Pharmacokinetic Evaluation and Dosing of Subcutaneous Testosterone Pellets

[Michael Scally MD]

Subcutaneous T pellet implants have been available in the United States since 1972 and afford several advantages over other T formulations, including 100% patient compliance, avoidance of the peaks and troughs found with injectable treatments, lower risk of drug transfer from patient to others, and maintenance of a stably elevated serum T level. While T pellets are used to treat androgen deficiency, limited data exist regarding their pharmacokinetics and side effect profiles. Furthermore, the incidence of erythrocytosis and effects on lipid profiles is relatively unknown for T pellets.

Determining optimal dosing of T pellets can be challenging, as individual rates of T metabolism must be considered, and these likely reflect patient weight and body mass index (BMI), as well as volume of distribution and sex hormone binding globulin (SHBG) concentration. Thus, further evaluation of the pharmacokinetics of T pellets is merited in order to determine optimal dosing and to establish side effect profiles. In this study, researchers evaluate the pharmacokinetics of T pellets in a cohort of hypogonadal men, permitting an objective evaluation of serum T metabolism and leading to dosing parameters for these pellets. They also assess symptomatic benefits of T pellets as well as adverse events including erythrocytosis and impact on PSA levels.

They find that subcutaneous T pellets represent a safe, efficacious mode of TRT, and that the effects on serum hormone levels and hypogonadal symptoms of these pellets are a function of the number of pellets implanted and patient BMI. Men with BMI <25 achieve therapeutic TT levels with fewer than 10 pellets, whereas men with BMI ?25 require 10 or more pellets to achieve therapeutic TT levels, and most men demonstrate improvement in hypogonadal symptoms after pellet implantation. Regardless of the number of pellets implanted, roughly equal serum TT levels are observed at 100-120 days, indicating that re-implantation should be performed at this time. Furthermore, 320 multiple sequential implantations do not appear to affect TT decay kinetics, nor do pre-implantation TT levels. Finally, minimal effects on Hgb and Hct parameters, and no effects on PSA, particularly in men with CaP, were observed.

Pastuszak AW, Mittakanti H, Liu JS, Gomez LP, Lipshultz LI, Khera M. Pharmacokinetic Evaluation and Dosing of Subcutaneous Testosterone Pellets. J Androl. Pharmacokinetic Evaluation and Dosing of Subcutaneous Testosterone Pellets -- Pastuszak et al., 10.2164/jandrol.111.016295 -- Journal of Andrology

Introduction and Objective: Subcutaneous testosterone (T) pellets are a viable treatment modality for hypogonadism. Optimal dosing, frequency of reimplantation, and long-term safety of T pellets remain incompletely elucidated parameters.

Methods: A retrospective review of 273 patients treated for hypogonadism using subcutaneous T pellets was performed. Serum total T (TT), free T (FT), and estradiol (E) levels were analyzed as a function of time from implantation, number of pellets implanted (6-9 or 10-12), BMI (<25 or >/=25), number of implantations (up to 4 rounds, 501 insertions) and pre-implantation T levels (<300 or >/=300ng/dL). T decay was determined using linear regression and TT levels at day 1 post-implantation and the time for TT levels to reach 300ng/dL extrapolated for all variables.

Results: Mean(SD) subject age was 56±12.6 years. Baseline TT was 328±202 ng/dL, FT 9.49±27.8 pg/mL and E 25.1±17.3 pg/mL. Extrapolated TT and FT peaks were lower in men receiving 6-9 pellets than 10-12, though decay rates differed insignificantly. E levels rose significantly in men receiving 10-12, but not 6-9 pellets. Men with BMI >/=25 attained lower TT peaks with slower decay than men with BMI <25 receiving 10-12 pellets, though 300ng/dL TT levels were reached at ~100 days in both groups. No differences were seen in decay rates for men with multiple implant rounds, and no differences in T peaks or decay rates were seen in men with pre-implant T <300 or >/=300ng/dL. One patient developed erythrocytosis and no PSA recurrences were observed in men with prostate cancer treated with T pellets.

