Trying to understand Testopel dosage

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phalloguy100

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A urologist I saw recently is recommending that I try Testopel pellets. He was saying to start with 2 x 75mg pellets every 3-4 months. If you divide that by 4 months, that's an average of 1.25mg of testosterone daily.

My last great protocol was testosterone cypionate sub-q, 3 times a week at 50mg, or 150mg per week. Since 96% of testosterone cypionate is excreted by the body, only 4% is actually absorbed. That averages to only 0.857mg of testosterone daily.

I know that 2 pellets sound like too little, but comparing the daily dosage, this would be higher than subq injections. Is this correct, or am I totally off??!!
 
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I'm not alone in considering pellets to be one of the worst forms of TRT. Mainly they are a good income source for the doctors implanting them.

An average of 1.25 mg testosterone per day is much too small. The average natural production for healthy young men is 6-7 mg/day. When you were injecting 150 mg of testosterone cypionater per week you were absorbing 15 mg of testosterone per day, which is excessive; absorption is nearly 100% and cypionate is 70% testosterone by weight.
 
I'm not alone in considering pellets to be one of the worst forms of TRT. Mainly they are a good income source for the doctors implanting them.

An average of 1.25 mg testosterone per day is much too small. The average natural production for healthy young men is 6-7 mg/day. When you were injecting 150 mg of testosterone cypionater per week you were absorbing 15 mg of testosterone per day, which is excessive; absorption is nearly 100% and cypionate is 70% testosterone by weight.

Well that's good to know! Could you give me more details - why are pellets not the greatest?


I was looking at the FDA package insert for depo-testosterone. Maybe I'm not understanding it correctly, but it sounds to me like 96% is excreted and not used by the body:

"About 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver."

"Testosterone cypionate and its metabolites are predominantly eliminated via the renal route, with approximately 90% excreted in urine as glucuronic and sulfuric acid conjugates. A smaller fraction, about 6%, is excreted in feces in its unconjugated form."
 
Well that's good to know! Could you give me more details - why are pellets not the greatest?
...
Summarized nicely by @FunkOdyssey: "I would rank pellets dead last among all possible TRT modalities. The 'locked in for months at a gradually waning dose with zero control over my experience' concept is a showstopper." They can be expensive. The implantation can be painful. You can develop scar tissue. Sometimes they escape before healing has occurred.

..
I was looking at the FDA package insert for depo-testosterone. Maybe I'm not understanding it correctly, but it sounds to me like 96% is excreted and not used by the body:
...
This has nothing to do with absorption, which is close to 100%. This is just about how the body is getting rid of it in the end. It is being used continually as it is slowly absorbed from the depot.
 
Testopel pellets
Run!

Minor surgery every time you need a new implant? No thanks.

Money grabbing, almost useless.

But I am sure the Doc appreciates the Mercedes.

For reference, a 100 pack of 29g insulin pins still under 20 bucks

tenor-3232366331.gif
 
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A urologist I saw recently is recommending that I try Testopel pellets. He was saying to start with 2 x 75mg pellets every 3-4 months. If you divide that by 4 months, that's an average of 1.25mg of testosterone daily.

My last great protocol was testosterone cypionate sub-q, 3 times a week at 50mg, or 150mg per week. Since 96% of testosterone cypionate is excreted by the body, only 4% is actually absorbed. That averages to only 0.857mg of testosterone daily.

I know that 2 pellets sound like too little, but comparing the daily dosage, this would be higher than subq injections. Is this correct, or am I totally off??!!

Way too low a dose!

More like 600-1200 mg.

Even then would not waste my time with pellets.






