Peak & Trough levels for TRT

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Justy

New Member
Hi and Happy New Year ......

I'm injecting Xyosted once per week ( Friday morning, 100 mg).

I'm interested in know my Peak & Trough levels. I understand that for the Trough level I need to get the bloodwork just before I apply the Xyosted....

But I'm not sure how long after I apply Xyosted I need to get the bloodwork for Peak level...

Thx
 
Defy Medical TRT clinic doctor

madman

Super Moderator
Hi and Happy New Year ......

I'm injecting Xyosted once per week ( Friday morning, 100 mg).

I'm interested in know my Peak & Trough levels. I understand that for the Trough level I need to get the bloodwork just before I apply the Xyosted....

But I'm not sure how long after I apply Xyosted I need to get the bloodwork for Peak level...

Thx

Happy New Year!

When using exogenous esterified T whether cypionate or Xyosted (enanthate):

Injecting larger doses of T less frequently will result in driving up your TT/FT/e2 levels
and keep in mind that this initial burst release will have T levels rising within the first 2 hrs reaching peak (supra-physiological) levels 8-12 hrs post-injection and remain elevated during the first few days only to end up much lower come weeks end (trough).

Mind you when injecting strictly sub-q although there will still be a difference in the peak--->trough it may not be as extreme and levels may be more stable throughout the week.

The only way to truly know is to test at the true peak and the true trough.
 

madman

Super Moderator
Strictly IM



CONCLUSIONS: In our population of patients on stable IM T dose, there was a wide mean variation in both Tp (23%) and Tt (17.5%). In addition to that, 25% of patients had a maximum Tp change greater than 50% and maximum Tt change greater than 35%. Clinicians should be aware of this high variability in levels when deciding on dose adjustment.




 

Cataceous

Super Moderator
...
But I'm not sure how long after I apply Xyosted I need to get the bloodwork for Peak level...
...
Indeed, it looks like either ~8-12 hours post-injection for the first peak or ~36 hours post-injection for the second peak.
Image 1-2-21 at 7.05 PM.jpg

 

madman

Super Moderator
Happy New Year!

When using exogenous esterified T whether cypionate or Xyosted (enanthate):

Injecting larger doses of T less frequently will result in driving up your TT/FT/e2 levels
and keep in mind that this initial burst release will have T levels rising within the first 2 hrs reaching peak (supra-physiological) levels 8-12 hrs post-injection and remain elevated during the first few days only to end up much lower come weeks end (trough).

Mind you when injecting strictly sub-q although there will still be a difference in the peak--->trough it may not be as extreme and levels may be more stable throughout the week.

The only way to truly know is to test at the true peak and the true trough.



Look over the Cavg/Cmax/Cmin (ng/dL) and Tmax (h)

Let alone the fluctuation (peak-to-trough) ratios (overall/various doses 50/75/100 mg)
Screenshot (3150).png

Cavg 0–168h, average concentration over the 7-day dosing interval (0–168 hours); Cmax, maximum (peak) blood concentration; Cmin, minimum blood concentration; PK, pharmacokinetic; Tmax, time to reach maximum blood concentration; TT, total testosterone.

*The fluctuation (peak-to-trough) ratios were 1.813 for the overall study population and 1.854, 1.758, and 2.025 for the 50-, 75-, and 100-mg dose groups, respectively.





















 
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madman

Super Moderator
This is the first study done in Canada using subcutaneous testosterone injections let alone with a fixed insulin syringe (.5 ml) to boot!

Almost 2 decades ago as it took place from Jan-Dec 2002.

My urologist did another small pilot study in 2005.

He has been using subcutaneous testosterone injections on his patients since the mid-2000s.




Subcutaneous administration of testosterone A pilot study report (2006)


Objective:
To investigate the effect of low doses of subcutaneous testosterone in hypogonadal men since the intramuscular route, which is the most widely used form of testosterone replacement therapy is inconvenient to many patients.

Methods: All men with primary and secondary hypogonadism attending the reproductive endocrine clinic at Royal Victoria Hospital, Montreal, Quebec, Canada, were invited to participate in the study. Subjects were enrolled from January 2002 till December 2002. Patients were asked to self-administer weekly low doses of testosterone enanthate using a 0.5 ml insulin syringe.

Results:
A total of 22 patients were enrolled in the study. The mean trough was 14.48 ± 3.14 nmol/L and the peak total testosterone was 21.65 ± 7.32 nmol/L. For the free testosterone, the average trough was 59.94±20.60 pmol/L and the peak was 85.17 ± 32.88 pmol/L. All of the patients delivered testosterone with ease and no local reactions were reported.