Conclusions: Men with BMI <25 should receive fewer pellets and re-implantation for all men should occur 100-120 days after prior implantation. Men receiving 10-12 pellets have higher E levels, potentially reflecting increased aromatization of testosterone. Reimplantation and pre-implantation TT levels do not affect pellet decay kinetics.

 

[cvictorg]

While T pellets are used to treat androgen deficiency, limited data exist regarding their pharmacokinetics and side effect profiles. Furthermore, the incidence of erythrocytosis and effects on lipid profiles is relatively unknown for T pellets.

Determining optimal dosing of T pellets can be challenging, as individual rates of T metabolism must be considered, and these likely reflect patient weight and body mass index (BMI), as well as volume of distribution and sex hormone binding globulin (SHBG) concentration. Thus, further evaluation of the pharmacokinetics of T pellets is merited in order to determine optimal dosing and to establish side effect profiles.

They find that subcutaneous T pellets represent a safe, efficacious mode of TRT, and that the effects on serum hormone levels and hypogonadal symptoms of these pellets are a function of the number of pellets implanted and patient BMI. Men with BMI <25 achieve therapeutic TT levels with fewer than 10 pellets, whereas men with BMI ?25 require 10 or more pellets to achieve therapeutic TT levels, and most men demonstrate improvement in hypogonadal symptoms after pellet implantation. Regardless of the number of pellets implanted, roughly equal serum TT levels are observed at 100-120 days, indicating that re-implantation should be performed at this time.

How many men want to undergo a surgical procedure every 3-4 months??

"Men with BMI <25 achieve therapeutic TT levels with fewer than 10 pellets, whereas men with BMI ?25 require 10 or more pellets to achieve therapeutic TT levels." Not quite specific enough for my taste.

At least with cream or injections blood work can be done and the dosage can be adjusted immediately.

I do not think anyone should have pellets as a form of TRT/HRT - IMHO - and I've undergone pellet therapy so I can speak from experience

 

[LW64]

How many men want to undergo a surgical procedure every 3-4 months??

"Men with BMI <25 achieve therapeutic TT levels with fewer than 10 pellets, whereas men with BMI ?25 require 10 or more pellets to achieve therapeutic TT levels." Not quite specific enough for my taste.

At least with cream or injections blood work can be done and the dosage can be adjusted immediately.

I do not think anyone should have pellets as a form of TRT/HRT - IMHO - and I've undergone pellet therapy so I can speak from experience

It certainly would not be the first method I'd want to try.

 

[BBC3]

All the article says was FATBOYS dont need a whole lot of extra E fuel on board or bad newzzz.....

I have never had pellets but know a few and they did not really complain. To call it "surgical" is really speculative. The truth is a 21 ga. pin causes an "INCISION". an not a "HOLE". So where is the line??

I find it funny that all these delivery methods and so futile to achieve the goal of TRT when T pellet is the LOGICAL OPTIMAL CHOICE. It is really INSANITY and further proof that TRT is not what the subject needed in the first place anyway.

The only optimal solution other than pellets I speculate would be PATCHES. Period. STEADY DELIVERY .... IS THE KEY.....

I almost see patches as a better solution to pellet unless they have designed pellets in a way that the smaller they get - the faster they absorb. Cuase otherwise you wind up with a condition that has one dosed up too high for a month or two and then dwendling. IF YOU NOTE the end of the article summary, the addtiion of more pellets DOES NOT change the DECAY RATE. This statement MUST be an obvious admission of the factual design of the pellets ( so essentially you are MAX'D at the second dosing inception), and they must be citing data from serum counts. Else I dont know how they could come up with that other than as horse shit.

It is a matter of design/intent as it relates to exogenous application with regard to endogenous supply/demand principle. With pellets, you are going to be looking at more of a "force feeding" scenario, as they trickle into ciculating supply. Its not excess that hurts so much, its what your body can POTENTIALLY do with the excess - and depending on you given conditions - fat levels.

