do to be healthy and happy. Like his TRT regimen.

And it is harder to eat right. All that cutting and chopping and so forth.....

 

[Dr. John Crisler]

I'm going to try it after nearly 20 years of weekly I.M. injections with lots of scar tissue. My problem is I have no sub-Q fat.

try the fat pads on top of your glutes. I do.

IF there is none, then go back to poking holes in your muscles. There is no choice, other than to switch to gels.

 

[Dr. John Crisler]

For some strange reason, the words "cookie cutter" become a link that goes to cooking equipment.

 

[JSayaMD]

For some strange reason, the words "cookie cutter" become a link that goes to cooking equipment.

LOL...it is so the readers can look for better cooking equipment to make it easier for them to do all of that "cutting and chopping and so forth" so they can eat better!

All jokes aside, I agree with you in principle on this one. Hormonal treatment, and TRT in general, with all of the intricacies involved do not commonly lend themselves well to simplistic approaches - no matter how convenient they may be. In fact, the MAJORITY of my patients that come to me from other clinics come to me for exactly that reason... the other clinic's approach was TOO simplistic. The other provider did not have an appreciation for the "finer" aspects of TRT/HRT.

Should patients be injecting themselves multiple times unnecessarily? Of course not, but if, based on a comprehensive consultation AND thorough discussion about alternative options, it is mutually decided (between patient and provider) that a more complex (ie: more time-consuming or more demanding) regimen is ideal, then that is the regimen they should be on. If the patient is agreeable (and is empowered and educated that they have a say in the treatment) they are much MORE likely to remain compliant with ANY treatment regimen - no matter how complex it may be.

Time will tell, no doubt big pharma will do their part, but IMPO nothing replaces seeing a qualified provider who has experience and knowledge in this area and can develop a CUSTOMIZED and MODIFIABLE (because as we know things often change and require adjustments) treatment plan. Not saying it will, but if left to big pharma, convenience + simplicity will = cookie cutter, and we all should then go buy that cooking equipment because it will NOT be good for anyone!

Dr Saya

 

[Gene Devine]

For some strange reason, the words "cookie cutter" become a link that goes to cooking equipment.

^^^^That made me laugh out loud

 

[Gene Devine]

LOL...it is so the readers can look for better cooking equipment to make it easier for them to do all of that "cutting and chopping and so forth" so they can eat better!

All jokes aside, I agree with you in principle on this one. Hormonal treatment, and TRT in general, with all of the intricacies involved do not commonly lend themselves well to simplistic approaches - no matter how convenient they may be. In fact, the MAJORITY of my patients that come to me from other clinics come to me for exactly that reason... the other clinic's approach was TOO simplistic. The other provider did not have an appreciation for the "finer" aspects of TRT/HRT.

Should patients be injecting themselves multiple times unnecessarily? Of course not, but if, based on a comprehensive consultation AND thorough discussion about alternative options, it is mutually decided (between patient and provider) that a more complex (ie: more time-consuming or more demanding) regimen is ideal, then that is the regimen they should be on. If the patient is agreeable (and is empowered and educated that they have a say in the treatment) they are much MORE likely to remain compliant with ANY treatment regimen - no matter how complex it may be.

Time will tell, no doubt big pharma will do their part, but IMPO nothing replaces seeing a qualified provider who has experience and knowledge in this area and can develop a CUSTOMIZED and MODIFIABLE (because as we know things often change and require adjustments) treatment plan. Not saying it will, but if left to big pharma, convenience + simplicity will = cookie cutter, and we all should then go buy that cooking equipment because it will NOT be good for anyone!

Dr Saya

^^^^I couldn't agree more with both Drs. statements here.

I personally have a disdain for these "$199/month" clinics who run just enough labs to legally prescribe a controlled substance and whose business revenue model is built upon how many men they can get through their revolving door in absence of conducting proper medical protocols.

HRT in men is just to damn complex to conduct proper healthcare any other way and it's Drs. like Crisler and Saya and the others who "do it right" is the only responsible way in my opinion.