Conclusion: Therapy with weekly subcutaneous testosterone produced serum levels that were within the normal range in 100% of patients for both peak and trough levels. This is the first report, which demonstrated the efficacy of delivering weekly testosterone using this cheap, safe, and less painful subcutaneous route.



Keep in mind that the peak and trough levels for both free and total testosterone were taken a day before and a day after the injection.



Methods. Twenty-two patients with hypogonadism (primary and secondary) were enrolled from the reproductive endocrine clinic in the Royal Victoria Hospital, Montreal, Quebec, Canada. Subjects were selected from January 2002 to December 2002. Prior to starting testosterone therapy, initial blood was taken for baseline total testosterone and free testosterone. Total testosterone was measured using Advia Centaur assay (Bayer Corporation). This assay is a competitive immunoassay using direct chemiluminescent technology. The total percent coefficient of variation (CV) for this test is 5%. CoatA-Count (Diagnostic Products Corporation, Los Angeles, CA) was used to measure free testosterone. This assay uses a solid-phase 125I radioimmunoassay designed for the quantitative measurement of free testosterone in serum with a coefficient of variation of 8%. Each patient was then educated on how to prepare testosterone injections. Testosterone enanthate in oil was used (Delatestryl, X Corp; 200mg/ml). The oily liquid was made less viscous by warming the bottle in the axilla for at least 5 minutes before injection. A microfine 0.5 ml insulin syringe (BectonDickensen, Chicago, IL, USA) was also warmed in the opposite axilla. The patient was then shown how to give testosterone injections subcutaneously into the abdomen. One week later a peak and trough levels for both free and total testosterone were taken a day before and a day after the injection. The starting dose of testosterone enanthate was 25-50 mg each week and then we adjusted according to the peak and trough levels and patient symptoms. The Hospital Ethics Committee granted institutional review board approval.

Results. A total of 22 hypogonadal men were enrolled in the study. The mean age was 33 ± 13 years with an age range of between 15 and 55 years. The mean subcutaneous weekly testosterone dose was 55 ± 27 mg with a minimum of 25 mg and a maximum of 100 mg. Age, hypogonadal diagnostic category, prior treatment regimen, and sex hormone levels are summarized in Table 1. Following initiation of treatment, the peak total and free testosterone levels were within the normal range both before (trough) and following injection (peak). The results are shown in Table 1 and Figures 1a and 1b. The mean total testosterone prior to injection was 14.5 ± 3.14 nmol/L and 21.7 ± 7.32 nmol/L the day following the injection. For the free testosterone, the mean trough level was 59.9 ± 20.6 pmol/L and the peak one day later was 85.2 ± 32.9 pmol/L. These results were within the normal male range for our laboratory (total testosterone10-38.5 nmol/L, and free testosterone 31.2-162.9 pmol/L). All the patients stated that subcutaneous injections were easy to use and well-tolerated. None of them reported any local reactions due to subcutaneous injections such as bruising, erythema, pain, swelling, and nodules. None discontinued using it.

* The mean total testosterone prior to injection was 14.5 ± 3.14 nmol/L and 21.7 ± 7.32 nmol/L the day following the injection. For the free testosterone, the mean trough level was 59.9 ± 20.6 pmol/L and the peak one day later was 85.2 ± 32.9 pmol/L.





Discussion.
In the current study, we demonstrated the efficacy of delivering subcutaneous testosterone using fine needle insulin syringes. Therapy with weekly subcutaneous testosterone produced levels that were within the normal range in 100% of patients for both peak and trough levels. Weekly testosterone injections thus resulted in much-reduced fluctuations in steroid hormone level and achieved normal circulating hormone levels. An earlier study reported using 100 mg of intramuscular testosterone once a week for 12 weeks in 12 men with primary hypogonadism.12 The mean serum testosterone concentration increased to slightly higher than the upper limit of normal 1-2 days after the injection and gradually decreased to the mid-normal range by the time of the next injection.12 In contrast, biweekly intramuscular treatment with 200 mg testosterone enanthate produced fluctuation in testosterone levels between the supraphysiological low-normal range.12-14 Regimens of 300 mg every 3 weeks and 400 mg every 4 weeks increased the peaks and decreased the nadir further.12 Subcutaneous testosterone injection was well tolerated by most patients and no local side effects were reported by any of the 22 patients. This eliminates the frequently reported local side effects caused by intramuscular injection such as local pain (7.4%), bleeding or bruising (15.2%), and coughing-fits or fainting possibly due to oil microembolization (1.5%).15 In conclusion, this is the first report on the use of subcutaneous testosterone administration, which with a new syringe, technology appeared to be a safe, inexpensive, and an effective form of treatment for hypogonadal men. Although the number of patients using subcutaneous testosterone was small, the overall clinical response was satisfactory. A large-scale study is needed to confirm these results. We foresee the production of a testosterone “pen” delivery system in the future.