Again to anyone technical reading. You should denote the cited alarm over high body fat individuals rather than high muscle. Clearly fat is inteacting with Es much more slowly than muscle involves with A's. The relationship again is clear as there is usually a pretty static metabolism with regard to FAT. If hormones indeed service TISSUE ACTIVITY, then go figure. So funny, once we are fat, it takes so little to become a negative... And here we are endeavoring to FEED THE ADIPOSE BEAST when all along so easily satisfied. TRT soon to equate Testosterone Redundancy THEORY....[)]

In the end the question will boil down to RELATIVE PROPORTION vs. GENERAL AVAILABILITY. Whether its more ok to have excess estrogens as long as there are androgens to conbat, OR is there no complimentary/protective relationship at all, and we are simply SMOKING OUR PROSTATES.....!?

How many men want to undergo a surgical procedure every 3-4 months??

"Men with BMI <25 achieve therapeutic TT levels with fewer than 10 pellets, whereas men with BMI ?25 require 10 or more pellets to achieve therapeutic TT levels." Not quite specific enough for my taste.

At least with cream or injections blood work can be done and the dosage can be adjusted immediately.

I do not think anyone should have pellets as a form of TRT/HRT - IMHO - and I've undergone pellet therapy so I can speak from experience

 

[jonkobeck]

How many men want to undergo a surgical procedure every 3-4 months??

Cmon Man

"Surgical procedure" ??? Are you serious?
I have had pellets done and will be repeating them in 2 weeks. This is NOT a surgical procedure, lol No offense, but I think your being overly dramatic.
In fact, it takes 5 minutes. the pellets are "injected" with a syringe type tool, they are the size of a grain of rice. No cutting, no bleeding (for me anyway) no stitches. In and out in 15 minutes, see you in 4 months

My T level was a stable 950 on pellets, something I could never get on gels.

And in my opinion ,its much more viable then harpooning myself with a needle every few days. No peaks and valleys with pellets either. My insurance (Aetna) covers it too.[

 

[jonkobeck]

All the article says was FATBOYS dont need a whole lot of extra E fuel on board or bad newzzz.....

I have never had pellets but know a few and they did not really complain. To call it "surgical" is really speculative. The truth is a 21 ga. pin causes an "INCISION". an not a "HOLE". So where is the line??

I find it funny that all these delivery methods and so futile to achieve the goal of TRT when T pellet is the LOGICAL OPTIMAL CHOICE. It is really INSANITY and further proof that TRT is not what the subject needed in the first place anyway.

The only optimal solution other than pellets I speculate would be PATCHES. Period. STEADY DELIVERY .... IS THE KEY.....

I almost see patches as a better solution to pellet unless they have designed pellets in a way that the smaller they get - the faster they absorb. Cuase otherwise you wind up with a condition that has one dosed up too high for a month or two and then dwendling. IF YOU NOTE the end of the article summary, the addtiion of more pellets DOES NOT change the DECAY RATE. This statement MUST be an obvious admission of the factual design of the pellets ( so essentially you are MAX'D at the second dosing inception), and they must be citing data from serum counts. Else I dont know how they could come up with that other than as horse shit.

It is a matter of design/intent as it relates to exogenous application with regard to endogenous supply/demand principle. With pellets, you are going to be looking at more of a "force feeding" scenario, as they trickle into ciculating supply. Its not excess that hurts so much, its what your body can POTENTIALLY do with the excess - and depending on you given conditions - fat levels.

Again to anyone technical reading. You should denote the cited alarm over high body fat individuals rather than high muscle. Clearly fat is inteacting with Es much more slowly than muscle involves with A's. The relationship again is clear as there is usually a pretty static metabolism with regard to FAT. If hormones indeed service TISSUE ACTIVITY, then go figure. So funny, once we are fat, it takes so little to become a negative... And here we are endeavoring to FEED THE ADIPOSE BEAST when all along so easily satisfied. TRT soon to equate Testosterone Redundancy THEORY....[)]

In the end the question will boil down to RELATIVE PROPORTION vs. GENERAL AVAILABILITY. Whether its more ok to have excess estrogens as long as there are androgens to conbat, OR is there no complimentary/protective relationship at all, and we are simply SMOKING OUR PROSTATES.....!?