5 Absorption

5.1 Mechanism of absorption


Absorption of testosterone from the pellets occurs via an uniform erosion of the pellet's surface. Empirical evidence for this includes the observation that pellets recovered up to 3 months after implantation retain their cylindrical shape (Fig. 2). A mathematical model incorporating a uniform rate of surface erosion (Forbes 1941) fits data available from direct measurements of release rate well (Bishop and Folley 1951). Direct testing of the importance of pellet surface area for absorption is difficult since in the two pellet sizes available, surface area and dose are mostly confounded due to the common cylindrical shape and diameter. In order to examine for evidence of an effect of pellet surface area independent of dose, we compared the effects of 3 x 200 mg with 6 x 100 mg pellet implants which controlled for total dose (600 mg) while allowing for a 16% difference in initial surface area. The regimen with greater initial surface area produced higher free testosterone levels and greater gonadotropin suppression in the first (but not the second) 3 months. This evidence supports the surface area-limited release mechanism. Deviations from the surface erosion model can be expected if the absorbing area enlarges unpredictably due to surface irregularities, pitting or fragmentation of the pellet or if absorption via matrix-controlled diffusion supervenes as the pellet size decreases. While pellet geometry (especially surface area) appears the rate-limiting factor in testosterone absorption from subdermal pellets (Emmens 1941), additional factors are also important. These include (i) the chemistry of the steroid especially its hydrophobicity, (ii) pellet hardness, smoothness and size, (iii) the site of implantation, its local blood flow and trauma and (iv) the tissue reaction and encasing of the pellet (Foss 1939; Emmens 1941;Forbes 1941; Bishop and Folley 1951). Circulating sex steroid levels, however,appear not to be important (Emmens, 1941). Few of these factors have been systematically tested in humans and the importance of pellet geometry and site of implantation in regulating testosterone release rate warrant further evaluation.




5.2 Kinetics of absorption

Absorption rate of testosterone from pellets appears to be limited by the exposed pellet surface area from which the steroid leeches out into the extracellular fluid. Empirical calculation of the effective testosterone release rate can be made both directly from measurement of residue in extruded pellets and indirectly from the percent absorbed-time plots and these independent estimates are in reasonable agreement. A direct estimate of absorption rate of 1.5 (95% c.L. 1.4-1.7) mg/ dayl 200 mg pellet was derived from remnants of six 200 mg pellets which exhibited linear rate of release with time up to 92 days (Fig.3). An indirect, corroborative estimate was obtained independently from the percent absorbed-time plots which, being nearly linear (Fig.4), provided evidence of a very good approximation to ideal zero-order release for either total or free testosterone. These curves provided an estimate of 2.5 months for the effective half-time of absorption and calculated testosterone release rate of 0.65 mg/day/l00 mg pellet. Neither the size nor number of pellets influenced the rate of testosterone absorption. These calculations are comparable with the only other available estimate of 1.1 mg/day/l00 mg pellet from fused testosterone pellets removed at intervals after implantation in the antecubital or subscapular region (Bishop and Folley1951). The 41 % lower release rate of fused pellets implanted in the anterior abdominal wall (our study) despite a 66% greater initial surface area suggest important site-specific release characteristics.

The present estimates of testosterone release rate are also consistent with indirect estimates that can be calculated (much less accurately) from increments incirculating testosterone produced by implantation of single 100 mg and 200 mg pellets in women (Thorn et al. 1981; Dewis et al. 1986) after correcting for gender differences in testosterone clearance rates (Southren et al. 1968; Gandy 1977).





6 Bioavailability

The bioavailability of testosterone from subdermal pellets is virtually complete as calculated from the net appearance of testosterone in the bloodstream. The net release of testosterone in the circulation can be calculated from the time-course of testosterone levels if the whole body testosterone metabolic clearance rate is known and remains constant throughout the study. Since SHBG levels, which are the major determinant of testosterone metabolic clearance rate (Vermeulen et al.1969), remain unaltered following pellet implantation it is reasonable to assume a constant testosterone clearance rate (mean 540 l/sq m/day [Southren et al.1968; Gandy 1977]) throughout the life-span of a pellet implant. Such a calculation indicates that by 6 months virtually all the testosterone from the 600 mg pellet and about 90% of that in the 1200 mg pellets was absorbed. Consistent with the near complete bioavailability, net testosterone release is closely correlated with pellet dose (r=0.999) so that a 6 x 200 mg dose regimen gives twice that of either 6x 1 00 mg or 3 x 200 mg regimen, the latter two of which gave very similar net release of testosterone. This high bioavailability is not unexpected for a steroid administered parenterally and absorbed into the systemic circulation avoiding first-pass hepatic inactivation.




 
I was just talking to my doc about pellets. She was telling me that they release based on metabolic load(blood flow). So for example after a workout you’d have higher test levels. I’ve saw no where that has stayed such. Is she full of shit?
 