I stated earlier this small pilot study was from 2002 and published in 2006.

Xyosted (testosterone enanthate) auto-injector for subcutaneous injection hit the market in 2018!

LOL!


* A large-scale study is needed to confirm these results. We foresee the production of a testosterone “pen” delivery system in the future.
 
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madman

Super Moderator
The small pilot study was done by my urologist in 2005.

It was posted up numerous times in 2006 and the years following on the numerous steroid forums when news first hit the scene along with the first pilot study ever done (Canada) using subcutaneous T injections. Subcutaneous administration of testosterone A pilot study report (2006) posted above.




STABLE TESTOSTERONE LEVELS ACHIEVED WITH SUBCUTANEOUS TESTOSTERONE INJECTIONS (2005)


Objectives:
The preferred technique of androgen replacement has been intramuscular (IM) testosterone, but wide variations in testosterone levels are often seen. Subcutaneous (SC) testosterone injection is a novel approach; however, its physiological effects are unclear. We, therefore, investigated the sustainability of stable testosterone levels using SC therapy.

Patients and methods:
Between May and September 2005, we conducted a small pilot study involving 10 male patients with symptomatic late-onset hypogonadism.

Every patient had been stable on TE 200 mg IM for 1 year. Patients were instructed to self-inject with testosterone enanthate (TE) 100 mg SC (DELATESTRYL 200 mg/cc, Theramed Corp, Canada) into the anterior abdomen once weekly. Some patients were down-titrated to 50 mg based on their total testosterone (T) at 4 weeks.

Informed consent was obtained as SC testosterone administration is not officially approved by Health Canada. T levels were measured before and 24 hours after injection during weeks 1, 2, 3, and 4, and 96 hours after injection in weeks 6 and 8.

At week 12, PSA, CBC, and T levels were measured however; the week 12 data are still being collected.

Results: Prior to initiation of SC therapy, T was 19.14+3.48 nmol/l, hemoglobin 15.8+1.3 g/dl, hematocrit 0.47+0.02, and PSA 1.05+0.65 ng/ml. During the first 4 weeks, there was a steady increase in pre-injection T from 19.14+3.48 to 23.89+9.15 nmol/l (p¼0.1). However, after 8 weeks the post-injection T (25.77+7.67 nmol/l) remained similar to that of week 1 (27.46+12.91 nmol/l). Patients tolerated this therapy with no adverse effects.

Conclusions: A once-week SC injection of 50-100 mg of TE appears to achieve sustainable and stable levels of physiological T. This technique offers fewer physician visits and the use of a smaller quantity of medication, thus lower costs. However, the long term clinical and physiological effects of this therapy need further evaluation.
 
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Cataceous

Super Moderator
... Testosterone enanthate in oil was used (Delatestryl, X Corp; 200mg/ml). ...

*
The mean total testosterone prior to injection was 14.5 ± 3.14 nmol/L and 21.7 ± 7.32 nmol/L the day following the injection. ...
Interestingly, this gives an apparent half-life of 10 days, just like XYOSTED. I see the preservative used is chlorobutanol, not benzyl alcohol.
 

Cataceous

Super Moderator
Can you explain what you said about that Xyosted has a half-life of 10 days???
Maybe you're aware that "half-life" is a measurement of how quickly a drug is used up in the body—how long it takes for half of the drug to be used up. The model it's based on assumes the rate of drug use is always directly proportional to the amount present. This makes the half-life constant, no matter how much drug is present. It's not a perfect model, but it is reasonably consistent with measured data.

The reason for my comment is that there's research and anecdotal data showing the half-lives for testosterone cypionate and testosterone enanthate to be more like five days. The question is, why do XYOSTED and Delatestryl have apparent half-lives that are twice as long? The clinical trial for XYOSTED I linked to above came up with a half-life of 239 hours, comparable to a calculation based on the Delatestryl data. A possible contributing factor is that unlike XYOSTED and Delatestryl, most testosterone formulations contain benzyl alcohol as a preservative, which is known to speed absorption, and therefore reduce the half-lives. I don't know if this is the whole story.
 

Justy

New Member
So, is it good that the Xyosted half-life is 10 days and I am injecting it every 7 days?

All of these are new to me so I'm learning and trying to understand...