My E2 on gels shot up to 95.
On Pellets it went to 65, still not great, but better then gels. I may try A-Dex, depending on what my levels are on this next draw.
Oh, and I m a "fat boy'

 

[vantage108]

My T level was a stable 950 on pellets, something I could never get on gels.

A stable 950 with no fuss for four months sounds excellent. I don't think my doctor does these, but I'm curious enough now to ask.

 

[BBC3]

Man - All the bold on the above dude...?!? Peace to ya...

I still want to reitterate that I recalled you stating 12 pellets per side I thought!?!?!?! I would seriously inquire as to cutting that dose in half if I recall correctly. I may be wrong on my memory though..

Point here is I want to emphasize that even though the E2 was lower with pellets, the damage may be the same. You will have to buy into my Serum Count Issues to get that one.

But reinstating the point that the failure of gels is the INFUX. And multipronged as the SPIKE is creating an encouraging enviroment for excess hormone availability to wreak havok. While Shippen is big on, or got his start emphasizing Circadian Rythym, I think he has it completely backward in that Surges in Serum Count are representative of Demand Fluctuation and not SUPPLY. The supply MUST remain constant - at least the constant MIN one is willing to accept based on their own physical attributes. EXCESS is never good and only WORTHLESS if not detrimental in short burst, biological CHOAS inducing at best.... I suspect that if you were to compare the LACK of efficacy of a FAILED Depot Injection/Poor injection regimen Protocol, to a Cream or Gel - it would be a toss up.... LOL[)]

Well, I guess he BOLDED ya pretty good - LOL////

My E2 on gels shot up to 95.
On Pellets it went to 65, still not great, but better then gels. I may try A-Dex, depending on what my levels are on this next draw.
Oh, and I m a "fat boy'

 

[jonkobeck]

Man - All the bold on the above dude...?!? Peace to ya...

I still want to reitterate that I recalled you stating 12 pellets per side I thought!?!?!?! I would seriously inquire as to cutting that dose in half if I recall correctly. I may be wrong on my memory though..

Point here is I want to emphasize that even though the E2 was lower with pellets, the damage may be the same. You will have to buy into my Serum Count Issues to get that one.

But reinstating the point that the failure of gels is the INFUX. And multipronged as the SPIKE is creating an encouraging enviroment for excess hormone availability to wreak havok. While Shippen is big on, or got his start emphasizing Circadian Rythym, I think he has it completely backward in that Surges in Serum Count are representative of Demand Fluctuation and not SUPPLY. The supply MUST remain constant - at least the constant MIN one is willing to accept based on their own physical attributes. EXCESS is never good and only WORTHLESS if not detrimental in short burst, biological CHOAS inducing at best.... I suspect that if you were to compare the LACK of efficacy of a FAILED Depot Injection/Poor injection regimen Protocol, to a Cream or Gel - it would be a toss up.... LOL[)]

Well, I guess he BOLDED ya pretty good - LOL////

Yes 12 pellets gave me 950 4 weeks into therapy.
Im still debating if 950 is too high.
I will ask the doc, maybe try 10.

 

[hypohypophysis]

Ok, I'm sure there are a hundred threads on this subject, but since this is on here maybe there are more current opinions? Which method do ya'll prefer and why? I currently am on Androgel. I have used Testim, patches and cypionate with various injection frequencies. Most doctors seem to want to use the creams, which they justify as being more stable (less peaks and troughs). I don't like the creams, I like weekly cypionate injections due to frequent bathing, sweating and the pain in the ass factor of having to do it every day. Patches don't stay on; however, I will say that I noticed an improved erectile response over the other methods when I could keep them on. Are the pellets worth it? What are you're experiences with it? It would be nice to just have it done and be done with it, but its kind of hard to adjust your dose accordingly I'm guessing.