I was just talking to my doc about pellets. She was telling me that they release based on metabolic load(blood flow). So for example after a workout you’d have higher test levels. I’ve saw no where that has stayed such. Is she full of shit?
While superficially it is a plausible hypothesis, you could make the same argument for injections and topical testosterone. Especially with IM injections, you could suggest greater release during activity. The skin acts as a testosterone reservoir for topical testosterone. Mightn't increased blood flow speed up the transfer? In any case, it is somewhat speculative, and it's also questionable that the effect would be meaningful even if it exists.
 
While superficially it is a plausible hypothesis, you could make the same argument for injections and topical testosterone. Especially with IM injections, you could suggest greater release during activity. The skin acts as a testosterone reservoir for topical testosterone. Mightn't increased blood flow speed up the transfer? In any case, it is somewhat speculative, and it's also questionable that the effect would be meaningful even if it exists.
I’ll likely have a discussion about this with her. She’s very open minded and up for discussion but I’ve yet to outright question her before.
 
While superficially it is a plausible hypothesis, you could make the same argument for injections and topical testosterone. Especially with IM injections, you could suggest greater release during activity. The skin acts as a testosterone reservoir for topical testosterone. Mightn't increased blood flow speed up the transfer? In any case, it is somewhat speculative, and it's also questionable that the effect would be meaningful even if it exists.
Amen.

Nice marketing.
 
@Cataceous this is what chatgpt had to say about how much testosterone cypionate is excreted unused:

“The exact percentage of excreted testosterone after an injection of testosterone cypionate can vary depending on factors such as an individual’s metabolism, liver function, and the dose administered. However, to give a general idea:

- **Metabolism and Excretion:** After injection, testosterone is gradually released into the bloodstream, where it undergoes metabolism primarily in the liver. The liver converts testosterone into inactive metabolites, such as androsterone and etiocholanolone, which are then excreted through the kidneys into the urine.

- **Percentage Excreted:** Roughly 90-95% of administered testosterone is metabolized and excreted, primarily in the urine, within a few days to weeks after injection. The remaining percentage is used by the body for physiological processes, including the maintenance of male characteristics, muscle mass, bone density, and libido.

- **Biological Availability:** The amount of testosterone that remains available for physiological functions after the first-pass metabolism (which primarily occurs in the liver) is considered biologically active testosterone. This is generally the small fraction that is not tightly bound to proteins like SHBG or metabolized into other forms.

So, while a significant percentage of the administered testosterone is excreted after being metabolized, the fraction that remains active in the bloodstream for use by tissues is what exerts the desired therapeutic effects.”

So if 90%-95% is metabolized and excreted, then I think my math might be right??

I asked the urologist about it and he just said that pellets work completely different than injections, and that 2 pellets are conservative but he would want to start slow to see how I respond.
 
@Cataceous this is what chatgpt had to say about how much testosterone cypionate is excreted unused:

“The exact percentage of excreted testosterone after an injection of testosterone cypionate can vary depending on factors such as an individual’s metabolism, liver function, and the dose administered. However, to give a general idea:

- **Metabolism and Excretion:** After injection, testosterone is gradually released into the bloodstream, where it undergoes metabolism primarily in the liver. The liver converts testosterone into inactive metabolites, such as androsterone and etiocholanolone, which are then excreted through the kidneys into the urine.

- **Percentage Excreted:** Roughly 90-95% of administered testosterone is metabolized and excreted, primarily in the urine, within a few days to weeks after injection. The remaining percentage is used by the body for physiological processes, including the maintenance of male characteristics, muscle mass, bone density, and libido.

- **Biological Availability:** The amount of testosterone that remains available for physiological functions after the first-pass metabolism (which primarily occurs in the liver) is considered biologically active testosterone. This is generally the small fraction that is not tightly bound to proteins like SHBG or metabolized into other forms.

So, while a significant percentage of the administered testosterone is excreted after being metabolized, the fraction that remains active in the bloodstream for use by tissues is what exerts the desired therapeutic effects.”

So if 90%-95% is metabolized and excreted, then I think my math might be right??

No.

I asked the urologist about it and he just said that pellets work completely different than injections, and that 2 pellets are conservative but he would want to start slow to see how I respond.