Thx
 

madman

Super Moderator
So, is it good that the Xyosted half-life is 10 days and I am injecting it every 7 days?

All of these are new to me so I'm learning and trying to understand...

Thx

Regarding half-lives keep in mind that a majority of studies on the pharmacokinetics of the various T-esters were done using IM, not sub-q injections.

I would not get too caught up on the half-life between IM vs sub-q and you should have no issues injecting TE let alone TC sub-q once weekly as long as your trough TT level is in a healthy range and you feel well overall and are not experiencing any side-effects let alone blood markers are healthy!

The downfall may be if you were to run too high a trough level then your peak TT/FT let alone e2 will be higher which could cause issues for some.

Some men do well and prefer once-weekly injections using TE or TC (sub-q or IM).

Comes down to the individual and one's SHBG level can have a big impact on the protocol chosen.

Whether one chooses to inject once weekly, M/W/F, twice weekly (every 3.5 days), EOD, or daily the peak--->trough levels need to be kept in mind.

Depending on one where one SHBG sits some may feel better overall injecting more frequently which will not only clip the peak--->trough but blood levels will be more stable.




post#8

my reply to Systemlord:
Systemlord said:
SQ for me was a negative experience, the entire injection felt as though the Test converted straight to estrogen and days later it had felt like I missed a couple of injections.


Hope you understand that when injected sub-q the esterified T does not convert to E2 until the ester has been cleaved......which happens only when it enters the bloodstream and as stated below....."Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed"


"PRODRUG HYDROLYSIS WILL ONLY OCCUR IN BLOOD"



CONCLUSIONS


It is interesting to realize that drug absorption from an oil depot cannot entirely be described by a simple two-phase mass transfer model where concentration gradients, diffusion, and partition coefficients would enable the calculation of the expected absorption. It is demonstrated in this dissertation that there is a role of the excipient BOH in yielding an initially high absorption. The oil depot forms a continuous phase after injection but will be dispersed and encapsulated at the injection site after some days. This in turn largely influences the way the prodrug becomes available; after release from the oil depot, it is present in the interstitial fluid which is drained through the lymph into the systemic circulation. Subsequently, the prodrug permeates through the wall of blood cells and is hydrolyzed. Both the lymph transport and the cell wall permeation take time which is expressed in a lag time. This lag time is different for each injection site: a subcutaneously administered prodrug will enter the systemic circulation via a short path and at a low drainage flow. This results in a short lag time and a slow absorption rate constant of the prodrug. Deeper administered prodrugs (i.e. intramuscular injections) are suggested to be absorbed via a longer path, but at a higher flow, which results in a longer lag time but a higher absorption rate constant of the prodrug.


Screenshot (3157).png

Figure 7.2: Schematic overview of the new insights into drug absorption from oil depots. After release from the oil depot (yellow circle at the injection site), the prodrug is transferred towards the central compartment via the lymphatic system. Here, it will be hydrolyzed to the active substance (see circle). ka = absorption rate constant; ke = elimination rate constant.
 
Last edited:

madman

Super Moderator
If you want to take a deep dive go nuts!


 

Justy

New Member
If you want to take a deep dive go nuts!



It's a lot of information to digest.... I will be busy the whole week...

Thanks
 

Cataceous

Super Moderator
So, is it good that the Xyosted half-life is 10 days and I am injecting it every 7 days?
...
Yes, it is good, because it means less variation in testosterone over the course of each week. The traditional formulations with five-day half-lives can cause quite large swings with weekly injections; the peak levels can be two to three times the trough values.
 

Acer97

Member


Look over the Cavg/Cmax/Cmin (ng/dL) and Tmax (h)

Let alone the fluctuation (peak-to-trough) ratios (overall/various doses 50/75/100 mg)
View attachment 12379
Cavg 0–168h, average concentration over the 7-day dosing interval (0–168 hours); Cmax, maximum (peak) blood concentration; Cmin, minimum blood concentration; PK, pharmacokinetic; Tmax, time to reach maximum blood concentration; TT, total testosterone.

*The fluctuation (peak-to-trough) ratios were 1.813 for the overall study population and 1.854, 1.758, and 2.025 for the 50-, 75-, and 100-mg dose groups, respectively.





















Wtf the 50mg a week resulted in pretty much the same as 100mg a week?
 

Fortunate

Well-Known Member
Indeed, it looks like either ~8-12 hours post-injection for the first peak or ~36 hours post-injection for the second peak.
View attachment 12378
Is a double peak phenomenon, a common occurrence, or just something you see with Xyosted?
 
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