 

[jonkobeck]

Ok, I'm sure there are a hundred threads on this subject, but since this is on here maybe there are more current opinions? Which method do ya'll prefer and why? I currently am on Androgel. I have used Testim, patches and cypionate with various injection frequencies. Most doctors seem to want to use the creams, which they justify as being more stable (less peaks and troughs). I don't like the creams, I like weekly cypionate injections due to frequent bathing, sweating and the pain in the ass factor of having to do it every day. Patches don't stay on; however, I will say that I noticed an improved erectile response over the other methods when I could keep them on. Are the pellets worth it? What are you're experiences with it? It would be nice to just have it done and be done with it, but its kind of hard to adjust your dose accordingly I'm guessing.

From my standpoint, YES the pellets are worth it. BUT don't expect a positive response from others. I frequent a few of these steroid type forums, and not many people are positive about them, UNTIL they try them. I think a lot of this is psychological. Many guys on here are weight lifters and pump a lot of iron, there is some macho connotation about harpooning themselves with a needle every week. Another problem is that not many folks insurance will cover it, and if you don't have insurance its not cheap, I have insurance and pay nothing.

Remember, pellets have been around for over 50 years! The reason doctors push gels imo is because its the easiest thing on their end, they write a script and thats it. Perhaps they don't want to deal with the issues of needles and educating the patient on usage etc.
I got the best response from pellets were gels didn't work. Overall, most men who actually try the pellets are pleased with the results. Most of the ones complaining about them are unwilling to try them.

 

[Millard]

From my standpoint, YES the pellets are worth it. BUT don't expect a positive response from others. I frequent a few of these steroid type forums, and not many people are positive about them, UNTIL they try them. I think a lot of this is psychological. Many guys on here are weight lifters and pump a lot of iron, there is some macho connotation about harpooning themselves with a needle every week.

There are positives and negatives associated with each of the steroid delivery methods e.g. injectable, oral, transdermal, pellets.

People have their preferences. No need to disparage groups of people who disagree with you.

As far as pellets are concerned, it seems that the surgical procedure used to implant the pellets would be considered more "macho" that a thin little needle. That's pretty hardcore lol

I agree that patients are frequently only presented with limited choices by their doctors and this is often due to financial interests pushing those options.

 

[Tyler81]

Ok, I'm sure there are a hundred threads on this subject, but since this is on here maybe there are more current opinions? Which method do ya'll prefer and why? I currently am on Androgel. I have used Testim, patches and cypionate with various injection frequencies. Most doctors seem to want to use the creams, which they justify as being more stable (less peaks and troughs). I don't like the creams, I like weekly cypionate injections due to frequent bathing, sweating and the pain in the ass factor of having to do it every day. Patches don't stay on; however, I will say that I noticed an improved erectile response over the other methods when I could keep them on. Are the pellets worth it? What are you're experiences with it? It would be nice to just have it done and be done with it, but its kind of hard to adjust your dose accordingly I'm guessing.

I've tried every option except for pellets.

Started with a cream, then patch, then injection, then gel.

For me, the gel is the most convienent for me and estrogen isn't an issue (like with shots). I also feel more "in control" with the gel because they come in the exact dose tubes so I can't really fuck around with the dose (unlike creams which r sorta hit and miss).

Pellets could be good in that sense, in that a patient can't fuck around with their dose!

Gel is ok, if i can find some consistency i will be on it for the long haul.

 

[jonkobeck]

There are positives and negatives associated with each of the steroid delivery methods e.g. injectable, oral, transdermal, pellets.
. No need to disparage groups of people who disagree with you.

As far as pellets are concerned, it seems that the surgical procedure used to implant the pellets would be considered more "macho" that a thin little needle. That's pretty hardcore lol

Not meaning to sound "disparaging" , but the mere mention of pellets seems to make people on message forums go into a pseudo-roid rage. I think the problem is people are conditioned to think that its a "surgical procedure" - when in fact it is not. Giving blood is way more uncomfortable for me then a 5 minute pellet injection. And thats exactly what it is, an injection with large needle into the fat of the buttocks.
If one has never tried it, than the reality is one can't possible comment with any intelligence as to its efficacy. But like I said, and as the good doctor pointed out, they have been around for 40 plus years

 

[Millard]

If one has never tried it, than the reality is one can't possible comment with any intelligence as to its efficacy. But like I said, and as the good doctor pointed out, they have been around for 40 plus years

LIke you said, there is several decades of data on pellet implantation. I don't think everyone must try it to determine if it's the best option for them. The data can be their guide. There are certain well-documented drawbacks to pellet implantation i.e. pellet extrusion that may make it less than ideal for athletes or anyone else who is involved in extreme physical activity and/or contact sports. I'm just saying the reason why the weightlifters you refer to who dislike pellets may be due to more practical concerns than psychological reasons or a desire to be "macho".