Hand waving by your urologist. Whether you inject, place a pellet, snort it, whatever, your body is going to process the free exogenous test the exact same way once it hits your blood stream. Hence the gross amount of test delivered per day has to be the same no matter the delivery method assuming bioavailabilty 100% in order to achieve the same mean daily serum concentration. Your body doesn't know it is getting test from an implanted pellet.

See "Metabolism" section.


Did you not read all the words @madman shared with you? I really do understand why he is so pissy most of the time.

Your urologist is basically selling you homeopathic TRT. Completely bonkers.

What a racket. What is the charge for this "service"? What would you be paying per year?
 
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I was just talking to my doc about pellets. She was telling me that they release based on metabolic load(blood flow). So for example after a workout you’d have higher test levels. I’ve saw no where that has stayed such. Is she full of shit?

Maybe hop on one of these for a little extra boost on your absorption rate constant?


tumblr_n90ywpApXB1qzxeqqo2_r1_500.gif
 
No.



Hand waving by your urologist. Whether you inject, place a pellet, snort it, whatever, your body is going to process the free exogenous test the exact same way once it hits your blood stream. Hence the gross amount of test delivered per day has to be the same no matter the delivery method assuming bioavailabilty 100% in order to achieve the same mean daily serum concentration. Your body doesn't know it is getting test from an implanted pellet.

See "Metabolism" section.


Did you not read all the words @madman shared with you? I really do understand why he is so pissy most of the time.

Your urologist is basically selling you homeopathic TRT. Completely bonkers.

What a racket. What is the charge for this "service"? What would you be paying per year?
Thanks man. And yes I did see those links but there was nothing to support what you are saying with data (unless I missed it).

This link you provided, under figure 2, support what my urologist and chatgpt are saying. It shows that of the 5-8mg T produced daily on non-hypogonadonal men, 5.2% is used and the rest is wasted by the liver. So 0.26-0.416mg daily are all the body uses… which is in line with the depo-test insert and the Testopel studies showing a 0.6-ish mg/day release per pellet.


Well anyway, I am thankful for everyone’s feedback here. I will do more research on pubmed before deciding whether to try pellets or not.
 
Thanks man. And yes I did see those links but there was nothing to support what you are saying with data (unless I missed it).

This link you provided, under figure 2, support what my urologist and chatgpt are saying. It shows that of the 5-8mg T produced daily on non-hypogonadonal men, 5.2% is used and the rest is wasted by the liver. So 0.26-0.416mg daily are all the body uses… which is in line with the depo-test insert and the Testopel studies showing a 0.6-ish mg/day release per pellet.


Well anyway, I am thankful for everyone’s feedback here. I will do more research on pubmed before deciding whether to try pellets or not.
If all the body uses is 0.3 mg/day and 95% is "wasted" (rough numbers), how much free testosterone does the pellet need to release per day?

0.3 ÷ 0.05 = 7 mg/day (required supply of exogenous free T via implanted pellet)

Or for Test Cyp:

7 mg/day T ÷ 0.7 = 10 mg/day (70 mg/week) of Test Cyp

Compare with what madman shared above.

If testopel is releasing 0.6 mg/day, then what does that leave you with after accounting for the 95% inactivated?

Somebody is coming up short by an order of magnitude.

Hope you are doing well @madman
 
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A high degree of redundancy exists in the hepatic biotransformation of endogenous ligands such as testosterone. Testosterone is susceptible to hydroxylation by multiple P450 enzymes, oxidoreduction to androstenedione and androstanediols, and conjugation to either glucuronic acid or sulfate. All of these metabolic conversions contribute to the inactivation of the hormone. The present study demonstrated that the inhibition of certain biotransformation enzymes did not significantly impact changes in serum testosterone levels. The redundancy in biotransformation processes may be responsible for ensuring that endogenous ligands such as testosterone are efficiently cleared despite the selective inhibition of some biotransformation enzymes.

In conclusion, the results from this study indicate that testosterone levels are controlled primarily by the rate of synthesis. Chemically induced effects on hepatic steroid hormone biotransformation processes do not necessarily imply altered steroid hormone homeostasis. As noted in the introduction, there are many instances in the scientific literature where xenobiotic-mediated changes in the rate of steroid hormone biotransformation and inactivation are presumed to lead to alterations in circulating hormone levels. Our results indicate that this assertion should not be made without careful investigation.
 

Order of reaction...

For almost all drugs, the metabolism rate in any given pathway has an upper limit (capacity limitation). However, at therapeutic concentrations of most drugs, usually only a small fraction of the metabolizing enzyme’s sites are occupied, and the metabolism rate increases with drug concentration. In such cases, called first-order elimination (or kinetics), the metabolism rate of the drug is a constant fraction of the drug remaining in the body (ie, the drug has a specific half-life).

For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 hour and 125 mg at 2 hours (illustrating a half-life of 1 hour). However, when most of the enzyme sites are occupied, metabolism occurs at its maximal rate and does not change in proportion to drug concentration; instead, a fixed amount of drug is metabolized per unit time (zero-order kinetics). In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 hour and 400 mg at 2 hours (illustrating a maximal clearance of 50 mg/hour and no specific half-life). As drug concentration increases, metabolism shifts from first-order to zero-order kinetics.

Assuming inactivation is first order, what can we conclude in our above example? Will the ~95% inactivation assumption hold for release rates of 5 mg/day and 0.5 mg/day?

Surely inactivation percentage won't decrease as release rate decreases from 5 down to 0.5 mg/day. Hope this helps.

Feel free to come slap me @RickB
 
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@Cataceous this is what chatgpt had to say about how much testosterone cypionate is excreted unused:
...
You didn't get an answer to the question. Maybe you phrased it differently? When I asked it refused to give a percentage.

Instead of a percentage, here’s a more nuanced understanding:
  • Incomplete Utilization: It’s safe to say that some percentage of injected testosterone cypionate will be excreted unused.
In actuality, this is a very small amount, a fact determined by various studies. Most of the testosterone cypionate is able to release its testosterone shortly after entering the bloodstream. Wikipedia refers to IM bioavailability as "very high". I found a more productive query for ChatGPT:

Here’s a breakdown of what happens to testosterone after it’s used for a function like binding to the androgen receptor:
1. Binding and Dissociation:
  • Binding: Testosterone binds to the androgen receptor, triggering a cascade of events leading to gene expression and cellular changes. This binding is reversible, meaning the testosterone molecule can detach from the receptor.
  • Dissociation: After a period of time, testosterone will naturally dissociate from the androgen receptor. This is influenced by factors like the concentration of testosterone in the cell, the binding affinity of the testosterone to the receptor, and the presence of other molecules that compete for binding.
2. Metabolic Fate:
Once testosterone dissociates from the receptor, it undergoes a series of metabolic transformations. Here’s the general breakdown:
  • 5α-Reductase: An enzyme called 5α-reductase converts testosterone into dihydrotestosterone (DHT). DHT is a more potent androgen and can bind to the androgen receptor with higher affinity. This pathway is important for some androgen-dependent functions, like prostate growth.
  • Aromatase: Another enzyme called aromatase converts testosterone into estradiol, a form of estrogen. This pathway is essential for maintaining a balance of sex hormones.
  • Hydroxylation: Testosterone can also undergo hydroxylation (addition of a hydroxyl group) by enzymes like CYP3A4. This leads to the formation of metabolites like androsterone and etiocholanolone, which are less active and more readily excreted.
  • Glucuronidation and Sulfation: These processes involve attaching sugar or sulfate molecules to testosterone, making it more water-soluble and facilitating its excretion in urine or bile.
Although it's a simplification, the key point here is that the testosterone directly doing the useful things is just borrowed from the free testosterone passing by. The higher the concentration, the more that gets done. But the process is nondestructive. I like a fluid flow analogy: Testosterone is constantly flowing from the point of production or absorption to the end result of metabolism and elimination. This process is relatively independent of the useful functions that occur along the way, which temporarily borrow some fraction of the testosterone passing by.

Ignoring some other conversions, estradiol and DHT metabolites generally follow the same paradigm after they are created from free testosterone: While flowing to their eventual metabolism and elimination they are borrowed for some useful functions.

An additional point is that the testosterone molecules that don't do anything before being metabolized and excreted should not be considered as wasted. Rather, they are contributing to the concentration of testosterone such that the desired interactions can occur. If you didn't have those "wasted" T molecules then it would be like cutting your free testosterone to a few percent of normal, which would have unpleasant consequences.
 
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