 

[hypohypophysis]

@tyler81 Well, I'm definitely in it for the long haul as well. I don't cycle and I'm going to take T for everyday for the rest of my life. I just want to find the most reliable, effective regimen that most closely mimics the circadian rhythms and all that. It's frustrating, cuz I've seen many doctors, and they all say something different. Also, my estrogen is high, and I've heard bad things about arimidex when it comes to joints and I already have arthritis. I'm thinking that the way to keep e2 down maybe is by using the method which produces the least amount of aromatization instead of taking a serm or AI. Although, I'd take a drug if it's safe and doesn't mess with my joints. I'd like to take hcg to maintain my testicle size and function, too, but so far no doc would write me for any script besides T. I'm sure it varies for each individual, but I just wan't the optimal level and ratio for my age while maintaining my fertility and appearance. Surely there must be a good thread on here that is concise and definitive on this issue.

 

[jonkobeck]

Even on pellets my E2 is high (62) but its lower then it was on gels.
Tomorrow I get my blood draw so we will see where I'm at now 3 months after insertion. Im starting to feel like I'm crashing though. All of a sudden no energy, live in the last few days.

 

[BBC3]

What I am unclear on is that I though you said 12 per side was what they gave you....?

I am also curious. How many milligrams of T is one pellet?

Yes 12 pellets gave me 950 4 weeks into therapy.
Im still debating if 950 is too high.
I will ask the doc, maybe try 10.

 

[jonkobeck]

What I am unclear on is that I though you said 12 per side was what they gave you....?

I am also curious. How many milligrams of T is one pellet?

Good God NO! 12 per side would be way too much. 12 pellets in one shot is what I got.
Testopel is 75mg of testosterone per pellet

 

[BBC3]

I would also like to point out that when YOUR DOC is considering what method of treatment to apply, UNFORTUNATELY, he has financial considerations.

It should be noted that first I think the "pellet docs" have been pretty much stimatized as Cattle docs by now due to $$$.. I think the proceedure costs about 600$ give or take and most insurance does not cover.

You will also find that PATCHES which are optimal IMO, and short of proper CYP IM application perhaps, are pretty damn expensive too. I believe I was quoted about 300$ for patches. Strangely my insurance ONLY wants to pay for CYP now. Perhaps Cause I have been on it. I THINK they will cover gels which may be more like 150 (not sure), but they refused the patches when I wanted to try..!>?!>!! 100 vs 300$ - Go figure.

It should also be noted that I have seen something going on as of late with the major Pharm vendors (CVS, Walgreens, etc).. They have been pulling some shit about not having basic Sandoz and Watson Generics. At first they tried to force a "Brand" on me, which I think was Schreng. I did not know they were the ORIGINAL!?!?! I always assumed Upjon T DEPOT was. I PROABABLY Have all that ackwarB.. But the long and short is APPARENTLY CVS AND WALGREENS ARE TIRED OF YOU MAKING AWAY FOR 10 WEEKS FOR 10 BUCKS, SO NOW THEY ARE PUSHING 1ML LOADS AND ONLY PROVIDING 5 WEEKS FOR THE SAME PRICE....?!? I actually brough it to the attention of BC/BS and got the push off. I assumed that they were now too getting DOUBLE CHARGED, but reflecting at this moment I suspect they are only now eating $50.00 per co-pay. AND I know many who have been getting the 10ml for min copay for a while now so will be interesting to see. I will also inquire as to what my ins is bring charged now for the half size supply.....